defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
1More
1More
Measurement of steroid hormones in s... [Scand J Clin Lab Invest. 2013] - PubMed - NCBI - 0 views
1More
Acute phase protein and cytokine levels in... [Brain Behav Immun. 2013] - PubMed - NCBI - 0 views
1More
shared by Nathan Goodyear on 21 Oct 14
- No Cached
Internet Scientific Publications - 0 views
ispub.com/8186
malondialdehyde glutathione GSH superoxide disumutase SOD saliva uric acid MDA stroke disease testing
![](/images/link.gif)
1More
shared by Nathan Goodyear on 21 Oct 14
- No Cached
http://www.iasj.net/iasj?func=fulltext&aId=1538 - 0 views
www.iasj.net/iasj
oxidative stress glutathione GSH malondialdehyde testing superoxide disumutase SOD saliva uric acid
![](/images/link.gif)
1More
Validation of a high-sensitivity assay for... [Brain Behav Immun. 2011] - PubMed - NCBI - 0 views
63More
shared by Nathan Goodyear on 30 Mar 15
- No Cached
Testosterone level in men with type 2 diabetes mellitus and related metabolic... - 0 views
www.ncbi.nlm.nih.gov/...PMC4364844
low T low Testosterone Diabetes Testosterone men male hormones metabolic syndrome
![](/images/link.gif)
-
the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
-
most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
- ...57 more annotations...
-
Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
-
−0.124 nmol/L/year in serum total testosterone
-
In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
-
In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
-
testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
-
testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
-
In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
-
independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
-
Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
-
In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
-
leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
-
Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
-
-
Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
-
As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
-
alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
-
A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
-
Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
-
subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
-
In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
-
Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
-
HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
-
pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
-
In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
-
Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
-
Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
-
The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
-
In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
-
a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
-
the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
-
assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
-
In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
-
a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
-
A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
-
most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
-
MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
-
Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
-
In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
-
weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
-
To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
-
In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
-
low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
-
Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
-
low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
-
European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
-
Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
-
serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
-
Nice review of Testosterone levels and some of the evidence linking Diabetes with low T. However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling. The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
5More
CLINICAL CHARACTERISTICS AND ENDOSCOPIC FINDINGS ASSOCIATED WITH BLASTOCYSTIS HOMINIS I... - 1 views
-
patients with alcoholic cirrhosis and chronic hepatitis experienced more severe symptoms when infected with B. hominis
-
Among the 34 individuals with chronic HBV infection in this study, individuals who harbored B. hominis were more likely to have an abnormal liver function test result than those who did no
- ...1 more annotation...
-
intense inflammatory cell infiltration, edematous lamina propria, and mucosal sloughing. However, the pathogenicity of B. hominis in human intestine has only been elucidated from case reports and a case series study
1More
shared by Nathan Goodyear on 03 Aug 14
- No Cached
Exercise and circulating cortisol levels... [J Endocrinol Invest. 2008] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...18787373
Cortisol exercise hormone hormones ACTH high intensity training low intensity testing
![](/images/link.gif)
1More
shared by Nathan Goodyear on 08 Nov 15
- No Cached
Natriuretic Peptide Testing in Heart Failure - 0 views
circ.ahajournals.org/...2015.full
CHF heart health BNP NT-proBNP cardiovascular disease cardiovascular events
![](/images/link.gif)
1More
shared by wheelchairindia9 on 17 Feb 16
- No Cached
Karman S-Ergo 115 - 0 views
www.wheelchairindia.com/...Karma-S-Ergo-115-Wheelchair
Ergo 115 Wheelchair Ensures Comfortable Ride Ergonomic Manual Wheelchair Ergonomic wheelchairs Karma S Ergo 115 Wheelchair Karma S Ergo 125 Wheelchair Karman S-Ergo 115 Ergonomic Transport Chair
![](/images/link.gif)
-
