Hypercalcemia of malignancy occurs as the result of direct bone metastasis and via humoral mechanisms such as parathyroid hormone-related protein (PTHrP) or 1,25-dihydroxyvitamin D mediated pathways
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Hypercalcemia of malignancy and new treatment options - 0 views
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Hypercalcemia due to osteolytic bone lesions is common in multiple myeloma, leukemia, and breast cancer
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Humoral hypercalcemia is predominant in squamous cell, renal cell and ovarian cancers, and lymphomas are associated with 1,25-dihydroxyvitamin D mediated hypercalcemia
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20% of cases of hypercalcemia of malignancy and is frequently encountered in multiple myeloma, metastatic breast cancer, and to a lesser extent in leukemia and lymphoma
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Physiologic bone turnover requires the complementary activity of osteoblasts – mesenchymal stem cell-derived bone-forming cells – and bone-resorbing cells of monocyte and macrophage lineage known as osteoclasts
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In local osteolytic hypercalcemia, the RANKL/RANK interaction results in excessive osteoclast activation leading to enhanced bone resorption and thus hypercalcemia
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In addition, osteoclast activation is also mediated by malignancy secreted cytokines, including interleukin-1, initially termed “osteoclast stimulating factor”
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increased production of 1,25-dihydroxyvitamin D occurs nearly exclusively in Hodgkin and non-Hodgkin lymphoma with case reports of the same in ovarian dysgerminoma
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in 1,25-dihydroxyvitamin D induced hypercalcemia, malignant cells likely recruit and induce adjacent macrophages to express 1-α-hydroxylase, converting endogenous calcidiol into calcitriol.31 Calcitriol then binds to receptors in the intestine leading to heightened enteric calcium reabsorption with resultant hypercalcemia
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Ectopic production of PTH by malignant cells has been described in a handful of cases involving cancer of the ovary and lung, as well as neuroendocrine tumors and sarcoma
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an initial panel consisting of PTH, PTHrP, phosphorus, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D should be obtained
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Lymphoma, a hypercalcemia due to 1,25-dihydroxyvitamin D mediated pathways, is implied by elevations in 1,25-dihydroxyvitamin D without concomitant elevations in 25-hydroxyvitamin D. In such cases, PTH is low and PTHrP undetectable
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Treatment of hypercalcemia of malignancy is aimed at lowering the serum calcium concentration by targeting the underlying disease, specifically by inhibiting bone resorption, increasing urinary calcium excretion, and to a lesser extent by decreasing intestinal calcium absorption
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hydration with isotonic fluid (if admitted), avoidance of thiazide diuretics, and a low-calcium diet
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Does the Immune System Naturally Protect Against Cancer? - 0 views
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shared by Nathan Goodyear on 15 Jan 13
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Principles of innate and adaptive immunity - Immunobiology - NCBI Bookshelf - 0 views
www.ncbi.nlm.nih.gov/...NBK27090
immune system immune system innate immunity adaptive immunity humoral innate adaptive immunity
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shared by Nathan Goodyear on 19 Mar 14
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Immune Modulation in Multiple Sclerosis Patients Treated with the Pregnancy Hormone Est... - 0 views
www.jimmunol.org/...6267.long
MS RA rheumatoid arthritis psoriasis multiple sclerosis Estriol autoimmune disease inflammation hormone hormones E3
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A beneficial effect of pregnancy on clinical symptoms has been observed in MS and other Th1-mediated autoimmune diseases, including rheumatoid arthritis (RA), psoriasis, uveitis, and thyroiditis
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In general, Th1 lymphocytes secrete proinflammatory cytokines (e.g., IL-2, IL-12, IFN-γ, and TNF-α) that promote cellular immunity, while Th2 lymphocytes produce anti-inflammatory cytokines (e.g., IL-4, IL-5, IL-6, and IL-10) that promote humoral immunity
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Th2 cytokines are associated with the down-regulation of Th1 cytokines and may confer protection from Th1-mediated autoimmune diseases
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During pregnancy, there is a shift from Th1 to Th2 that occurs both locally, at the fetal maternal interface, (23, 24, 25), and systemically
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Gender and sex hormones in multiple sclerosis pathology and therapy - 0 views
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It is now well recognized that the disease manifestation is reduced in pregnant women with relapsing-remitting MS
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This occurs particularly during the third trimester when levels of estrogens (estradiol and estriol) and progesterone (see Table 2) are elevated up to about 20 times
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This clinical improvement is however followed by temporary rebound exacerbations at post-partum, when the hormone levels decline
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a shift from Th1 to Th2 immune response, expansion of suppressive regulatory T lymphocytes and decrease in the number of circulating CD16+ natural killer (NK)-cells
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Th1 lymphocytes secrete proinflammatory cytokines (e.g. IL-2, IFNgamma, lymphotoxin) while Th2 cells secrete anti-inflammatory cytokines (e.g. IL-4, IL-5, IL-10), which favor humoral-mediated responses
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Th2 cytokines are associated with down-regulation of Th1 cytokines and this Th2 shift is believed to provide protection from allograft rejection during pregnancy as well as from Th1-mediated autoimmune disease
