Group items tagged

“Intrinsic processes” include those that result in mutations due to random errors in DNA replication whereas “extrinsic factors” are environmental factors that affect mutagenesis rates (such as UV radiation, ionizing radiation, and carcinogens

intrinsic factors do not play a major causal role.

intrinsic cancer risk should be determined by the cancer incidence for those cancers with the least risk in the entire group controlling for total stem cell divisions

if one or more cancers would feature a much higher cancer incidence, for example, lung cancer among smokers vs. non-smokers, then this most likely reflects additional (and probably extrinsic) risk factors (smoking in this case)

Particularly, for breast and prostate cancers, it has long been observed that large international geographical variations exist in their incidences (5-fold for breast cancer, 25-fold for prostate cancer)14, and immigrants moving from countries with lower cancer incidence to countries with higher cancer rates soon acquire the higher risk of their new country

Colorectal cancer is another high-incidence cancer that is widely considered to be an environmental disease17, with an estimated 75% or more colorectal cancer risk attributable to diet

melanoma, its risk ascribed to sun exposure is around 65–86%

non-melanoma basal and squamous skin cancers, ~90% is attributable to UV

75% of esophageal cancer, or head and neck cancer are caused by tobacco and alcohol

HPV may cause ~90% cases in cervical cancer23, ~90% cases in anal cancer24, and ~70% in oropharyngeal cancer

HBV and HCV may account for ~80% cases of hepatocellular carcinoma

H pylori may be responsible for 65–80% of gastric cancer

While a few cancers have relatively large proportions of intrinsic mutations (>50%), the majority of cancers have large proportions of extrinsic mutations, for example, ~100% for Myeloma, Lung and Thyroid cancers and ~80–90% for Bladder, Colorectal and Uterine cancers, indicating substantial contributions of carcinogen exposures in the development of most cancers

onsistent estimate of contribution of extrinsic factors of >70–90% in most common cancer types. This concordance lends significant credibility to the overall conclusion on the role of extrinsic factors in cancer development

malnutrition progressing to cachexia is another common manifestation of cirrhosis

Malnutrition can be mitigated with BCAA supplementation

Studies show that administration of amino acid formulas enriched with BCAAs can reduce protein loss, support protein synthesis, and improve nutritional status of patients with chronic liver disease

Leucine has been shown to be the most effective of the BCAAs because it acts via multiple pathways to stimulate protein synthesis

BCAAs metabolites inhibit proteolysis

Patients with cirrhosis have both insulin deficiency and insulin resistance

BCAAs (particularly leucine) help to reverse the catabolic, hyperglucagonemic state of cirrhosis both by stimulating insulin release from the pancreatic β cells and by decreasing insulin resistance allowing for better glucose utilization

Coadministration of BCAAs and glucose has been found to be particularly useful

BCAA supplementation improves protein-energy malnutrition by improving utilization of glucose, thereby diminishing the drive for proteolysis, inhibiting protein breakdown, and stimulating protein synthesis

Cirrhotic patients have impaired immune defense, characterized by defective phagocytic activity and impaired intracellular killing activity

another effect of BCAA supplementation is improvement of phagocytic function of neutrophils and possibly improvement in natural killer T (NKT) cell lymphocyte activity

BCAA supplementation may reduce the risk of infection in patients with advanced cirrhosis not only through improvement in protein-energy malnutrition but also by directly improving the function of the immune cells themselves

BCAA administration has also been shown to have a positive effect on liver regeneration

A proposed mechanism for improved liver regeneration is the stimulatory effect of BCAAs (particularly leucine) on the secretion of hepatocyte growth factor by hepatic stellate cells

BCAAs activate rapamycin signaling pathways which promotes albumin synthesis in the liver as well as protein and glycogen synthesis in muscle tissue

Chemical improvement with BCAA treatment is demonstrated by recovery of serum albumin and lowering of serum bilirubin levels

long-term oral BCAA supplementation was useful in staving off malnutrition and improving survival by preventing end-stage fatal complications of cirrhosis such as hepatic failure and gastrointestinal bleeding

The incidence of death by any cause, development of liver cancer, rupture of esophageal varices, or progression to hepatic failure was decreased in the group that received BCAA supplementation

Patients receiving BCAA supplementation also have a lower average hospital admission rate, better nutritional status, and better liver function tests

patients taking BCAA supplementation report improved quality of life

BCAAs have been shown to mitigate hepatic encephalopathy, cachexia, and infection rates, complications associated with the progression of hepatic cirrhosis

BCAAs make up 20-25% of the protein content of most foods

Highest levels are found in casein whey protein of dairy products and vegetables, such as corn and mushrooms. Other sources include egg albumin, beans, peanuts and brown rice bran

In addition to BCAAs from diet, oral supplements of BCAAs can be used

Oral supplementation tends to provide a better hepatic supply of BCAAs for patients able to tolerate PO nutrition as compared with IV supplementation, especially when treating symptoms of hepatic encephalopathy

Coadministration of BCAAs with carnitine and zinc has also been shown to increase ammonia metabolism further reducing the encephalopathic symptoms

Cirrhotic patients benefit from eating frequent, small meals that prevent long fasts which place the patient in a catabolic state

the best time for BCAA supplementation is at bedtime to improve the catabolic state during starvation in early morning fasting

A late night nutritional snack reduces symptoms of weakness and fatigability, lowers postprandial hyperglycemia, increases skeletal muscle mass,[25] improves nitrogen balance, and increases serum albumin levels.[26] Nocturnal BCAAs even improve serum albumin in cirrhotic patients who show no improvement with daytime BCAAs

Protein-energy malnutrition (PEM), with low serum albumin and low muscle mass, occurs in 65-90% of cases of advanced cirrhosis

hyperglucagonemia results in a catabolic state eventually producing anorexia and cachexia

BCAAs are further depleted from the circulation due to increased uptake by skeletal muscles that use the BCAAs in the synthesis of glutamine, which is produced in order to clear the ammonia that is not cleared by the failing liver

patients with chronic liver disease, particularly cirrhosis, routinely have decreased BCAAs and increased aromatic amino acids (AAAs) in their circulation

Maintaining a higher serum albumin in patients with cirrhosis is associated with decreased mortality and improved quality of life

the serum BCAA concentration is strongly correlated with the serum albumin level