Abstract
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can result from hepatitis C virus (HCV)-related liver disease and is the fastest-growing cause of cancer-related death in the United States. α-fetoprotein (AFP) has been used as a prognostic factor for HCC, but the value of AFP as a prognostic factor for HCV-related HCC in the United States is unknown. We investigated whether higher levels of AFP at the time of diagnosis are associated with increased mortality of patients with HCV-related HCC.
METHODS: In a retrospective study, we collected data from a cohort of HCV-infected veterans, identifying incident HCC cases from October 1, 1998, to January 1, 2007 (n = 1480 patients). The mean serum levels of AFP, obtained within 60 days before to 30 days after HCC diagnosis, were determined for 1064 patients and categorized as less than 10 ng/mL (18%), 10 to less than 100 ng/mL (30%), 100 to less than 1000 ng/mL (22%), or 1000 ng/mL or more (29%). Cox proportional hazard models were used to associate serum levels of AFP with mortality, adjusting for demographic features, clinical factors, and treatment.
RESULTS: The median survival times were significantly lower among patients with higher levels of AFP: 709 days for patients with less than 10 ng/mL, 422 days for patients with 10 to less than 100 ng/mL, 208 days for patients with 100 to less than 1000 ng/mL, and 68 days for patients with 1000 ng/mL or more. In the multivariate analysis, increased levels of AFP (10 to <100, 100 to <1000, and ≥1000) were associated significantly with increased mortality, compared with a serum AFP level of less than 10; hazard ratios were 1.50, 2.23, and 4.35, respectively.
CONCLUSIONS: Serum AFP level at the time of diagnosis with HCV-related HCC is an independent predictor of mortality.
REF: Clin Gastroenterol Hepatol. 2011 Nov;9(11):989-94. Epub 2011 Aug 4.
Showing posts with label alpha fetoprotein. Show all posts
Showing posts with label alpha fetoprotein. Show all posts
Thursday
Elevated Serum Levels of IGF- binding protein 2 (IGFBP-2) in patients with non-seminomatous germ cell cancer - Correlation with tumor markers Alpha-Fe
Background/Aims:
Alterations of the IGF-system have been described in different types of cancer. However, no information is available about the role of the IGF-system in patients with non-seminomatous germ cell cancer.
Methods:
Free IGF-I, IGF-II, acid-labile subunit and IGFBP-1 to -4 were analyzed by specific radioimmunoassays in 32 patients with untreated non-seminomatous germ cell cancer and compared to IGFBP-levels of 38 healthy controls. Serum-IGFBPs were analyzed by western ligand- and imuno - blotting. In 16 patients, IGFBP-profiles were measured before, during and after treatment.
Results:
In patients with non-seminomas, IGF-II levels were on average 1.44-fold higher than in the healthy control group (1027±48 vs. 711±30 ng/ml, P<0.0001). IGFBP-2 levels were on average 2.6 - fold higher (586±58 ng/ml vs. 226±17 ng/ml, P<0.001). During follow up, a decrease in IGFBP-2 levels was observed in all successfully treated patients, which correlated closely with the decrease of the tumor markers Alpha Fetoprotein (AFP) and Human Chorionic Gonadotropin (HCG). Additionally, in all patients with recurrent disease, a significant further increase of IGFBP-2-levels (from 358±97 ng/ml to 976±260 ng/ml) was detected. IGFBP-3 levels, as measured by RIA, were not different in patients with testicular cancer compared to controls. However, WLB-analysis demonstrated markedly decreased intact IGFBP-3 bands in untreated patients and a significant increase after successful therapy.
Conclusion:
Our results demonstrate markedly elevated IGF-II and IGFBP-2 serum levels in non-seminoma patients, showing a significant decrease after successful therapy and an increase in recurrent disease. Additionally, indirect evidence points to an increased proteolytic activity for IGFBP-3 in untreated testicular cancer patients.
Alterations of the IGF-system have been described in different types of cancer. However, no information is available about the role of the IGF-system in patients with non-seminomatous germ cell cancer.
Methods:
Free IGF-I, IGF-II, acid-labile subunit and IGFBP-1 to -4 were analyzed by specific radioimmunoassays in 32 patients with untreated non-seminomatous germ cell cancer and compared to IGFBP-levels of 38 healthy controls. Serum-IGFBPs were analyzed by western ligand- and imuno - blotting. In 16 patients, IGFBP-profiles were measured before, during and after treatment.
