Dr. Krebs' Jr paper on nitrilosides i.e. laetril or vitamin B17 in its use in the fight against cancer. This is a reprint from the Journal of Applied Nutrition from 1970.
beta glucan (β-glucan), which is a dietary fiber readily found in oat and barley bran
Among cereals, the highest content (g per 100 g dry weight) of β-glucan has been reported for barley: 2–20 g (65% is water-soluble fraction) and for oats: 3–8 g (82% is water-soluble fraction). Other cereals also contain β-glucan but in much lower amounts: sorghum 1.1–6.2 g, rye 1.3–2.7 g, maize 0.8–1.7 g, triticale 0.3–1.2 g, wheat 0.5–1.0 g, durum wheat 0.5-0.6 g, and rice 0.13 g
Other sources of β-glucan include some types of seaweed [17] and various species of mushrooms such as Reishi, Shiitake, and Maitake [18].
Distinction between soluble and insoluble dietary fibers is based on the solubility characteristics of dietary fiber in hot aqueous buffer solutions
Insoluble fibers primarily consist of cellulose and some hemicelluloses, resistant starch, and chitin while soluble fibers include pectins, β-glucans, galactomannan gums, mucilages, and some hemicelluloses
insoluble fibers increase fecal bulk and the excretion of bile acids and decrease intestinal transit time
Soluble fibers increase total transit time by delaying gastric emptying and also slow glucose absorption
only soluble viscous fibers delay gastric emptying time and slow glucose absorption while nonviscous soluble fibers primarily act as a substrate for microbial fermentation in the colon
Azad et al [15] used single photon emission computed tomography and showed that, after 3~5 weeks of TRT, cerebral perfusion was increased in the midbrain and the superior frontal gyrus in seven men with hypogonadism
After 12~14 weeks, increased perfusion was still observed in the midbrain as well as in the midcingulate gyrus
TDS patients who received TRT showed significant improvement in cognitive function only if mild cognitive impairment was present at baseline
Cherrier et al [17] evaluated a sample of 32 subjects, which included 17 men with mild cognitive impairment and 15 with Alzheimer's disease. At the 6-week follow-up, patients who received TRT showed significantly better scores regarding spatial memory, constructional abilities, and verbal memory compared to those noted in the placebo group. Taken together, these results suggest that TRT has a beneficial effect on cognitive function
TRT improved mood and well-being, and reduced fatigue and irritability in hypogonadal men
The study by Pope et al [20] involved men with depression refractory to standard anti-depressants, and found that TRT lowered the Hamilton Depression score,
depression tends to increase as testosterone levels decrease [21], it is highly likely that TRT improved symptoms of depression by increasing testosterone levels.
Under hypoxic conditions, tumour cells primarily use glycolysis for energy, producing
lactate, which is expelled to the tumour microenvironment, allowing tumours to continue
their glycolytic activity
Sonveaux et al. showed that lactate, which is generally considered a waste product, is preferred
over glucose by oxidative tumour cells as their primary energy source
MCT4 is a low-affinity transporter, which is abundant in highly glycolytic muscle
cells and is one of the many target genes of hypoxia-inducible factor 1 alpha (HIF-1α)
Other targets of HIF-1α include glucose transporter-1 (GLUT-1), the main transporter
involved in glucose uptake [9,10]; lactate dehydrogenase V (LDHV), which is responsible for the conversion of pyruvate
into lactate; pyruvate dehydrogenase kinase isozyme 1 (PDK1), which is responsible
for the phosphorylation and consequent inactivation of pyruvate dehydrogenase (PDH);
and carbonic anhydrase IX (CAIX), a hypoxia-related protein involved in pH regulation
[11]. Alpha-methylacyl-CoA racemase (AMACR), pristanoyl-CoA oxidase (ACOX-3) and D-bifunctional
protein (DBP), are also important fatty acid oxidation-related proteins in prostate
cancer
the essential role played by the cross-talk between stroma and epithelium
in carcinogenesis and prostate cancer progression has been increasingly recognised
strong membranous expression of MCT1 was consistently observed in cancer
cells, suggesting a role for MCT1 in the transport of lactate into tumour cells from
the acidic extracellular matrix, suggesting that lactate might be used as a fuel by
oxidative cancer cells.
Our hypothesis is in agreement with those of Fiaschi et al.[17], who describe the metabolic reprogramming of CAFs towards the Warburg phenotype as
a result of contact with prostate cancer cells
Using in vitro studies, they showed lactate production and efflux by de novo expressed MCT4 in CAFs and also demonstrated that, upon contact with CAFs, prostate
cancer cells were reprogrammed towards aerobic metabolism, with an increase in lactate
uptake via the lactate transporter MCT1.
pharmacological inhibition of
MCT1-mediated lactate uptake dramatically affected PCa cell survival and tumour outgrowth
In this model, “energy transfer” or “metabolic coupling” between the
tumour stroma and epithelial cancer cells fuels tumour growth and metastasis via oxidative
mitochondrial metabolism in anabolic cancer cells
the concomitant expression of MCT1 in tumour cells and MCT4
in fibroblasts in the same tissue is clinically significant, and associated with poor
prognosis.
pharmacological concentrations of AA can sensitize cancer cells to chemotherapy, enhancing its antineoplastic effect
synergistic effect with conventional chemotherapeutic drugs is a fact already reported, in various types of cancer, by numerous authors, namely in pancreatic (Espey et al., 2011), prostate (Gilloteaux et al., 2014), lung (Lee et al., 2017), breast (Kurbacher et al., 1996; Wu et al., 2017) and ovarian (Ma et al., 2014) cancers.
chemosensitizing effect of vitamin C has already been proven by several authors in various types of cancer
intravenous pharmacological concentrations, may not only potentiate the effects of conventional chemotherapy, but also improve the quality of life of cancer patients
AA reinforced the anti-proliferative activity of 5-FU
Combined treatment induced a reduction of 11.5% and 43% in cell viability compared with AA or Iri therapies, respectively, emphasizing the synergistic effect
cytotoxic effect occurred with treatment with Iri alone, but also this effect was further potentiated by the presence of AA.
association of AA with Oxa showed very promising results, considering that a synergistic effect was demonstrated, in almost all conditions
AA and Oxa seem to act synergistically by the activation of the intrinsic pathway of apoptosis, translated on the statistically significant increase of the ratio between BAX and BCL-2 proteins, which in turn is associated with a decrease of Δψm