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Nathan Goodyear

Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Amo... - 0 views

  • Heat exposure (40 °C to 43 °C) of cancer cells in preclinical studies, and hyperthermia regionally applied to patients in early randomized clinical studies, have shown synergistic activity with ionizing radiation and chemotherapy
  • For the combination of hyperthermia with chemotherapy, the study group at Munich7 was the first to demonstrate the safety and efficacy of regional hyperthermia (RHT) in patients with high-risk sarcoma.
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    hyperthermia therapy augments chemo therapy.
Nathan Goodyear

Effects of Angiotensin, Vasopressin and Aldosterone on Proliferation of MCF-7 Cells and... - 0 views

  • The renin-angiotensin system (RAS) has been associated with local tumor growth, inflammation, angiogenesis and facilitation of metastasis
  • Aldosterone and vasopressin did not alter cellular growth (Figure 1) and did not alter doxorubicin sensitivity
  • angiotensin increased the growth of MCF-7 cells
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  • losartan
  • evidence that breast cancer chemotherapy can be influenced by anti-hypertensive treatment
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    upregulated RAS associated with stimulated breast cancer growth.  Anti-hypertensive therapy not only can it impact the cancer growth potential but also can augment chemotherapy.
Nathan Goodyear

Hypercalcemia of malignancy and new treatment options - 0 views

  • 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
  • ectopic secretion of parathyroid hormone (PTH) has been implicated
  • 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
  • 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
  • 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
  • In local osteolytic hypercalcemia, the RANKL/RANK interaction results in excessive osteoclast activation leading to enhanced bone resorption and thus hypercalcemia
  • In addition, osteoclast activation is also mediated by malignancy secreted cytokines, including interleukin-1, initially termed “osteoclast stimulating factor”
  • Macrophage inflammation protein 1-alpha (MIP 1-alpha)
  • hypercalcemia is through extra-renal 1,25-dihydroxyvitamin D (calcitriol) production
  • 1% of cases
  • 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
  • 1-α-hydroxylase in the kidney, a process regulated by PTH
  • 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
  • this mechanism of disease is best conceptualized as an absorptive form of hypercalcemia
  • 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
  • primary hyperparathyroidism and malignancy comprising nearly 90% of cases of hypercalcemia
  • an initial panel consisting of PTH, PTHrP, phosphorus, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D should be obtained
  • 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
  • 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
  • mildly symptomatic disease
  • marked symptoms
  • hydration with isotonic fluid (if admitted), avoidance of thiazide diuretics, and a low-calcium diet
  • denosumab
  • Denosumab is an RANKL antibody that inhibits osteoclast maturation, activation, and function
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    hypercalcemia in cancer and treatments.
Nathan Goodyear

From the Cyclooxygenase-2 Inhibitor Celecoxib to a Novel Class of 3-Phosphoinositide-De... - 0 views

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    Celebrex useful in reducing colorectal polyps in individuals with familial adenomatous polyposis and in the treatment of cancer via induction of apoptosis and decrease in metastatic potential.
Nathan Goodyear

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor,... - 0 views

  • the MAF precursor activity of prostate cancer patient Gc protein is lost or reduced, because their serum Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells
  • Administration of 100 ng of GcMAF
  • 100 ng of GcMAF was administered intramuscularly once a week
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  • As GcMAF therapy progressed the MAF precursor activity of all five patients increased and their serum Nagalase activity decreased inversely
  • As GcMAF therapy progressed, the MAF precursor activity increased with a concomitant decrease in serum Nagalase activity
  • serum Nagalase is proportional to tumor burden
  • as GcMAF therapy progressed, serum Nagalase activity decreased and, concomitantly, tumor burden decreased
  • the serum Nagalase activities of all 16 patients decreased as GcMAF therapy progressed
  • annual computed tomographic scans of these patients confirmed them being tumor recurrence-free for the 7 years
  • undifferentiated cells were killed rapidly during the first few weeks, and the differentiated cells were killed slowly in the remaining GcMAF therapeutic period
  • PSA levels of prostatectomized patients decreased as serum Nagalase decreased during GcMAF therapy
  • In patients without tumor resection, however, although serum Nagalase activity decreased as GcMAF therapy progressed, their PSA values remained unchanged. The result suggests that the PSA derived from tumor-bearing prostate did not change while tumor burden decreased. Because tumor-induced inflammation in the noncancerous prostate tissues causes secretion of PSA [38], the PSA produced from these inflamed noncancerous prostate tissues cannot be changed by the decrease in tumor burden
  • Advanced cancer patients have high serum Nagalase activities, resulting in no macrophage activation and severe immunosuppression that explain why cancer patients die with overwhelming infection
  • Prognostic utility of serum α-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients
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    GC-MAF levels exist in inverse relationship to nagalase.  In this study of men with prostate cancer, weekly GCMAF injections reduced Nagalase activity to levels found in healthy controls suggesting tumor free. The dose was 100 ng/week. Nagalase is a protein that suppresses GC-MAF production and thus is immunosuppressive.
Nathan Goodyear