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it is worth noting that the levels of other hormones with anti-inflammatory activity (1,25-dihydroxy-vitamin D3, norepinephrine, cortisol) also increase by 2 to 4 times during late pregnancy
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1,25-dihydroxy vitamin D3 induces regulatory T-cell function important for development of self-tolerance
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Leptin is a pleiotropic hormone produced primarily by adipocytes but also by T lymphocytes and neurons
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Several lines of evidence indicate that leptin contributes to EAE/MS pathogenesis, influencing its onset and clinical severity, by acting as a proinflammatory cytokine which promotes regulatory T cell (Treg) anergy and hyporesponsiveness, resulting in increased Th1 (TNFalpha, INFgamma) and reduced Th2 (IL-4) cytokine production
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circulating leptin levels are increased in relapsing-remitting MS patients (men and women analyzed together) while the CD4+CD25+Treg population decreases
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As the leptin plasma concentrations are proportional to the amount of fat tissue, obese/overweight individuals produce higher levels of leptin
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Nielsen et al found that estradiol and progesterone exert neuroprotection against glutamate neurotoxicity, while MPA antagonizes the neuroprotective effect of estradiol and exacerbated neuron death induced by glutamate excitotoxicity
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shared by Nathan Goodyear on 15 Apr 12
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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
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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
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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
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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.
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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
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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.
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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)
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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
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Furthermore, in response to progesterone, γδ T cells produce progesterone-induced blocking factor (PIBF) (54
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A defining characteristic of NK cells is their ability to lyse target cells without prior sensitization and without restriction by HLA antigens.
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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).
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The largest leukocyte population in the endometrium consists of NK cells named large granulated lymphocytes
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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)
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general proinflammatory effect of estrogen, causing an influx of macrophages and neutrophils, which is antagonized by progesterone through its receptor (70, 71).
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Through promotion of a uterine Th2 environment, progesterone could indirectly affect uNK cell function
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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
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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
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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
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Th1 immunity to trophoblast is associated with RPL, whereas Th2 immunity is associated with a successful pregnancy
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shared by Nathan Goodyear on 21 Dec 11
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Adipose Tissue Inflammation in Obesity and Metabolic Syndrome - - Satoshi Nishimura - D... - 0 views
www.discoverymedicine.com/...obesity-and-metabolic-syndrome
inflammation obesity metabolic syndrome fat adipose tissue innate immune system humoral
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Activation of inflammatory pathways in adipocytes impairs triglyceride storage and increases release of free fatty acids, an excess of which is known to induce insulin resistance in muscle and liver
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It has been postulated that a paracrine loop involving free fatty acids and inflammatory cytokines establishes a vicious cycle between adipocytes and macrophages that propagates the inflammation
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not only does interrupting the accumulation of macrophages within obese adipose tissue suppresses adipose inflammation in various animal models, it also ameliorates systemic insulin resistance and metabolic abnormalities, suggesting macrophages are key effector cells involved in adipose inflammation
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CD8+ T cells within obese adipose tissue induce activation and migration of monocytes/macrophages, and in cooperation with the adipose tissue, they also induce macrophage differentiation. At the same time, obese adipose tissue activates CD8+ T cells, creating a vicious cycle involving CD8+ T cells, macrophages, and obese adipose tissue that propagates local inflammation
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In obese adipose tissue there is a shift to dominance of CD8+ and TH1 T cells, which appears to propagate inflammation
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Psychological stress may induce increased humoral ... [Behav Med. 2000] - PubMed result - 1 views
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Molecular basis of cadmium toxicity. [Prog Food Nutr Sci. 1984] - PubMed result - 0 views
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Cadmium inhibits protein synthesis, carbohydrate metabolism and drug metabolizing enzymes in liver of animals.
