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Our data also suggest that 30-day mortality might be higher than previously estimated by several clinical trials.9, 10 The 30-day mortality rate after SACT with curative intent for NSCLC reported here is high at 3% compared with published trial data for the standard treatments, which suggested that 0·8% of patients died from treatment-induced toxicity when chemotherapy was given as adjuvant treatment alongside surgery

findings of clinical trials in selected age cohorts cannot readily be generalised to all patients

Chen et al. have revealed that ascorbate at pharmacologic concentrations (0.3–20 mM) achieved only by intravenously (i.v.) administration selectively kills a variety of cancer cell lines in vitro, but has little cytotoxic effect on normal cells.

Ascorbic acid (the reduced form of vitamin C) is specifically transported into cells by sodium-dependent vitamin C transporters (SVCTs)

SVCT-1 is predominantly expressed in epithelial tissues

Vitamin C alone at concentrations up to 57 μM had little effect on cell growth but was toxic at 228 μM (SI Appendix, Fig. S1B), in line with recent studies of high vitamin C concentrations (125–2,000 μM)

In our combination approach, vitamin C increased the effects of low doses of 5-aza-CdR, with 57 μM vitamin C almost doubling the growth inhibition

Using the Chou–Talalay method (28), we found that the two compounds indeed acted synergistically, rather than additively, to inhibit cancer cell growth over the physiological ranges of vitamin C in healthy individuals (26–84 μM)

HERVs have been inherited by successive generations and it is possible that some have conferred biological benefits

However, several HERVs have been implicated in certain cancers and autoimmune diseases

HERVs constitute about 1% of the human genome

The SOC for GBM was modified in this patient to initiate KMT prior to surgical resection, to eliminate steroid medication, and to include HBOT as part of the therapy

the greatest therapeutic benefit for patients (near 1.0)

The observed reduction in blood glucose in our patient would reduce lactic acid fermentation in the tumor cells, while the elevation of ketone bodies would fuel normal cells thus protecting them from hypoglycemia and oxidative stress

several independent lines of evidence suggest that cytotoxic effector cells such as T cells and natural killer (NK) cells participate in protecting patients with AML against relapse

A plethora of mechanisms have been proposed to account for the dysfunctional antileukemic lymphocytes in AML, including the production of T-cell- and NK-cell-inhibitory factors by AML blasts,48 a deficient expression of NK-cell receptors on leukemic cells,49 inhibition of antileukemic lymphocytes by mononuclear phagocytes,4 and an impaired stimulatory interaction between the CD28 antigen expressed by T cells and contact antigens on AML blasts

This trial met the primary endpoint and thus showed a significantly improved LFS for patients receiving HDC/IL-2 as compared with the current standard of care

IL-2 is a central T cell-derived cytokine, which induces NK cell and T cell proliferation, differentiation and activation, and also stim-ulates the production of secondary immunostimulatory cytokines

combination of histamine and IL-2 thus triggers efficient NK cell-mediated killing of several types of leukemic cells, including freshly recovered human AML blasts

histamine improves the effects of IL-2 on T cell activation

To date nearly half of known human tumors show a dysregulation of the WNT signaling pathway

It should be also noted that the WNT pathway is not exclusively employed during development or overactivated in cancer. In adults many healthy tissues rely on it for renewal and homeostasis maintenance, most notably the intestine, haematopoietic system, hair, bones and skin. Therefore one might expect adverse reactions in all these organ systems, which has indeed been observed for many WNT-targeting compounds upon attempts to push them into the clinics

The intestine seems to be the most vulnerable in this regard

facilitates the dissemination of cancer cells to distant organs. In addition to facilitating metastasis, EMT is thought to generate cancer stem cells (CSCs), which are generally resistant to apoptosis and to standard chemotherapeutic drugs and radiotherapy

IL‐6, which enhances TGF‐β‐induced EMT changes in NSCLC

aside from TGF‐β and Snail, several other signalling pathways including Notch, Wnt, and integrin are known to activate EMT through transcriptional repression of E‐cadherin

Numerous in vivo and in vitro studies confirm that HBOT induces neurogenesis

HIF-1α is the principal mediator of cellular hypoxia adaptations

activated by hypoxia, HIF-1α causes the transcription of its regulated downstream genes, including erythropoietin (EPO) and VEGF which are known to promote neurogenesis

peak plasma concentrations obtained intravenously are estimated to reach 14 000 μmol/L, and concentrations above 2000 μmol/L may persist for several hours

Emerging in vitro data show that extracellular ascorbic acid selectively kills some cancer but no normal cells by generating hydrogen peroxide

Death is mediated exclusively by extracellular ascorbate, at pharmacologic concentrations that can be achieved only by intravenous administration

Oxidative slow-twitch type I fibres (henceforth briefly called ‘slow fibres’) contain MHC-Iβ. They use oxidative phosphorylation (OXPHOS) to generate ATP and are thus highly fatigue resistant and preferentially activated during endurance exercise. Slow fibres comprise high amounts of mitochondria, myoglobin and lipid droplets, and are well supplied by capillaries

there are three types of fast-twitch fibres (types IIA, IID/X, IIB, with the corresponding MHC isoforms IIa, IId/x, IIb) which are all used for rapid high-force generation. Oxidative-glycolytic fast-twitch type IIA fibres have intermediate amounts of mitochondria, lipid droplets and capillaries, and are intermediately resistant to fatigue (as compared to type I and types IIB and IID/X). Glycolytic fast-twitch type IID/X fibres are poor in mitochondria, lipids and capillaries and more susceptible to fatique than type IIA. Glycolytic fast-twitch type IIB fibres have the lowest amounts of mitochondria, lipid droplets and capillaries, but generate the highest contraction velocities

Several studies have shown that PGC-1α is upregulated after endurance training

Statin use is associated with an increased prevalence and extent of coronary plaques possessing calcium

As compared with individuals not taking statins, those taking statins possessed a significantly higher prevalence of obstructive CAD, as well as higher numbers of vessels with obstructive CAD

non-calcified plaques (NCP)