Comparisons of normal saline and lactated Ringer's resuscitation on hemodynamics, metab... - 0 views

  • NS contains 154 mM Na+ and Cl-, with an average pH of 5.0 and osmolarity of 308 mOsm/L.
  • LR solution has an average pH of 6.5, is hypo-osmolar (272 mOsm/L), and has similar electrolytes (130 mM Na+, 109 mM Cl-, 28 mM lactate, etc.) to plasma
  • hyperchloremic acidosis
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  • LR’s acid base balance is superior to that of NS’s
  • There were no significant differences between LR and NS groups in fibrinogen concentrations or platelet count
  • Total protein dropped
  • no significant differences in Hct (Table  1) or total protein between LR and NS groups
  • Bicarbonate HCO3- levels were decreased by hemorrhage but returned to pre-hemorrhage values by 3 h after LR resuscitation, whereas no return was observed with NS resuscitation
  • Na+ was increased after NS resuscitation
  • No changes in Na+ or K+ were observed
  • K+ did not change initially after NS resuscitation but was elevated at 6 h afterwards
  • Ca++ was similarly decreased
  • Cl- was elevated for 6 h after NS resuscitation, with no changes shown after LR resuscitation
  • PT was similarly prolonged by resuscitation with LR (from 11.2 ± 0.2 sec at baseline to 12.1 ± 0.2 sec at 6 h) and NS
  • Plasma aPTT was also similarly prolonged by resuscitation with LR (from 17.1 ± 0.5 sec baseline to 20.1 ± 1.2 sec at 6 h) or NS
  • NS resuscitation resulted in better oxygen delivery and oxygen delivery-to-oxygen demand ratio as an index of oxygen debt
  • NS had better tissue perfusion and oxygen metabolism than LR
  • LR resuscitation returned BE and bicarbonate to pre-hemorrhage levels within 3 h, but no return of BE or bicarbonate was observed for 6 hr with NS resuscitation
  • current blood bank guidelines state that LR should not be mixed with blood to prevent the risk of clot formation from calcium included in LR
  • LR resuscitation should not be given with blood through the same iv-line and crystalloids should be avoided in patients with blood transfusion
  • PT and aPTT were prolonged for 6 h after hemorrhage and resuscitation, suggesting a hypocoagulable states
  • potential thrombotic risk from LR resuscitation is unlikely.
  • we suspected that the blood pressure after NS resuscitation would be lower than that of LR due to its vasodilator effects
  • NS required a larger resuscitation volume and was associated with poor acid base status and elevated serum potassium in this model
  • NS required 50% more volume and was associated with a higher cardiac output and lower peripheral resistance, as compared to LR resuscitation
  • These differences are possibly due to the vasodilator effects from NS
  • an elevation of K+ was observed at 6 h post NS resuscitation, while no change of K+ was observed after LR resuscitation
  • The mechanism for the increase of K+ from NS is not fully known
  • NS is associated with vasodilator effects and the risks of metabolic acidosis and hyperkalemia
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    LR vs NS crystalloid.
Nathan Goodyear