Results:
In patients with non-seminomas, IGF-II levels were on average 1.44-fold higher than in the healthy control group (1027±48 vs. 711±30 ng/ml, P<0.0001). IGFBP-2 levels were on average 2.6 - fold higher (586±58 ng/ml vs. 226±17 ng/ml, P<0.001). During follow up, a decrease in IGFBP-2 levels was observed in all successfully treated patients, which correlated closely with the decrease of the tumor markers Alpha Fetoprotein (AFP) and Human Chorionic Gonadotropin (HCG). Additionally, in all patients with recurrent disease, a significant further increase of IGFBP-2-levels (from 358±97 ng/ml to 976±260 ng/ml) was detected. IGFBP-3 levels, as measured by RIA, were not different in patients with testicular cancer compared to controls. However, WLB-analysis demonstrated markedly decreased intact IGFBP-3 bands in untreated patients and a significant increase after successful therapy.
Conclusion:
Our results demonstrate markedly elevated IGF-II and IGFBP-2 serum levels in non-seminoma patients, showing a significant decrease after successful therapy and an increase in recurrent disease. Additionally, indirect evidence points to an increased proteolytic activity for IGFBP-3 in untreated testicular cancer patients.
Tuesday
Targeting alpha-fetoprotein represses the proliferation of hepatoma cells via regulation of the cell cycle
Background
alpha fetoprotein (AFP) is a biomarker for primary liver cancer, yet little is known about its effect in the pathogenesis of hepatoma. We examined how AFP modulates the proliferation of hepatoma cells.
Methods
Recombinant adenovirus expressing siRNA against alpha fetoprotein (AFP) was created. The repression of cell proliferation in vitro and growth of hepatoma in vivo were examined by colony formation assay and tumor xenograft in SCID mice, respectively. Cell cycle was assayed by flow cytometry. Expression profile was determined by microarrays.
Results
siRNA targeting reduced expression of alpha fetoprotein (AFP) specifically and markedly inhibited the proliferation of hepatoma cells. Local treatment using Adv-AFPsiRNA caused significant repression of the growth of hepatoma derived HepG2 cells in xenograft in SCID mice. Knockdown of AFP resulted in an obvious delay in the G1/S transition of cell cycle, but did not affect apoptosis in HepG2 cells. Some genes related to the cell cycle, including SKP2, Cyclin D1, Csk and EBAG9 were identified.
Conclusions
The endogenous alpha fetoprotein (AFP) is a critical determinant of the growth of hepatoma cells, which functions by regulating the cell cycle. This study suggests that targeting of AFP with siRNA could be a potential therapeutic approach for hepatoma.
ARTICLE
alpha fetoprotein (AFP) is a biomarker for primary liver cancer, yet little is known about its effect in the pathogenesis of hepatoma. We examined how AFP modulates the proliferation of hepatoma cells.
Methods
Recombinant adenovirus expressing siRNA against alpha fetoprotein (AFP) was created. The repression of cell proliferation in vitro and growth of hepatoma in vivo were examined by colony formation assay and tumor xenograft in SCID mice, respectively. Cell cycle was assayed by flow cytometry. Expression profile was determined by microarrays.
Results
siRNA targeting reduced expression of alpha fetoprotein (AFP) specifically and markedly inhibited the proliferation of hepatoma cells. Local treatment using Adv-AFPsiRNA caused significant repression of the growth of hepatoma derived HepG2 cells in xenograft in SCID mice. Knockdown of AFP resulted in an obvious delay in the G1/S transition of cell cycle, but did not affect apoptosis in HepG2 cells. Some genes related to the cell cycle, including SKP2, Cyclin D1, Csk and EBAG9 were identified.
Conclusions
The endogenous alpha fetoprotein (AFP) is a critical determinant of the growth of hepatoma cells, which functions by regulating the cell cycle. This study suggests that targeting of AFP with siRNA could be a potential therapeutic approach for hepatoma.
ARTICLE
Monday
Serum alpha-fetoprotein (AFP) levels in breastfed infants with prolonged indirect hyperbilirubinemia
Abstract
The aim of this prospective study was to verify normal serum alpha-fetoprotein (AFP) levels in jaundiced breastfed infants with indirect hyperbilirubinemia.
Methods
The study was conducted in clinically jaundiced breastfed infants, 20, or more, days old, referred to our outpatient ambulatory. Inclusion criteria were: birth at term after a physiologic pregnancy, with an Apgar score > 7 at 1 and 5 min, no evidence of congenital anomalies or diseases, direct bilirubin < 1 mg/dl, normal values of alpha-1-antitrypsin, glucose-6-phosphate dehydrogenase, thyroid stimulating hormone, triiodothyronine, tyroxine, and normal growth. 30 non-jaundiced breastfed infants age–weight-matched, were used as control group.