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shared by Nathan Goodyear on 03 Dec 15
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Evaluation of candidal colonization and specific humoral responses against Candida albi... - 0 views
onlinelibrary.wiley.com/...abstract
candida candida albicans candidiasis yeast psoriasis dermatology
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shared by Nathan Goodyear on 16 Oct 18
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Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in ... - 0 views
www.ncbi.nlm.nih.gov/...PMC4560272
RIGVIR cancer oncolytic therapy immunotherapy cancer immunotherapy
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ECHO-7 virus strain, Picornaviridae family, Enterovirus genus, Enteric Cytopathic Human Orphan (ECHO) type 7, group IV, positive-sense single-stranded RNA virus
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a few side effects were reported, for example subfebrile temperature (37.5°C for a couple of days), pain in the tumour area, sleepiness and diarrhoea
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In this retrospective study, however, there was no record of any untoward side effect from Rigvir treatment or its discontinuation
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Early observations of tumour regressions after virus infections have been published starting from the late 19th century
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The present results show that in substage IB, IIA, IIB and IIC melanoma patients, Rigvir administration after surgery significantly (P<0.05) prolongs survival compared with patients who were managed according to current published guidelines
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no value higher than grade 2 was recorded in Rigvir-treated patients. This is in contrast to most other cancer therapies, where grades 3 and 4 are frequently observed
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Administration of virus induces the formation of neutralising antibodies that might potentially influence the efficiency of Rigvir
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In 94 healthy adult participants tested, the titres were found to be low (1 : 20 to 1 : 62) 39,40. When tested in 155 adult cancer patients who had not been treated with Rigvir, neutralising antibodies against ECHO-7 were detected in ∼50% of the patients
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the presence of ECHO-7 antibodies was shown to increase with age in children and level off to a plateau of around 75% in adults
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Rigvir is an immunomodulator that affects both the humoral, antibody-mediated, and the cellular immune systems
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it reduces the viability of melanoma, as well as pulmonary, gastric, pancreatic, bone, and breast cancer cell cultures
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Rare Occurrence of 3 "H": Hypercalcemia, Hemolytic Anemia and Hodgkin's Lymphoma - 0 views
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administered zoledronic acid (4 mg). Prednisolone (1 mg/kg/day) was started and simultaneously, she was administered first cycle of ABVD (Adriamycin: 25 mg/m2, Bleomycin: 10 U/m2, Vinblastine: 6 mg/m2 and Dacarbazine: 375 mg/m2), which led to normalisation of serum calcium levels over 4 days and improvement in her hemoglobin levels
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Etiology of anemia in Hodgkin’s lymphoma is multifactorial. Anemia of chronic disease, decreased red cell survival, infiltration of bone marrow by tumor and marrow suppression by chemotherapy/radiotherapy are the common mechanisms
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Our case had only a transient response to steroids and chemotherapy. Therefore, she was treated with Rituximab which brought hemolysis under control
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Hypercalcemia in HL is rare and its incidence has been reported as 0.9, 1.6 and 5.4 % in different series
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Hypercalcemia of malignancy involves three mechanisms: 1. Humoral hypercalcemia mediated by PTHrP—seen in solid tumors like breast cancer and adult T cell leukemia/lymphoma (ATLL), 2. Direct osteoclast mediated bone resorption due to bony metastasis—seen in solid tumors and multiple myeloma, 3. Calcitriol mediated hypercalcemia—seen in Hodgkin’s and non-Hodgkin’s lymphoma as well as granulomatous disorders like tuberculosis, sarcoidosis, leprosy and disseminated Candidiasis
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Mechanism of hypercalcemia in HL has long been suggested to involve extra-renal activation of 1α-hydroxylase leading to production of 1, 25(OD)2 Vitamin D3 or Calcitriol, an active metabolite of Vitamin D, which leads to increased re-absorption of calcium and phosphate from intestine, increased osteoclast activation and bone resorption as well as increased phosphate re-absorption in renal tubules
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The source of 1α-hydroxylase in HL has been postulated as monocytes and macrophages infiltrating the tumor akin to tuberculosis or sarcoidosis and is stimulated by IFN-γ secreted by T-lymphocytes
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Like sarcoidosis, patients with HL exhibit increased sensitivity to Vitamin D supplements and sunlight, which have been found to precipitate hypercalcemia in these patients
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Classical biochemical profile in Calcitriol mediated hypercalcemia include: an elevated calcium, normal/slightly elevated phosphate, normal 25(OH) Vitamin D, suppressed PTHrP and PTH, elevated Calcitriol and a normal/increased tubular reabsorption of phosphate
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not been associated with a poorer prognosis and tends to subside after treatment of the underlying disease
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Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside - 0 views
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MAF precursor activity has also been lost or reduced after Gc-globulin treatment in some cancer cell lines
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This appears to result from the deglycosylated ɑ-N-acetylgalactosaminidase (nagalase) secreted from cancerous cells
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Studies have shown that the production of nagalase has a mutual relationship with Gc-MAF level and immunosuppression
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It has been demonstrated that serum levels of nagalase are good prognosticators of some types of cancer
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The nagalase level in serum correlates with tumor burden and it has been shown that Gc-MAF therapy progresses, nagalase activity decreases
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It has been shown that Gc-MAF can inhibit the angiogenesis induced by pro-inflammatory prostaglandin E1
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The effect of Gc-MAF on chemotaxis or activation of tumoricidal macrophages is likely the main mechanism against angiogenesis.