Ergonomic wheelchairs have been tested and proven to be effective for relieving pressure throughout the body; this is confirmed by pressure chart mapping. Feeling comfortable on a wheelchair is something every user demands out of their new wheelchair, the ergonomic cushion that is included with the ergonomic series provides a level of comfort that is unparalleled. Ergonomic Transport Wheelchair provides the perfect shape to fit the human body to relieve pressure, increase stabilization, weight distribution and lower the risk of pressure sores and scoliosis. Lightweight Ergonomic Wheelchair features wide arm pads for extra support, folding back rest, detachable swing-away footrests, and a Tube-in Center foot-plate that provides extra support for the leg muscles. This wheelchair can hold up to daily use and is excellent for traveling. Ergonomic features flip-back armrest and swing away footrests. A lightweight frame that is 25 lbs. without footrests and a folding backrest allows easy travel or storage. The chair comes equipped with a padded anti-bacterial upholstery that is comfortable and washable. Karma Ergo Lite 2501 Wheelchair: The extremely lightweight Ergo Lite 2501 Transport Wheelchair weighs only 8.16 kg. and features an ergonomically-designed seat and backrest, making it one of the most comfortable transport chairs on the market. The folding seat and backrest make the S-Ergo ideal for storage or travel, and the built in AEGIS anti-bacterial cushion provides added comfort and support. Despite its light weight, the S-Ergo features a 115 kg. weight capacity along with large, 14" flat-free polyurethane rear tires. Karma Ergo Lite 2501 Wheelchair Features: Lightest transporter on the market! Patented S-Style Ergonomic Seat Frame 6061 T-6 Aircraft-grade Aluminum Only 18 lb . (w/ footrests) Built in Silver Aegis Anti-bacterial Cushion Fixed Armrests w/Concaved Armpads Pocket Behind Backrest & Small Carry Pouch on Each Armrest 6" x 1" Polyurethane
37More
Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic... - 0 views
-
Recent reports indicate that a certain ROS concentration is required for high-dose vitamin C to induce cytotoxicity in cancer cells.
-
In this study, we report that PAA is efficacious in killing MM cells in vitro and in vivo models, which generated levels of 20–40 mM ascorbate and 500 nM ascorbyl radicals after intraperitoneal administration of 4 g ascorbate per kilogram of body weight (Chen et al., 2008Chen et al., 2008), in xenograft MM mice
- ...33 more annotations...
-
These data suggest that PAA may show a therapeutic advantage to blood cancers vs solid tumors because of the communication between tumor cells and blood plasma
-
These results strongly suggest that the mechanism of PAA killing of MM cells is indeed iron-dependent
-
These results suggest that PAA administration in SMM may be able to prevent progression to symtomatic MM
-
A recent study by Yun and colleagues demonstrated that vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH, but spares normal cells
-
RAS family genes show the most frequent mutations in MM. KRAS, NRAS and BRAF are mutated in 22%, 20% and 7% of MM samples
-
the disease stage rather than the mutation of RAS and/or BRAF is the major predictive factor for PAA sensitivity in MM treatment
-
Other molecular mechanisms including ATP depletion and ATM-AMPK signaling have been reported to explain PAA-induced cell death
-
Our findings complement reported studies and further address the mechanism of action using clinical samples in which we observed that PAA killed tumor cells with high iron content, suggesting that iron might be the initiator of PAA cytotoxicity
-
combination of PAA with standard therapeutic drugs, such as melphalan, may significantly reduce the dose of melphalan needed
-
Combined treatment of reduced dose melphalan with PAA achieved a significantly longer progression-free survival than the same dose of melphalan alone.
-
These data also suggest that the bone marrow suppression induced by high-dose melphalan can be ameliorated by the combination of PAA with lower dose of melphalan because of the lack of toxicity of PAA on normal cells with low iron content.
-
In MM preclinical and clinical studies, ascorbate was used as an adjunct drug and showed controversial results (Harvey et al., 2009, Perrone et al., 2009, Held et al., 2013, Sharma et al., 2012, Nakano et al., 2011, Takahashi, 2010, Sharma et al., 2009, Qazilbash et al., 2008). However, none of these tests used pharmacological doses of ascorbate and intravenous administration
-
Cameron and Pauling reported that high doses of vitamin C increased survival of patients with cancer
-
pharmacologically dosed ascorbic acid (PAA) 50–100 g (Chen et al., 2008, Padayatty et al., 2004, Hoffer et al., 2008, Padayatty et al., 2006, Welsh et al., 2013), administered intravenously, has potent anti-cancer activity and its role as anti-cancer therapy is being studied at the University of Iowa and in other centers
-
In the presence of catalytic metal ions like iron, PAA administered intravenously exerts pro-oxidant effects leading to the formation of highly reactive oxygen species (ROS), resulting in cell death
-
The survival of CD138+ cells in vitro was significantly decreased following PAA treatment in all 9 MM
-
In contrast, no significant change of cell viability was observed in CD138− BM cells from the same patients
-
the combination of melphalan plus PAA showed greater tumor burden reduction than each drug alone, suggesting a synergistic activity between these two drugs
-
adding deferoxamine (DFO), an iron chelator, to OCI-MY5 cells before PAA treatment was also sufficient to prevent PAA-induced cellular death
-
PAA by reacting with LIP and generating ROS induces mitochondria-mediated apoptosis in which AIF1 cleavage is important for cell death.