Results
98 jaundiced breastfed infants satisfied inclusion criteria. Their mean serum concentration of AFP was significantly higher than control infants (3548 vs 1095 ng/ml, p < 0.001). Serum AFP levels of jaundiced infants were directly associated with serum indirect bilirubin and γ-glutamyltranspeptidase concentrations.
Conclusions
The most probable explanation of elevated AFP in jaundiced breastfed infants may be the presence in human milk of one or more factors which affect hepatocyte growth and/or function. Based on our finding we demonstrated that in jaundiced breastfed infants normal range of serum AFP levels are higher than previously published data for healthy infants. Our data can be useful for a right interpretation of AFP levels in breastfed infants with prolonged jaundiced and may be used to avoid unnecessary investigations.
Rosa Manganaroa, Lucia Marsegliaa, Carmelo Mamìa, Giuseppe Saittaa, Romana Garganob and Marina Gemellia, ,
ARTICLE
The aim of this prospective study was to verify normal serum alpha-fetoprotein (AFP) levels in jaundiced breastfed infants with indirect hyperbilirubinemia.
Methods
The study was conducted in clinically jaundiced breastfed infants, 20, or more, days old, referred to our outpatient ambulatory. Inclusion criteria were: birth at term after a physiologic pregnancy, with an Apgar score > 7 at 1 and 5 min, no evidence of congenital anomalies or diseases, direct bilirubin < 1 mg/dl, normal values of alpha-1-antitrypsin, glucose-6-phosphate dehydrogenase, thyroid stimulating hormone, triiodothyronine, tyroxine, and normal growth. 30 non-jaundiced breastfed infants age–weight-matched, were used as control group.
Results
98 jaundiced breastfed infants satisfied inclusion criteria. Their mean serum concentration of AFP was significantly higher than control infants (3548 vs 1095 ng/ml, p < 0.001). Serum AFP levels of jaundiced infants were directly associated with serum indirect bilirubin and γ-glutamyltranspeptidase concentrations.
Conclusions
The most probable explanation of elevated AFP in jaundiced breastfed infants may be the presence in human milk of one or more factors which affect hepatocyte growth and/or function. Based on our finding we demonstrated that in jaundiced breastfed infants normal range of serum AFP levels are higher than previously published data for healthy infants. Our data can be useful for a right interpretation of AFP levels in breastfed infants with prolonged jaundiced and may be used to avoid unnecessary investigations.
Rosa Manganaroa, Lucia Marsegliaa, Carmelo Mamìa, Giuseppe Saittaa, Romana Garganob and Marina Gemellia, ,
ARTICLE
Wednesday
ANENCEPHALY - Birth Defect
What is Anencephaly?
Anencephaly is a defect in the closure of the neural tube during fetal development. The neural tube is a narrow channel that folds and closes between the 3rd and 4th weeks of pregnancy to form the brain and spinal cord of the embryo. Anencephaly occurs when the "cephalic" or head end of the neural tube fails to close, resulting in the absence of a major portion of the brain, skull, and scalp. Infants with this disorder are born without a forebrain (the front part of the brain) and a cerebrum (the thinking and coordinating part of the brain). The remaining brain tissue is often exposed--not covered by bone or skin. A baby born with anencephaly is usually blind, deaf, unconscious, and unable to feel pain. Although some individuals with anencephaly may be born with a rudimentary brain stem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining consciousness. Reflex actions such as breathing and responses to sound or touch may occur.
An alpha-fetoprotein (AFP) blood test checks the level of AFP in a pregnant woman's blood. AFP is a substance made in the liver of a unborn baby (fetus). The amount of AFP in the blood of a pregnant woman can help see whether the baby may have such problems as spina bifida and anencephaly. An AFP test can also be done as part of a screening test to find other chromosomal problems, such as Down syndrome (trisomy 21) or Edward syndrome (trisomy 18). An AFP test can find an omphalocele, a congenital problem in which some of the baby's intestines stick out through the belly wall.
Normally, low levels of AFP can be found in the blood of a pregnant woman. No AFP (or only a very low level) is generally found in the blood of healthy men or healthy, nonpregnant women.
