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Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation or for controlling binding of calcium in bones and other tissues. The complete synthesis involves final modification of these so-called "Gla proteins" by the enzyme gamma-glutamyl carboxylase that uses vitamin K as a cofactor. The presence of uncarboxylated proteins indicates a vitamin K deficiency. Carboxylation allows them to bind (chelate) calcium ions, which they cannot do otherwise. Without vitamin K, blood coagulation is seriously impaired, and uncontrolled bleeding occurs. Research suggests that deficiency of vitamin K may also weaken bones, potentially contributing to osteoporosis, and may promote calcification of arteries and other soft tissues.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis.
Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene. The AFP gene is located on the q arm of chromosome 4 (4q25). Maternal AFP serum level is used to screen for Down syndrome, neural tube defects, and other chromosomal abnormalities.
Liver tumors are abnormal growth of liver cells on or in the liver. Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. Liver tumors can be classified as benign (non-cancerous) or malignant (cancerous) growths. They may be discovered on medical imaging, and the diagnosis is often confirmed with liver biopsy. Signs and symptoms of liver masses vary from being asymptomatic to patients presenting with an abdominal mass, hepatomegaly, abdominal pain, jaundice, or some other liver dysfunction. Treatment varies and is highly specific to the type of liver tumor.
Hepatoblastoma is a malignant liver cancer occurring in infants and children and composed of tissue resembling fetal liver cells, mature liver cells, or bile duct cells. They usually present with an abdominal mass. The disease is most commonly diagnosed during a child's first three years of life. Alpha-fetoprotein (AFP) levels are commonly elevated, but when AFP is not elevated at diagnosis the prognosis is poor.
African iron overload, also known as, is an iron overload disorder first observed among people of African descent in Southern Africa and Central Africa. Dietary iron overload is the consumption of large amount of home-brewed beer with high amount of iron content in it. Preparing beer in iron pots or drums results in high iron content. The iron content in home-brewed beer is around 46–82 mg/l compared to 0.5 mg/l in commercial beer. Dietary overload was prevalent in both the rural and urban Black African population, with the introduction of commercial beer in urban areas, the condition has decreased. However, the condition is still common in rural areas. Until recently, studies have shown that genetics might play a role in this disorder. Combination of excess iron and functional changes in ferroportin seems to be the probable cause. This disorder can be treated with phlebotomy therapy or therapy.
In oncology, AFP-L3 is an isoform of Alpha-fetoprotein (AFP), a substance typically used in the triple test during pregnancy and for screening chronic liver disease patients for hepatocellular carcinoma (HCC). AFP can be fractionated by affinity electrophoresis into 3 glycoforms: L1, L2, and L3 based on the reactivity with the lectin Lens culinaris agglutinin (LCA). AFP-L3 binds strongly to LCA via an additional α 1-6 fucose residue attached at the reducing terminus of N-acetylglucosamine; this is in contrast to the L1 isoform. It is the L1 isoform which is typically associated with non-HCC inflammation of liver disease condition. The L3 isoform is specific to malignant tumors and its detected presence can serve to identify patients whom need increased monitoring for the development of HCC in high risk populations. AFP-L3% is now being considered as a tumor marker for the North American demographic.
Sorafenib, is a kinase inhibitor drug approved for the treatment of primary kidney cancer, advanced primary liver cancer, FLT3-ITD positive AML and radioactive iodine resistant advanced thyroid carcinoma.
In histopathology, a Mallory body, Mallory-Denk body, and Mallory's hyaline, is an inclusion found in the cytoplasm of liver cells. Mallory bodies are damaged intermediate filaments within the liver cells.
Carboxylation is a chemical reaction in which a carboxylic acid group is produced by treating a substrate with carbon dioxide. The opposite reaction is decarboxylation. In chemistry, the term carbonation is sometimes used synonymously with carboxylation, especially when applied to the reaction of carbanionic reagents with CO2. More generally, carbonation usually describes the production of carbonates.
Gamma-glutamyl carboxylase is an enzyme that in humans is encoded by the GGCX gene, located on chromosome 2 at 2p12.
Liver cancer is cancer that starts in the liver. Liver cancer can be primary or secondary. Liver metastasis is more common than that which starts in the liver. Liver cancer is increasing globally.
Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain is a protein domain that contains post-translational modifications of many glutamate residues by vitamin K-dependent carboxylation to form γ-carboxyglutamate (Gla). Proteins with this domain are known informally as Gla proteins. The Gla residues are responsible for the high-affinity binding of calcium ions.