The role of vitamin C in the treatment of pain: new insights - 0 views

  • recommended that during illness one should be careful about the intake of vitamin C, keeping in mind that acute illness rapidly depletes stores of ascorbic acid
  • it is possible that other hospital-associated pain may be partly due to vitamin C deficiency, which is relatively prevalent in hospital settings
  • Vitamin C deficiency (defined as plasma vitamin C concentrations <11 µmol/L
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  • Vitamin C is cost effective and appears to be a safe and effective adjunctive therapy for specific pain relief
  • it decreases the requirement for opioid analgesics, particularly post surgically and for bone metastasis
  • recent research has indicated a positive impact of high dose vitamin C on cancer- and chemotherapy-related quality of life, including pain
  • Cameron and Campbell [81] reported a number of cases of dramatic to complete amelioration of bone pain in patients with severe cancer-related pain given both high dose oral and intravenous vitamin C
  • hypovitaminosis C (defined as plasma vitamin C concentrations <23 µmol/L
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    vitamin C reduces pain; mechanism of action likely anti-inflammatory antioxidant, but yet inconclusive.
Nathan Goodyear

Genetic Determinants of Serum Testosterone Concentrations in Men - 0 views

  • mean serum testosterone concentrations were found to be lower in men with GG than in those with TT genotype for rs12150660
  • men with the CT genotype for rs6258 had lower serum testosterone concentrations than those with CC genotype.
  • The two autosomal SNPs identified by GWAS had a significant influence on the risk of having low serum testosterone (serum testosterone <300 ng/dl) in both the discovery and the replication cohorts with a combined odds ratio (OR) per minor allele of 0.72 (95% CI, 0.65 – 0.79) and 2.7 (95% CI, 2.1 – 3.5) for rs12150660 and rs6258, respectively
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  • The risk of having low serum testosterone concentrations increased by the number of risk alleles with an OR of 1.62 (95% CI, 1.41 – 1.86) for each risk allele (Figure S4). Low serum testosterone concentrations were 6.5-times more prevalent in men with ≥3 risk alleles (30.1% prevalence of low serum testosterone) compared to men without any risk allele (4.6% prevalence of low serum testosterone;
  • SNP rs5934505 was associated with serum testosterone without SHBG-adjustment (combined p-value of 1.7×10−9) and with free testosterone (combined p-value of 6.7×10−15), but not with SHBG
  • The mean serum testosterone and calculated free testosterone but not SHBG concentrations were lower in men with T genotype than in those with C genotype for rs5934505
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    Genetic SNP rs5934505 associated with lower total Testosterone and lower calculated free Testosterone.  No effects on SHBG.
Nathan Goodyear

SAGE Journals: Your gateway to world-class journal research - 0 views

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    Quercetin found to inhibit HSP 70 which also delayed HSP 90 transcription. HSPs are increased in response to thermal stress. This results in an anti-apoptosis effect and increased cell survival
Nathan Goodyear

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

  • 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
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  • 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)
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    Study finds benefit of PET scan in prognosis in ER+/HER2- breast cancers.
FMS Dental Hospital

Best Cosmetic Dental Clinic in India - 0 views

FMS DENTAL is one of the top dental clinics in Hyderabad, India and 5th best dental center in the world (GCR Rating), with multi-specialty practice, in-patient facility and 24 hr. emergency dental ...

Best Cosmetic Dental Clinic in India Dentist

started by FMS Dental Hospital on 27 Mar 18 no follow-up yet
Nathan Goodyear

IL-2: The First Effective Immunotherapy for Human Cancer | The Journal of Immunology - 0 views

  • IL-2 is a 15.5-kDa cytokine secreted predominately by Ag-simulated CD4+ T cells, but it can also be produced by CD8+ cells, NK cells, and activated dendritic cells
  • IL-2 is the predominant factor responsible for the maintenance of CD4+ regulatory T cells
  • A generalized capillary leak syndrome was induced by IL-2 in vivo that resulted in interstitial pulmonary infiltrates and substantial weight gain in patients
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  • The side effects were transient and returned to baseline following treatment
  • Tumors do not express IL-2 receptors and thus the antitumor activity was the result of IL-2 stimulation of immune cell
  • Patients with metastatic melanoma or metastatic renal cell cancer were uniquely responsive to high-dose IL-2 administration, and except for patients with advanced non-Hodgkin’s lymphomas (35) only rare responses were seen in patients with other tumor types
  • The underlying toxicity of IL-2 results from a capillary leak that leads to fluid extravasation into visceral organs that can compromise their function
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    Great review of the history of IL-2 in the treatment of cancer.  IL-2 stimulates the immune system to attack cancer.  Don't reinvent the wheel; use what is already present and available.
Nathan Goodyear

Anticancer Effects of Niclosamide in Human Glioblastoma | Clinical Cancer Research - 0 views

