Metabolism Disorders

The cause of metabolic changes in cancer patients remains unclear. However, several mechanisms that play a role is the presence of a systemic response mediated by hormonal factors distant induced tumors (neuroendocrine axis), the non-specific response to factors released by tumors, the response systemic inflammation mediated by cytokines produced by macrophages. cytokines is a group of various soluble glycoproteins and low molecular weigh peptides that regulate interactions between cells and the function of cells and tissues. In relation with cancer of cachexia, cytokines regulate gastric motility and emptying via the gastrointestinal tract or central nervous system by disrupting efferent signals that regulate satiety. Several hormones and cytokines that play a role in metabolic disorders are: TNF suppress lipoprotein lipase activity in adipocytes, thereby disrupting kliren triglicerida of plasma and cause hypertriglyceridemia; IL-1 causes anorexia through blocking neuropeptide Y (NPY) induced feeding, NPY is a potent feeding stimulatory peptides which are activated by a decrease in leptin levels; TNF and IL-1 increased levels of corticotrophin releasing hormone which is a neurotransmitter in the central nervous and release of glucose-sensitive neurons causes a decrease in the intake food, and IL-6, leukemia inhibitor factor (LIF) produced by cancer cells particularly skeletal muscle causing a potent cachectic effects; IFN-γ also causes of cachexia; lipid-mobilizing factor causing lipolysis and weight loss; proteolysis Inducing factor (PIF) causes the degradation of proteins in skeletal muscle through increased regulation of ubiquitin proteasome proteolytic pathway, reducing the synthesis protein and increase cytokines and acute phase proteins; Leptin controls the intake food and energy expenditure through effector neuropeptic moleculs in hypothalamus, leptin stimulates catabolic pathways and inhibits anabolic pathways, TNF, IL- 1 and LIF increases levels of leptin cause anorexia by preventing normal mechanism of reduction in food intake; uncoupling protein (UPC) 1, 2 and 3 that plays a role in the formation of ATP energy and influential of energy expenditure, its expression is influenced by the product of the tumor (cytokines). For example, in patients with lung cancer small cell obtained an average increase of 37% of basal energy expenditur, so intake of food provided is not sufficient for the body, causing negative energy balance and weight loss.

Hemostasis glucose: glucose is the main energy source for tumor cells and host, increasing use will be accompanied by an increased release of lactate then regenerated into glucose by the liver through coricycle. enhancement coricycle This will increase the energy loss of about 300 kcal per day. Increased gluconeogenesis to maintain glucose hemostasis. Amino acids, glycerol and fat breakdown is used for gluconeogenesis in the liver to to form glucose (plasma levels of alanine, glycine and glutamine decreased). Production of glucose, glucose intolerance and increased insulin resistance. The release of counter regulatory hormones such as glucocorticoid and glucagons increases insulin resistance, so the use of glucose by skeletal muscle decreased.

Protein metabolism: increased muscle catabolism (muscle wasting) caused asthenia or decrease in strength caused by an increase in breakdown protein and a decrease in muscle protein synthesis, increase in liver protein synthesis (acute phase proteins) and tumors. Negative nitrogen balance occurs where there is an increase Whole body protein turnover and turnover aminoacid disorders. Metabolism of fat: the patient will experience a loss of fat tissue due to increased lipolysis and decreased lipogenesis. Turnover of glycerol and free Fathy acid (FFA) increased, decreased levels of lipoprotein lipase causes clearance of plasma triglycerides decreased, increased triglyceride levels, high and low density lipoprotein decreases.

Antitumor Treatment Side Effects

Nutritional deficiencies due to surgery depends on tumor location, extent resection of the gastrointestinal tract and the presence or absence vagotomi action. Operations on the part gastrointestinal tract such as the tongue, mandible, pharynx, esophagus, stomach may decrease ability of swallowing and digestion of food. Extensive small intestine resection causes nutrient absorption disorders, fluids and electrolytes, pancreatic resection can lead to malabsorption of fats and proteins. 

Chemotherapy can cause nausea, vomiting, abdominal pain, mukositis, ileus diarrhea and malabsorption. Some preparations antineopalstik which often causes gastrointestinal symptoms (40%), among others, cisplatin, doxorubicin, fluorouracil. The use of opioid analgesic drugs can cause nausea, constipation and gas distension in the small intestine and large intestine, causing malabsorption (Narcotic bowel syndrome), use of diuretics cause a decrease zinc levels resulting in decreased sense of taste.