Glypican-3 is a protein that, in humans, is encoded by the GPC3 gene. The GPC3 gene is located on human X chromosome (Xq26) where the most common gene encodes a 70-kDa core protein with 580 amino acids. Three variants have been detected that encode alternatively spliced forms termed Isoforms 1 (NP_001158089), Isoform 3 (NP_001158090) and Isoform 4 (NP_001158091).
Golgi membrane protein 1 (GOLM1) also known as Golgi phosphoprotein 2 or Golgi membrane protein GP73 is a protein that in humans is encoded by the GOLM1 gene. Two alternatively spliced transcript variants encoding the same protein have been described for this gene.
Epithelial membrane protein 3 (EMP3) is a trans-membrane signaling molecule that is encoded by the myelin-related gene EMP3. EMP3 is a member of the peripheral myelin protein gene family 22-kDa (PMP22), which is mainly responsible for the formation of the sheath of compact myelin. Although the detailed functions and mechanisms of EMP3 still remain unclear, it is suggested that EMP3 is possibly epigenetically linked to certain carcinomas.
Fibrolamellar hepatocellular carcinoma (FHCC) is a rare form of hepatocellular carcinoma (HCC) that typically affects young adults and is characterized, under the microscope, by laminated fibrous layers interspersed between the tumour cells. Approximately 200 new cases are diagnosed worldwide each year.
In transplantation medicine, the Milan criteria are set of criteria applied in consideration of patients with cirrhosis and hepatocellular carcinoma (HCC) for liver transplantation with intent to cure their disease. Their significance derives from a landmark 1996 study in 48 patients by Mazzaferro et al which showed that selecting cases for transplantation according to specific strict criteria led to improved overall and disease-free survival at a 4-year time point. These same criteria have since been adopted by the Organ Procurement and Transplantation Network (OPTN) in the evaluation of patients for potential transplantation.
Elevated alpha-fetoprotein refers to a state where alpha-fetoprotein levels are outside of the reference range.
Patrizia Paterlini-Bréchot, born in the Italian city of Reggio Emilia, is an Italian scientist and a professor of cell biology and oncology working at the Faculté de Médecine Necker-Enfants Malades, Université Paris Descartes and at INSERM in Paris.
References
- ↑ Liebman HA, Furie BC, Tong MJ, et al. (1984). "Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma". N. Engl. J. Med. 310 (22): 1427–31. doi:10.1056/NEJM198405313102204. PMID 6201741.
- ↑ Tsai SL, Huang GT, Yang PM, Sheu JC, Sung JL, Chen DS (1990). "Plasma des-gamma-carboxyprothrombin in the early stage of hepatocellular carcinoma". Hepatology. 11 (3): 481–8. doi:10.1002/hep.1840110321. PMID 2155866.
- ↑ Cui R, Wang B, Ding H, Shen H, Li Y, Chen X (2002). "Usefulness of determining a protein induced by vitamin K absence in detection of hepatocellular carcinoma". Chin. Med. J. 115 (1): 42–5. PMID 11930656.
- 1 2 Marrero JA, Su GL, Wei W, et al. (2003). "Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients". Hepatology. 37 (5): 1114–21. doi: 10.1053/jhep.2003.50195 . PMID 12717392.
- ↑ Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA (2007). "Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3". Cancer Biomark. 3 (2): 79–87. PMID 17522429.
- ↑ Lamerz R, Runge M, Stieber P, Meissner E (1999). "Use of serum PIVKA-II (DCP) determination for differentiation between benign and malignant liver diseases". Anticancer Res. 19 (4A): 2489–93. PMID 10470180.
- ↑ Ertle, JM; Heider, D; Wichert, M; Keller, B; Kueper, R; Hilgard, P; Gerken, G; Schlaak, JF (2013). "A combination of α-fetoprotein and des-γ-carboxy prothrombin is superior in detection of hepatocellular carcinoma". Digestion. 87 (2): 121–31. doi:10.1159/000346080. PMID 23406785.
- ↑ Lefrere JJ, Gozin D (1987). "Use of des-gamma-carboxyprothrombin in retrospective diagnosis of hidden intoxication of anticoagulants". J. Clin. Pathol. 40 (5): 589. doi:10.1136/jcp.40.5.589-b. PMC 1141034 . PMID 3584512.