1More
Combined effects in toxicology--a rapid systematic testing procedure: cadmium, mercury,... - 0 views
13More
PET/CT Standardized Uptake Values (SUVs) in Clinical Practice and Assessing Response to... - 0 views
-
In some cases, such as Hodgkins lymphoma, quantitative PET/CT imaging may not actually be needed, as success can be defined by the complete absence of tracer uptake in the PET image following a course of standardized therapy
- ...9 more annotations...
-
The utilization of PET/CT to assess response to therapy is increasing in the US related, in part, to the creation and subsequent favorable results of the National Oncologic PET Registry (NOPR)
-
Changes in size as a result of therapy may take many months to develop and any opportunity to make early decisions about therapy success or failure is often unduly delayed or lost altogether
-
measures of changes in metabolic activity via FDG PET/CT can provide an alternate approach to assess response to therapy -- often very early in the course of treatment
-
The true tracer uptake in a patient is composed of two components: the first being the amount of tracer uptake (e.g. FDG) associated with the disease status (the signal of interest), which can be modified by the biophysiological status of the patient. One of the more important patient parameters is the blood glucose level, which has been shown to inversely-linearly affect SUVs
-
A prospective study by Crippa et al.30 in eight patients showed that as blood glucose levels were increased from 92.4 ±10.2 to 158 ± 13.8 mg/100 ml by glucose loading, the average SUV of 20 liver metastases decreased from 9.4 ± 5.7 to 4.3 ± 8.3
-
chemotherapy can result in impaired renal function, significantly reducing the clearance of plasma FDG through the kidney and thus increasing tumor SUV relative to an initial PET scan
-
The biological variability has been estimated in several test-retest studies7,32–35 at approximately 10% for scans repeated within a few days
1More
Prior ingestion of exogenous ketone monoester attenuates the glycemic respons... - 0 views
57More
shared by Nathan Goodyear on 09 Feb 11
- Cached
Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a p... - 0 views
www.pnas.org/...13604.full
IV vitamin C cancer ascorbic acid vitamin C H2O2 GPX glutathione Perioxidase
![](/images/link.gif)
-
Taken together, these data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H2O2, and that blood can be a delivery system of the pro-drug to tissues.
-
These findings give plausibility to i.v. ascorbic acid in cancer treatment, and have unexpected implications for treatment of infections where H2O2 may be beneficial
-
pharmacologic concentrations of ascorbate killed cancer but not normal cells, that cell death was dependent only on extracellular but not intracellular ascorbate, and that killing was dependent on extracellular hydrogen peroxide (H2O2) formation with ascorbate radical as an intermediate
- ...48 more annotations...
-
Our data show that ascorbic acid selectively killed cancer but not normal cells, using concentrations that could only be achieved by i.v. administration
-
Ascorbate-mediated cell death was due to protein-dependent extracellular H2O2 generation, via ascorbate radical formation from ascorbate as the electron donor. Like glucose, when ascorbate is infused i.v., the resulting pharmacologic concentrations should distribute rapidly in the extracellular water space (42). We showed that such pharmacologic ascorbate concentrations in media, as a surrogate for extracellular fluid, generated ascorbate radical and H2O2. In contrast, the same pharmacologic ascorbate concentrations in whole blood generated little detectable ascorbate radical and no detectable H2O2. These findings can be accounted for by efficient and redundant H2O2 catabolic pathways in whole blood (e.g., catalase and glutathione peroxidase) relative to those in media or extracellular fluid
-
ascorbic acid administered i.v. in pharmacologic concentrations may serve as a pro-drug for H2O2 delivery to the extracellular milieu
-
H2O2 generated in blood is normally removed by catalase and glutathione peroxidase within red blood cells, with internal glutathione providing reducing equivalents
-
The electron source for glutathione is NADPH from the pentose shunt, via glucose-6-phosphate dehydrogenase. If activity of this enzyme is diminished, the predicted outcome is impaired H2O2 removal causing intravascular hemolysis, the observed clinical finding.