Anencephaly is a defect in the closure of the neural tube during fetal development. The neural tube is a narrow channel that folds and closes between the 3rd and 4th weeks of pregnancy to form the brain and spinal cord of the embryo. Anencephaly occurs when the "cephalic" or head end of the neural tube fails to close, resulting in the absence of a major portion of the brain, skull, and scalp. Infants with this disorder are born without a forebrain (the front part of the brain) and a cerebrum (the thinking and coordinating part of the brain). The remaining brain tissue is often exposed--not covered by bone or skin. A baby born with anencephaly is usually blind, deaf, unconscious, and unable to feel pain. Although some individuals with anencephaly may be born with a rudimentary brain stem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining consciousness. Reflex actions such as breathing and responses to sound or touch may occur.
An alpha-fetoprotein (AFP) blood test checks the level of AFP in a pregnant woman's blood. AFP is a substance made in the liver of a unborn baby (fetus). The amount of AFP in the blood of a pregnant woman can help see whether the baby may have such problems as spina bifida and anencephaly. An AFP test can also be done as part of a screening test to find other chromosomal problems, such as Down syndrome (trisomy 21) or Edward syndrome (trisomy 18). An AFP test can find an omphalocele, a congenital problem in which some of the baby's intestines stick out through the belly wall.
Normally, low levels of AFP can be found in the blood of a pregnant woman. No AFP (or only a very low level) is generally found in the blood of healthy men or healthy, nonpregnant women.
Monday
Single nucleotide polymorphism in the promoter region of human alpha-fetoprotein (AFP) gene and its significance in hepatocellular carcinoma (HCC)
Variations of serum alpha fetoprotein afp levels in hepatocellular carcinoma patients and cell lines are likely due to the differential activity of enhancer/silencer elements that control AFP. To understand the potential mechanism underlying the differential expression of AFP, we have examined the sequence of the AFP promoter in HCC.
Results
Three novel SNPs in the promoter region of the AFP gene , which have not been previously reported, were found at positions −330, −401 and −692. The level of serum alpha fetoprotein was significantly higher in HCC patients with the CT genotype of 330 SNP or the AG genotype of the 401 SNP. The genotype of CG in 692 SNP was also associated with a significant elevated level of serum alpha fetoprotein , and further this genotype appeared to be associated with the high risk of HCC development. 401 SNP and 692 SNP were located at the positions of known binding sites for transcription factors that have a role in the production of alpha fetoprotein and the growth of tumors .
Conclusions
The novel polymorphisms identified in the promoter region of the AFP gene may be pathologically significant in HCC.
Department of Surgery, The Chinese University of Hong Kong , Prince of Wales Hospital, Shatin, New Territories, Hong Kong
Results
Three novel SNPs in the promoter region of the AFP gene , which have not been previously reported, were found at positions −330, −401 and −692. The level of serum alpha fetoprotein was significantly higher in HCC patients with the CT genotype of 330 SNP or the AG genotype of the 401 SNP. The genotype of CG in 692 SNP was also associated with a significant elevated level of serum alpha fetoprotein , and further this genotype appeared to be associated with the high risk of HCC development. 401 SNP and 692 SNP were located at the positions of known binding sites for transcription factors that have a role in the production of alpha fetoprotein and the growth of tumors .
Conclusions
The novel polymorphisms identified in the promoter region of the AFP gene may be pathologically significant in HCC.
Department of Surgery, The Chinese University of Hong Kong , Prince of Wales Hospital, Shatin, New Territories, Hong Kong
Thursday
Pediatric liver tumors: Initial presentation, image finding and outcome
Results: Hepatocellular carcinoma (HCC) with 91% hepatitis B virus-related, constituted 23 of 33 primary malignant liver tumors and had the poorest survival rate. Initially, 70% of patients with primary malignant liver tumors were at disseminated stages. All of HCC and 88% of hepatoblastoma had elevated serum levels of alpha fetoprotein. However, abnormal liver function tests as alanine aminotransferase , total bilirubin , albumin and alkaline phosphatase were uncommon in patients with pediatric liver tumors. Metastatic liver tumors compared with primary malignant liver tumors showed hypo-echogenicity in abdominal ultrasound (US) exam and a lesser presence of vessel invasion and contrast enhancement in computed tomography studies (P < 0.01).