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Administration of Gc-MAF stimulates immune-cell progenitors for extensive mitogenesis, activates macrophages and produces antibodies. “This indicates that Gc-MAF is a powerful adjuvant for immunization.”
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Cancer cell lines do not develop into tumor genes in mouse models after Gc-MAF-primed immunization (29-31) and the effect of Gc-MAF has been approved for macrophage stimulation for angiogenesis, proliferation, migration and metastatic inhibition on tumors induced by MCF-7 human breast cancer cell line
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The protocol included: "a high dose of second-generation Gc-MAF (0.5 ml) administered twice a week intramuscularly for a total of 21 injections.”
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Yamamoto et al. showed that the administration of Gc-MAF to 16 patients with prostate cancer led to improvements in all patients without recurrence
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Inui et al. reported that a 74-year-old man diagnosed with prostate cancer with multiple bone metastases was in complete remission nine months after initiation of GcMAF therapy simultaneously with hyper T/NK cell, high-dose vitamin C and alpha lipoic acid therapy
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It has also been approved for non-neoplastic diseases such as autism (41), multiple sclerosis (42, 43), chronic fatigue syndrome (CFS) (40), juvenile osteoporosis (44) and systemic lupus erythematous (45).
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Gc-MAF has been verified for use in colon, thyroid (38), lung (39), liver, thymus (36), pancreatic (40), bladder and ovarian cancer and tongue squamous carcinoma
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Prostate, breast, colon, liver, stomach, lung (including mesothelioma), kidney, bladder, uterus, ovarian, head/neck and brain cancers, fibrosarcomas and melanomas are the types of cancer tested thus far
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weekly administration of 100 ng Gc-MAF to cancer at different stages and types showed curative effects at different follow-up times
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Studies have shown that weekly administration of 100 ng Gc-MAF to cancer patients had curative effects on a variety of cancers
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Because the half-life of the activated macrophages is approximately one week, it must be administered weekly
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In vivo weekly intramuscular administration of Gc-MAF (100 ng) for 16-22 weeks was used to treat patients with breast cancer
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individuals harboring different VDR genotypes had different responses to Gc-MAF and that some genotypes were more responsive than others
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Administration of Gc-MAF for cancer patients exclusively activates macrophages as an important cell in adaptive immunity
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Gc-MAF supports humoral immunity by producing, developing and releasing large quantities of antibodies against cancer. Clinical evidence from a human model of breast cancer patients supports this hypothesis
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It is likely that the best therapeutic responses will be observed when the nutritional and inflammatory aspects are taken together with stimulation of the immune system
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it should be noted that no harmful side effects of Gc-MAF treatment have been reported, even when it was successfully administered to autistic children
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The natural activation mechanism of macrophages by Gc-MAF is so natural and it should not have any side effects on humans or animal models even in cell culture
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Besides the Gc-MAF efficacy on macrophage activity, it can be a potential anti-angiogenic agent (28) and an inhibitor of the migration of cancerous cells in the absence of macrophages (47).
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Activating or modifying natural killer cells, dendritic cells, DC, CTL, INF and IL-2 have all been recommended for cancer immunotherapy
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It has been reported that nagalase cannot deglycosylate Gc-MAF as it has specificity for Gc globulin alone
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inflammation-derived macrophage activation with the participation of B and T lymphocytes is the main mechanism
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Previous clinical investigations have confirmed the efficacy of Gc-MAF. In addition to activating existing macrophages, Gc-MAF is a potent mitogenic factor that can stimulate the myeloid progenitor cells to increase systemic macrophage cell counts by 40-fold in four days
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Evidence for Aerosol Transfer of SARS-CoV-2-Specific Humoral Immunity | ImmunoHorizons ... - 0 views
Autoantibodies in COVID‐19 correlate with antiviral humoral responses and dis... - 0 views
www.ncbi.nlm.nih.gov/...PMC9111424
COVID-19 NETosis ANA autoimmune covid19 COVID IL-6 NETs SARS-CoV-2
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