-
Only recently has it been understood that the discordant clinical findings can be explained by previously unrecognized fundamental pharmacokinetics properties of ascorbate
-
Intracellular transport of ascorbate is tightly controlled in relation to extracellular concentration
-
Intravenous ascorbate infusion is expected to drastically change extracellular but not intracellular concentrations
-
For i.v. ascorbate to be clinically useful in killing cancer cells, pharmacologic but not physiologic extracellular concentrations should be effective, independent of intracellular ascorbate concentrations.
-
There was no correlation with ascorbate-induced cell death and glutathione, catalase activity, or glutathione peroxidase activity.
-
H2O2, as the product of pharmacologic ascorbate concentrations, has potential therapeutic uses in addition to cancer treatment, especially in infections
-
Use of ascorbate as an H2O2-delivery system against sensitive pathogens, viral or bacterial, has substantial clinical implications that deserve rapid exploration.
-
Recent pharmacokinetics studies in men and women show that 10 g of ascorbate given i.v. is expected to produce plasma concentrations of nearly 6 mM, which are >25-fold higher than those concentrations from the same oral dose
-
As much as a 70-fold difference in plasma concentrations is expected between oral and i.v. administration,
-
Complementary and alternative medicine practitioners worldwide currently use ascorbate i.v. in some patients, in part because there is no apparent harm
-
We first investigated whether ascorbate in pharmacologic concentrations selectively affected the survival of cancer cells by studying nine cancer cell lines
-
Clinical pharmacokinetics analyses show that pharmacologic concentrations of plasma ascorbate, from 0.3 to 15 mM, are achievable only from i.v. administration
-
plasma ascorbate concentrations from maximum possible oral doses cannot exceed 0.22 mM because of limited intestinal absorption
-
For five of the nine cancer cell lines, ascorbate concentrations causing a 50% decrease in cell survival (EC50 values) were less than 5 mM, a concentration easily achievable from i.v. infusion
-
All tested normal cells were insensitive to 20 mM ascorbate.
-
As ascorbate concentration increased, the pattern of death changed from apoptosis to pyknosis/necrosis, a pattern suggestive of H2O2-mediated cell death
-
Apoptosis occurred by 6 h after exposure, and cell death by pyknosis was ≈90% at 14 h after exposure
-
In contrast to lymphoma cells, there was little or no killing of normal lymphocytes and monocytes by ascorbate
-
Ascorbate is transported into cells as such by sodium-dependent transporters, whereas dehydroascorbic acid is transported into cells by glucose transporters and then immediately reduced internally to ascorbate
-
Whether or not intracellular ascorbate was preloaded, extracellular ascorbate induced the same amount and type of death.
-
extracellular ascorbate in pharmacologic concentrations mediates death of lymphoma cells by apoptosis and pyknosis/necrosis, independently of intracellular ascorbate.
-
Because these data implicated H2O2 in cell killing, we added H2O2 to lymphoma cells and studied death patterns using nuclear staining (19, 28). The death patterns found with exogenous H2O2 exposure were similar to those found with ascorbate
-
For both ascorbate and H2O2, death changed from apoptosis to pyknosis/necrosis as concentrations increased
-
Sensitivity to direct exposure to H2O2 was greater in lymphoma cells compared with normal lymphocytes and normal monocytes
-
There was no association between the EC50 for ascorbate-mediated cell death and intracellular glutathione concentrations, catalase activity, or glutathione peroxidase activity
-
H2O2 generation was dependent on time, ascorbate concentration, and the presence of trace amounts of serum in media
-
whatever H2O2 is generated should be removed by glutathione peroxidase and catalase within red blood cells, because H2O2 is membrane permeable
-
The data are consistent with the hypothesis that ascorbate in pharmacologic concentrations is a pro-drug for H2O2 generation in the extracellular milieu but not in blood.