  • glioblastoma remains a fatal disease with a median overall survival time of only 15 months
  • inter- and intrapatient tumor heterogeneity
  • cellular and genetic diversity that characterizes glioblastoma
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  • This broad effect could be a result of niclosamide's pleiotropic activity, similarly affecting signaling pathways that are known to be overly active in human malignant cells (i.e., mTOR, NOTCH, WNT/CTNNB1; refs. 44–46)
  • It is a salicylanilide that was introduced as a molluscide in 1959
  • Studies in animals suggested no mutagenic, oncogenic, or embryotoxic activity and no cumulative effects
  • its rate of absorption from the intestinal tract was estimated at only 33%
  • the potential mechanism of synergy between temozolomide and niclosamide as a “natural inducer” of NFKBIA
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    Niclosamide pilot animal study useful in the treatment of Glioblastoma.  Found to inhibit NOTCH, mTOR, and WNT and cancer signaling. Also found to reduce the malignant potential through cytostatic, cytotoxic and antimigratory effects of niclosamide on GBM
Nathan Goodyear

Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem C... - 0 views

  • Here, we report on niclosamide as an antileukemic agent with two independent antineoplastic mechanisms: NF-κB pathway inactivation and ROS generation
  • In this report, we validated the inhibitory action of niclosamide against tumor necrosis factor (TNF)–induced NF-κB activation in AML cells and identified its mechanism, together with generation of reactive oxygen species (ROS), as being responsible for induced apoptosis of AML cells
  • NF-κB plays a critical role in inflammation, antiapoptotic responses, and carcinogenesis
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  • pharmacologic inhibition of NF-κB was effective in killing AML cells
  • High NF-κB expression is found in primitive human AML blast cells
  • niclosamide inhibited the TNF-induced NF-κB reporter activity in a dose- and time-dependent manner
  • niclosamide inhibiting TNF-induced IKK phosphorylation (Fig. 2A), niclosamide may exert its inhibitory effect at the TAK1 step
  • Pretreatment with niclosamide completely blocked the time- and dose-dependent TNFα-induced alteration of the NF-κB–DNA complex
  • niclosamide inhibited constitutively active NF-κB binding to DNA in U266 cells
  • niclosamide completely abolished the TNFα-induced phosphorylation of IKKα/β and IκBα
  • Accordingly, the TNFα-induced degradation of IκBα was abrogated by niclosamide
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    Old anti-parasitic medication, niclosamide, found to have anti-leukemic acitivty through inactivation of NF-kappaB and increase in ROS production in in Vitro and in Vivo study.
Nathan Goodyear

Medical education in pharmacogenomics-results from a survey on pharmacogenetic knowledg... - 0 views

  • Of participants, 84.3% found pharmacogenomics relevant to their current practice
  • More than two-thirds (65.7%) did not order nor recommend a pharmacogenomic test in the past year
  • pharmacogenomic testing was understood mainly for assessment of the variability of genes affecting drug disposition, metabolism and drug transport leading to individual responses to drugs
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  • Pre-emptive, prospective, genotyping to make individualised drug therapy feasible is seen to contribute to personalised medicine
  • assumed to improve drug efficacy and safety
  • Potential benefits of pharmacogenomics (PGx) have been defined such as predicting intended response to medication by more accurate dosing, avoiding adverse drug reactions and therefore enhancing drug safety and reducing health care cost
  • survey among Dutch pharmacists revealed 14.7% recent users of PGx diagnostics [27], whereas in our cohort, the percentage was with 34.3% higher.
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    Doctors and pharmacists are slow to integrate pharmacogenetics. Good working definition of pharmacogenetics as well.
Nathan Goodyear