Conclusions: It is important to diagnose primary malignant liver tumors before their clinical symptoms and signs develop. Children with chronic hepatitis B virus infection must be followed every 6 months by serum alpha-fetoprotein and abdominal US even when their liver function tests are normal. Image studies with abdominal US and computed tomography scan can differentiate between primary and metastatic liver tumors . Background and Methodology in their abstract by: JIAAN-DER WANG, TE-KAU CHANG, HOU-CHUAN CHEN, SHENG-LING JAN, FANG-LIANG HUANG, CHING-SHIANG CHI, CHIEH-CHUNG LIN (2007) Pediatric liver tumors: Departments of Pediatrics and Pediatric Surgery, Taichung Veterans General Hospital and Institute of Clinical Medicine, Chung Shan Medical University , Taichung, Taiwan
Conclusions: It is important to diagnose primary malignant liver tumors before their clinical symptoms and signs develop. Children with chronic hepatitis B virus infection must be followed every 6 months by serum alpha-fetoprotein and abdominal US even when their liver function tests are normal. Image studies with abdominal US and computed tomography scan can differentiate between primary and metastatic liver tumors . Background and Methodology in their abstract by: JIAAN-DER WANG, TE-KAU CHANG, HOU-CHUAN CHEN, SHENG-LING JAN, FANG-LIANG HUANG, CHING-SHIANG CHI, CHIEH-CHUNG LIN (2007) Pediatric liver tumors: Departments of Pediatrics and Pediatric Surgery, Taichung Veterans General Hospital and Institute of Clinical Medicine, Chung Shan Medical University , Taichung, Taiwan
Monday
Human Alpha Fetoprotein not AFP Apple Filing Protocol
I know this is a burning question that everyone has on their mind such as where does AFP come from, what is it exactly and I'm not talking about "Apple Filing Protocol" but alpha fetoprotein AFP which is protein used in a number of blood tests for screening.
Lee Biosolutions is a major supplier of tumor markers such as alpha fetoprotein for the clinical diagnostic . We also specialize in the development and purification of cardiac markers , tumor markers , acute phase proteins , coagulation proteins and immunoassay biomarkers .
Now What is AFP exactly? Human AFP , is a major serum protein of 590 amino acids and a carbohydrate moiety that is normally produced by the fetal yolk sac, the fetal gastrointestinal tract, and eventually by the fetal liver. Alpha-fetoprotein (AFP) has a molecular weight of about 69 kDa. According to an article in Tumor Biology there have been at least 4 subfractions expressing different epitopes that were found in native alpha fetoprotein.
Published reports indicate that alpha-fetoprotein (AFP) , expression in adults is often associated with hepatoma or teratoma . The protein is thought to be the fetal counterpart of serum albumin. The alpha-fetoprotein (AFP) , and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. In addition Alpha fetoprotein binds copper, nickel, fatty acids and bilirubin . The level of alpha fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. Expression has been documented in human adrenal, liver, ovary, testis, and pancreas .
According to WebMDonline an alpha-fetoprotein (AFP) blood test is used to check the level of AFP in a pregnant woman's blood to help see whether the baby may have such problems as spina bifida or anencephaly and chromosomal problems, such as Down syndrome (trisomy 21) or Edward syndrome (trisomy 18).
According to the American Pregnancy association the Triple Test is to determine any potential genetic disorders. The triple test involves testing for Alpha feto protein , Human chorionic gonadotropin (HCG) and unconjugated estriol.
Lee Biosolutions is a major supplier of tumor markers such as alpha fetoprotein for the clinical diagnostic . We also specialize in the development and purification of cardiac markers , tumor markers , acute phase proteins , coagulation proteins and immunoassay biomarkers .
Now What is AFP exactly? Human AFP , is a major serum protein of 590 amino acids and a carbohydrate moiety that is normally produced by the fetal yolk sac, the fetal gastrointestinal tract, and eventually by the fetal liver. Alpha-fetoprotein (AFP) has a molecular weight of about 69 kDa. According to an article in Tumor Biology there have been at least 4 subfractions expressing different epitopes that were found in native alpha fetoprotein.
Published reports indicate that alpha-fetoprotein (AFP) , expression in adults is often associated with hepatoma or teratoma . The protein is thought to be the fetal counterpart of serum albumin. The alpha-fetoprotein (AFP) , and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. In addition Alpha fetoprotein binds copper, nickel, fatty acids and bilirubin . The level of alpha fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. Expression has been documented in human adrenal, liver, ovary, testis, and pancreas .
According to WebMDonline an alpha-fetoprotein (AFP) blood test is used to check the level of AFP in a pregnant woman's blood to help see whether the baby may have such problems as spina bifida or anencephaly and chromosomal problems, such as Down syndrome (trisomy 21) or Edward syndrome (trisomy 18).
According to the American Pregnancy association the Triple Test is to determine any potential genetic disorders. The triple test involves testing for Alpha feto protein , Human chorionic gonadotropin (HCG) and unconjugated estriol.
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