Radiotherapy can provide acute and delayed reactions reaction (complications chronic). Acute reactions can occur within 3 days to 1 week of therapy, can be difficulty swallowing due to edema and mukositis oropharynx that causes dysphagia and odinofagia, decreased saliva production with consequent decrease in the enzyme (head neck radiation), nausea vomiting, enteritis or diarrhea (radiation abdominal region). Late complications of persistent mucosal inflammation, intestinal fibrosis and stricture.

Other circumstances that accompany cancer patients such as infection, Diabetes mellitus, rheumatic diseases and others.

 

Autonomic Failure

Clinical manifestations of the syndrome include cardiovascular (postural hypotension, syncope and fixed heart rate) and gastrointestinal symptoms (nausea, anorexia, constipation and sometimes diarrhea). Occurs in approximately 52% of cancer patients particularly advanced stage.

Factors that Increase the Risk of Malnutrition

The cause of malnutrition in cancer patients is multifactorial, generally the causes are grouped into two categories namely : 

• The reduced of food intake and malabsorption.
• Disruption of metabolic processes

Bruera classifying the cause of cachexia in cancer patients as following :

•  Psychological factors and central nervous system (unwillingness to eat, disturbance soy sauce taste perception, psychological stress).
•  Tumor effect (mechanical obstruction, the use of substrate / nutrient by the tumor, the production of cytokines by tumor cells, lipid-mobilizing factors).
•  Effects who associated with therapy (chemotherapy, radiation, surgery, nausea, stomatitis, xerostomia, pain, ileus).
•  Effects who associated with the patient (an increase resting energy expenditure, impaired metabolism, cytokine production by macrophages, autonomic dysfunction, decreased gastric emptying.

  

The reduced of food intake and Malabsorption.

 Tumor effect

The direct effects: 

Tumors of the GI tract such as tumors of the tongue, pharynx, esophagus and stomach that causes obstruction or tumor from outside the gastrointestinal tract that cause obstruction antaralain head neck tumors, pancreas, liver or other tumors that metastasize to the abdominal. Impaired digestion and absorption pankres for example in cancer, lymphoma small intestine, colon tumor vilous. 

Indirect effects (remote effect). 

 The tumor can cause anorexia without directly involving the gastrointestinal tract. It occurs due to a decrease in sense of taste, the quality of smell, disturbance neuroendocrine, disorders of the hypothalamic appetite control center resulting in impaired control of food intake.

Nutritional Theraphy in Cancer Patients

Nutrition is the process when the body uses food for form of energy, maintain health, growth, and to continuing the normal functioning of each organ and tissu. Normal nutritional status describes the fine balance between intake nutrition with nutritional needs. Nutritional deficiencies give undesirable effects on the structure and function of almost all organs and body systems. Malnutrition and Cachexia frequently occurs in cancer patients (24% in stage Early and> 80% at an advanced stage), AIDS and other chronic diseases. Malnutrition and Cachexia increase morbidity and mortality and decreased quality of life, "Survival" of patients. Generally, Patients with malnutrition  can not tolerate therapy including chemotherapy and radiation have more tendency to "adverase effect" on cancer therapy.

Cachexia is a state of malnutrition characterized by anorexia, weight loss, muscle wasting, asthenia, depression, chronic nausea and anemia are usually cause psychological distress, changes in body composition, disruptions in metabolism of carbohydrates, fats and proteins, tissue fluid, acid-base balance, levels of vitamins and electrolytes.

Anorexia is the lack of desire to eat and show that a person does not have an interest (interest) on all food, definition of control of food intake is influenced by a variety of complex organs, environment and peripheral mechanisms (intestinal wall contribute to the regulation of apetite and react to mechanical stimuli such as peptide produced in intestines, among others cholecycstokinin, somatostatin , glucagons) and central (lane hipotalamaus: influenced by perciuman, soy sauce flavor, visual stimuli, temperature, gastrointestinal stimuli through N.vagus, glucose and amino acids in the blood and cortical centers: influenced by the environment, cultural, economic and emotional factors).

Malnutrition is the loss / weight loss above 10% or weight less than 80% ideal weight, within a period of 3 month.When a person is diagnosed with cancer, then nutrition is part of therapy. The main objective nutritional therapy in cancer patients is to maintain or improve the nutritional status so as to minimize the occurrence of complications increase the effectiveness of cancer therapy (surgery, chemotherapy, radiation) quality of life and patient survival . 

THE PREVALENCE OF MALNUTRITION

The prevalence of malnutrition in cancer patients depends on tumor type, stage, organ involved, anticancer therapy, non-malignant conditions that accompany such diabetes mellitus, gastrointestinal diseases and others. In the multicenter study against 12 types of cancer, the prevalence decreased of body weight (BW) by 31% -40% in patients with breast cancer, hematologic cancer and sarcoma; 54% -64% in patients with colon cancer, prostate and lung> 80% in patients with pancreatic cancer and stomach and found the most severe weight loss. Cancer therapy also affects the nutritional status of patients. In a study obtained> 40% of patients who received cancer treatment (surgery, chemotherapy and radiation) are malnourished.