Immune responses to malignancies - 0 views

  • increased densities of T-cell infiltrates with a high proportion of CD8+ T cells within primary colorectal carcinomas were associated with a significant protection against tumor recurrence
  • coexpression of genes mediating cytotoxicity and TH1 adaptive immune responses accurately predicted survival in patients with colorectal carcinoma independently of the metastatic status.
  • tumor-specific cytolytic T lymphocytes (CTLs)
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  • tumor-associated antigens (TAs)
  • Proinflammatory cytokines secreted by inflammatory cells can contribute to tumor progression, and soluble factors produced by the tumor in response to nonspecific or tumor-specific signals, such as prostaglandin E2 (PGE2), adenosine, or TGF-β, downregulate functions of immune cells
  • they are largely ineffective in arresting tumor growth, although they can proliferate and mediate antitumor cytotoxicity on their removal from the tumor bed and ex vivo IL-2 activation.42
  • DCs (HLA-DR+CD86+CD80+CD14−) are nature’s best APCs
  • They are a common component of tumor immune infiltrates and are responsible for the uptake, processing, and cross-presentation of TAs to naive or memory T cells, thus playing a crucial role in the generation of tumor-specific effector T cells
  • DCs control the induction of Treg cells. In patients with cancer, cellular interactions between antigen-presenting DCs and T cells lead to expansion and accumulation of Treg cells at the tumor site and in the periphery
  • NK cells (CD3−CD56+CD16+), which mediate innate immunity and contain both perforin-rich and granzyme-rich granules, are well equipped to mediate lysis of tumor cells
  • B cells (CD19+, CD20+) are also rare in most human tumors, with the exception of breast cancer and melanoma
  • The initial acute inflammation involving the recruitment and influx of antitumor effector cells is replaced by chronic inflammation in later stages of tumor progression
  • Tissue hypoxia plays a major role in shaping the nature of immune infiltrates in tumors
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    Another great review of the immune system during different stages of carcinogenesis; how the cancer manipulates the immue system to cloak itself from the immune system.
Nathan Goodyear

Cutting Edge: IL-12 Induces CD4+CD25− T Cell Activation in the Presence of T ... - 0 views

  • Whereas IL-12 instigates Th1 immune responses, CD4+CD25+ regulatory T cells (Treg)3 actively restrain them
  • Following engagement of their TCR, Treg suppress the proliferation of conventional CD4+CD25− T responder cells in vitro
  • Furthermore, they inhibit the development of CD4+ T cell responses against alloantigens, tumor, microbial, and self-Ags in vivo.
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  • Treg act to prevent spontaneous autoimmunity and to limit collateral damage to healthy tissues during adaptive immunity. However, these cells also have the potential to sabotage protective antimicrobial responses
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    Great T cell activiation review: Il-2 stimulates NK cells primarily release from TH1 cells and T cytotoxic lymphocytes are under the control of IL-12 released primarily from dendritic cells.  Inflammatory cytokines in the presence of Treg to stimulate CD4+CD25- T cell activation.
Nathan Goodyear

Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L Preparations - 0 views

  • Among the most encouraging mAb is trastuzumab, which targets the human epidermal growth factor receptor 2 and is indicated in the treatment of breast cancer
  • bevacizumab, which inhibits vascular endothelial growth factor and is indicated in the treatment of a range of diseases, including colorectal, lung, and ovarian cancer3; and cetuximab, which blocks the epidermal growth factor receptor and is indicated in the treatment of colorectal and lung cancer
  • Viscum album L (VA or European mistletoe) preparations are widely used as additive cancer therapy in Europe, especially in German-speaking countries, and have been associated with a reduction in chemotherapy-related adverse drug reactions and increased HRQL
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  • leading to enhancement of interleukin-12 secretion and natural killer cell function
  • Helixor VA preparations
  • A multivariable GEE model indicated that the odds for patients experiencing an AE following mAb therapy were nearly 5 times higher compared with that for mAb plus VA
  • VA preparations (Iscador Ltd) did not inhibit chemotherapy-induced cytostasis or cytotoxicity and showed an additive inhibitory effect at higher concentrations of VA.
  • previous in vitro investigations have shown that VA preparations have either no or minor effects on a range of CYPs, suggesting that VA-drug interactions based on drug metabolism are unlikely
  • mAb do not undergo hepatic metabolism but undergo proteolytic catabolism throughout the body
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    VAE therapy found to reduce adverse events in those receiving monoclonal Ab therapy.
markfletcher

Prominent Yoga Poses You Must Do During Pregnancy To Have A Normal Delivery - 0 views

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    What happens during a typical prenatal yoga class?
Nathan Goodyear

Clinical experience with intravenous administration of ascorbic acid: achievable levels... - 0 views