-
In patients with glucose-6-phosphate dehydrogenase deficiency, i.v. ascorbate is contraindicated because it causes intravascular hemolysis
-
ascorbate, an electron-donor in such reactions, ironically initiates pro-oxidant chemistry and H2O2 formation
-
data here showed that ascorbate initiated H2O2 formation extracellularly, but H2O2 targets could be either intracellular or extracellular, because H2O2 is membrane permeant
-
More than 100 patients have been described, presumably without glucose-6-phosphate dehydrogenase deficiency, who received 10 g or more of i.v. ascorbate with no reported adverse effects other than tumor lysis
12More
From the Cover: Pharmacologic doses of ascorbate act as a prooxidant and decrease growt... - 0 views
-
An extensive panel of 43 tumor and 5 normal cell lines were exposed to ascorbate in vitro for ≤2 h to mimic clinical pharmacokinetics
-
effective concentration that decreased survival 50% (EC50) was determined. EC50 was <10 mM for 75% of tumor cells tested, whereas cytotoxicity was not evident in normal cells with >20 mM ascorbate
-
The addition of catalase to the medium ameliorated death of ovarian carcinoma (Ovcar5), pancreatic carcinoma (Pan02), and glioblastoma (9L) cells exposed to 10 mM ascorbate (1 h), indicating cytotoxicity was mediated by H2O2
- ...8 more annotations...
-
A treatment dose of 4 g ascorbate/kg body weight either once or twice daily did not produce any discernible adverse effects
-
Xenograft experiments showed that parenteral ascorbate as the only treatment significantly decreased both tumor growth and weight by 41–53%
-
Pharmacologic concentrations of ascorbate decreased tumor volumes 41–53% in diverse cancer types known for both their aggressive growth and limited treatment options.
-
Our findings showed that pharmacologic ascorbic acid concentrations were cytotoxic to many types of cancer cells in vitro (Fig. 1A) and significantly impeded tumor progression in vivo without toxicity to normal tissues
-
The amelioration of ascorbate cytotoxicity in vitro by the addition of catalase was consistent among sensitive cancer cells (Fig. 1B) and points unambiguously to H2O2 generation in the extracellular medium
-
the current in vivo data support that pharmacologic ascorbate concentrations, which can readily be achieved in humans (Fig. 3E), diminished growth of several aggressive cancer types in mice (Fig. 2) without causing apparent adverse effects.
-
These intratumoral H2O2 concentrations of >125 μM persisted for >3 h after ascorbate administration
35More
Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside - 0 views
-
MAF precursor activity has also been lost or reduced after Gc-globulin treatment in some cancer cell lines
-
This appears to result from the deglycosylated ɑ-N-acetylgalactosaminidase (nagalase) secreted from cancerous cells
- ...31 more annotations...
-
Studies have shown that the production of nagalase has a mutual relationship with Gc-MAF level and immunosuppression
-
It has been demonstrated that serum levels of nagalase are good prognosticators of some types of cancer
-
The nagalase level in serum correlates with tumor burden and it has been shown that Gc-MAF therapy progresses, nagalase activity decreases
-
It has been shown that Gc-MAF can inhibit the angiogenesis induced by pro-inflammatory prostaglandin E1
-
The effect of Gc-MAF on chemotaxis or activation of tumoricidal macrophages is likely the main mechanism against angiogenesis.
-
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.”
-
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
-
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.”
-
Yamamoto et al. showed that the administration of Gc-MAF to 16 patients with prostate cancer led to improvements in all patients without recurrence
-
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
-
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).
-
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
-
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
-
weekly administration of 100 ng Gc-MAF to cancer at different stages and types showed curative effects at different follow-up times
-
Studies have shown that weekly administration of 100 ng Gc-MAF to cancer patients had curative effects on a variety of cancers
-
Because the half-life of the activated macrophages is approximately one week, it must be administered weekly
-
In vivo weekly intramuscular administration of Gc-MAF (100 ng) for 16-22 weeks was used to treat patients with breast cancer
-
individuals harboring different VDR genotypes had different responses to Gc-MAF and that some genotypes were more responsive than others
-
Administration of Gc-MAF for cancer patients exclusively activates macrophages as an important cell in adaptive immunity
-
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
-
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
-
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
-
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
-
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).
-
Activating or modifying natural killer cells, dendritic cells, DC, CTL, INF and IL-2 have all been recommended for cancer immunotherapy
-
It has been reported that nagalase cannot deglycosylate Gc-MAF as it has specificity for Gc globulin alone
-
inflammation-derived macrophage activation with the participation of B and T lymphocytes is the main mechanism
-
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
50More
shared by Nathan Goodyear on 30 Jan 18
- No Cached
Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2... - 0 views
www.nature.com/...s41698-017-0044-8
cancer cancer stem cells liver cancer vitamin C IV vitamin C oncology
![](/images/link.gif)
-
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)
- ...41 more annotations...