Type, Metastasis, Treatment and Liver Cancer Chemotheraphy Drugs..

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TYPE OF LIVER CANCER.

Primary Liver Cancer 

• Cholangio Carcinoma, cancer that starts in the bile duct.  
• Hepatoblastoma, generally attacking children or child who experienced puberty. 
• Angiosarcoma, a rare cancer, began in the existing blood vessels in the liver. 
• Hepatoma (HCC)-originated in hepatocytes and can spread to other organs. Men are twice as prone to this disease than women.

Secondary Liver Cancer

Secondary liver cancer can arise from primary liver cancer in other organs. But, generally its sourced from the stomach, pancreas, colon, and rectum

M E T A S T A S I S

Normal cells can turn into cancer cells are caused by expression of oncogenes. Oncogene originated from the proto-oncogenes (involved in the activity of normal eukaryotic cell growth) are mutated. If the oncogene is active, then the cells will have uncontrolled growth.

TREATMENTTREATMENT FOR LIVER CANCER

• Surgery.

• Radiation therapy.

• Chemotherapy.

• Kemoembolisasi.

• Gene Therapy.

• Cryotherapy.

• Radiofrequency ablation.

• Transplant.

 Supplementation of vitamin B3 or niacin reported also can prevent cancer. This vitamin is usually also be given in patients with cancer who are undergoing chemotherapy, to reduce the toxic effects (toxicity) of chemotherapy itself.

Alkilgliserol are widely available in fish liver oils shark, co enzyme Q10, butyric acid,, cartilage antiangiogenesis factor (from sharks) that serves prevent the formation of new blood in the spread cancer cells.  Also, omega-3 from fish oil, omega 6 as well as some plant extracts of plants such as bromelain from pineapple trees, onions White (Allium sativum), onions (Allium cepa)) and the substance of lentinan derived from shiitake mushroom from Japan.

             

  LIVER CANCER CHEMOTHERAPY DRUGS.

•  Zadaxin.
•  Doxorubicin.
• Methotrexate.
• 5FU.
• Cisplatin.
• Colchicine, for liver cancer prevention patients with end-stage hepatitis

GANKYRIN AS A TARGET OF ANTI- LIVER CANCER DRUG 

Gankyrin → as a cofactor that enhances the activity of MDM2 and p53.

Gankyrin binds to Rb and the S6 ATPase subunit in the 26s proteosome.

Gankyrin also binds to Cdk4 and prevents the inhibition of tumor supressor.

p53 has anti-proliferative effects, including apoptosis.

Gankyrin decreased p53 → → degraded cells continue to divide uncontrollably

Drug delivery in the body is divided into 4 :

•  Absorption.

•  Distribution.

•  Metabolism.

•  Excretion.

Drug interactions may occur through the process of delivery as a result of endogenous and exogenous factors.

Liver Cancer

Liver is formed of several cell types. This is what causes the presence of several types "Malignant tumors and benign" tumor.

 Liver function :

• Role in the process of metabolism and absorption of nutrient.
• Produces bile to breakdown fats Stores nutrients, like fats, carbohydrates, and protein.
• Produce substances that play a role in blood clotting during injured . 
• Detoxification and cleansing the body from harmful substances.

Cancer caused by uncontrolled cell proliferation. Cancer will emerge when normal cells DNA run into damage causing genetic mutations. Liver cancer is a malignant tumor, either the network itself (primary liver cancer) or secondary liver cancer can spread to other body parts. Main function of  Liver is As filters toxins and other wastes in the blood. However, when cancer attacks the liver, the liver does not have such capabilities.

Causes of liver cancer are :

• Consuming too much alcohol.
• Cirrhosis.
• Free radicals.
• Carcinogens: substances who can cause cancer growth. In addition there are carcinogens that are pro-carcinogens alter the chemical so it is a trigger cancer.
• Virus
• Food preservatives such as formaldehyde as a preservative meatballs or tofu, the use of textile dyes (not for food) as yellow methanyl on crackers, tofu etc. and Rhodamin, red in the syrup according to the study may also stimulate the onset of liver cancer. Food contamination by aflatoxin.
• Sleeping too late.
• Initiation : Carcinogen cause genetic changes or damage the DNA of normal cells.
• Promotion : Initiated cells become agents that increase its growth into a larger mass of cells function. As a result of being attacked or disrupted tissue.