  • Patients with higher tumor markers are likely to have higher tumor burden, higher oxidative stress and, therefore, are more likely to have lower post IVC plasma levels.
  • Our data also showed that cancer patients with metastasis tend to have lower post-IVC vitamin C levels than those without metastasis
  • Lower peak plasma concentrations are obtained in cancer patients than in healthy subjects. Cancer patients who are deficient in vitamin C prior to therapy tend to achieve lower plasma levels post infusion.
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  • Patients with higher inflammation or tumor burdens, as measured by CRP levels or tumor antigen levels, tend to show lower peak plasma ascorbate levels after IVC.
  • Patients with metastatic tumors tend to achieve lower post infusion plasma ascorbate levels than those with localized tumors.
  • The inflammatory microenvironment of cancer cells leads to increasing oxidative stress, which apparently depletes vitamin C, resulting in lower plasma ascorbate concentrations in blood samples post IVC infusion. Another explanation for this finding may be that cancers are themselves more metabolically active in their uptake of vitamin C, causing subjects to absorb more of the vitamin, and as a results show lower plasma ascorbate concentrations in blood post IVC infusion.
  • Most of the prostate cancer patients studied, 75±19% (95% confidence), showed reductions in PSA levels during the course of their IVC therapy
  • Laboratory studies suggest that, at high concentrations, ascorbate does not interfere with chemotherapy or irradiation and may enhance efficacy in some situations
  • Cameron and Pauling observed fourfold survival times in terminal cancer patients treated with intravenous ascorbate infusions followed by oral supplementation
  • Meta-analyses of clinical studies involving cancer and vitamins also conclude that antioxidant supplementation does not interfere with the efficacy of chemotherapeutic regiments
  • patients with severely elevated CRP levels attain plasma ascorbate concentrations after IVC infusions that are only 65% of those attained for subjects with normal CRP levels
  • The finding of decreased plasma ascorbate levels in cancer patients may relate to the molecular structure of ascorbic acid; in particular, the similarity of its oxidized form, dihydroascorbic acid, to glucose
  • Since tumor have increased requirement for glucose [67], transport of dehydroascorbate into the cancer cells via glucose transport molecules and ascorbate through sodium-dependent transporter may be elevated
  • Increased accumulation of ascorbic acid in the tumor site was supported by measurements of the level of ascorbic acid in tumors in animal experiments
  • Regarding inflammation, 73±13% of subjects (95% confidence) showed a reduction in CRP levels during therapy. This was an even more dramatic 86±13% (95% confidence) in subjects who started therapy with CRP levels above 10 mg/L
  • IVC therapy appears to reduce CRP levels in cancer patients.
  • CRP concentrations directly correlate with disease activity in many cases and can contribute to disease progression through a range of pro-inflammatory properties.
  • Being an exquisitely sensitive marker of systemic inflammation and tissue damage, CRP is very useful in screening for organic disease and monitoring treatment responses
  • ncreases in CRP concentrations have been associated with poorer prognosis of survival in cancer patients, particularly with advance disease independent of tumor stage
  • patients with advanced malignancies may have lower level of ascorbic acid in tissue, creating a higher demand for the vitamin C
  • patients treated by IVC with follow-up several year showed that suppression of inflammation in cancer patients by high-dose IVC is feasible and potentially beneficial
  • Inflammation is a marker of high cancer risk, and poor treatment outcome
  • The subjects with highly elevated CRP concentrations have a three-fold elevation “all-cause” mortality risk and a twenty-eight fold increase in cancer mortality risk
  • cancer patients may need higher doses to achieve a given plasma concentration.
  • patients with lower vitamin C levels may see more distribution of intravenously administered ascorbate into tissues and thus attain less in plasma.
  • When treating patients with IVC, the first treatment likely serves to replenish depleted tissue stores, if those subjects were vitamin C deficient at the beginning of the treatment. Then, in subsequent treatments, with increasing doses, higher plasma concentrations can be attained. On-going treatments serve to progressively reduce oxidative stress in cancer patients.
  • large doses given intravenously may result in maximum plasma concentrations of roughly 30 mM, a level that has been shown to be sufficient for preferential cytotoxicity against cancer cells
  • oral intake of vitamin C exceeded 200 mg administered once daily, it was difficult to increase plasma and tissue concentrations above roughly 200 μM.
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    Great review on the use of IV vitamin C in cancer and to reduce inflammation.  The article does a great job of discussing the mechanism of vitamin C therapy in cancer as well as the proposed reasons for low vitamin C in cancer patients.  The study also highlights the obstacles to rise in vitamin C levels post IV vitamin C in cancer patients.
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