-
differential sensitivity to VC may result from variations in VC flow into cells, which is dependent on SVCT-2 expression.
-
high-dose VC significantly impaired both the tumorspheres initiation (Fig. 4d, e) and the growth of established tumorspheres derived from HCC cells (Fig. 4f, g) in a time-dependent and dose-dependent manner.
-
The antioxidant, N-acetyl-L-cysteine (NAC), preventing VC-induced ROS production (a ROS scavenger), completely restored the viability and colony formation among VC-treated cells
-
Interestingly, the combination of VC and cisplatin was even more effective in reducing tumor growth and weight
-
Consistent with the in vitro results, stemness-related genes expressions in tumor xenograft were remarkably reduced after VC or VC+cisplatin treatment, whereas conventional cisplatin therapy alone led to the increase of CSCs
-
Interestingly, at extracellular concentrations greater than 1 mM, VC induces strong cytotoxicity to cancer cells including liver cancer cells
-
we hypothesized that intravenous VC might reduce the risk of recurrence in HCC patients after curative liver resection.
-
Intriguingly, the 5-year disease-free survival (DFS) for patients who received intravenous VC was 24%, as opposed to 15% for no intravenous VC-treated patients
-
In this study, based on the elevated expression of SVCT-2, which is responsible for VC uptake, in liver CSCs, we revealed that clinically achievable concentrations of VC preferentially eradicated liver CSCs in vitro and in vivo
-
Additionally, we found that intravenous VC reduced the risk of post-surgical HCC progression in a retrospective cohort study.
-
Three hundred thirty-nine participants (55.3%) received 2 g intravenous VC for 4 or more days after initial hepatectomy
-
As the key protein responsible for VC uptake in the liver, SVCT-2 played crucial roles in regulating the sensitivity to ascorbate-induced cytotoxicity
-
we also observed that SVCT-2 was highly expressed in human HCC samples and preferentially elevated in liver CSCs
-
we revealed that VC treatment dramatically reduced the self-renewal ability, expression levels of CSC-associated genes, and percentages of CSCs in HCC, indicating that CSCs were more susceptible to VC-induced cell death
-
as a drug for eradicating CSCs, VC may represent a promising strategy for treatment of HCC, alone or particularly in combination with chemotherapeutic drugs
-
In HCC, we found that VC-generated ROS caused genotoxic stress (DNA damage) and metabolic stress (ATP depletion), which further activated the cyclin-dependent kinase inhibitor p21, leading to G2/M phase cell cycle arrest and caspase-dependent apoptosis in HCC cells
-
we demonstrated a synergistic effect of VC and chemotherapeutic drug cisplatin on killing HCC both in vitro and in vivo
-
Intravenous VC has also been reported to reduce chemotherapy-associated toxicity of carboplatin and paclitaxel in patients,38 but the specific mechanism needs further investigation
-
Our retrospective cohort study also showed that intravenous VC use (2 g) was related to the improved DFS in HCC patients after initial hepatectomy
-
several clinical trials of high-dose intravenous VC have been conducted in patients with advanced cancer and have revealed improved quality of life and prolonged OS
-
high expression (grade 2+/3+) of SVCT-2 was in agreement with poorer overall survival (OS) of HCC patients (Fig. 1c) and more aggressive tumor behavior
-
these data suggest that SVCT-2 is preferentially expressed in liver CSCs and is required for the maintenance of liver CSCs.
-
pharmacologic concentrations of plasma VC higher than 0.3 mM are achievable only from i.v. administration
-
The viabilities of HCC cells were dramatically decreased after exposure to VC in dose-dependent manner
-
These results verify that VC inhibits tumor growth in HCC PDX models and SVCT-2 expression level is associated with VC response
-
qPCR and IHC analysis demonstrated that expression levels of CSC-associated genes and percentages of CSCs in PDXs dramatically declined after VC treatment, confirming the inhibitory role of VC in liver CSCs
2More
Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras | Nature Communi... - 0 views
-
glucose deprivation triggers apoptosis47 and vitamin C treatment kills RAS-oncogene expressing tumor cells, but not wild-type RAS containing cells, by inhibition of GAPDH