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Sample records for alpha-fetoprotein afp stem

  1. ALPHA-FETOPROTEIN (AFP), STEM CELLS, AND CANCER: HOW STUDY OF THE PRODUCTION OF AFP DURING CHEMICAL HEPATOCARCINOGENESIS LED TO REAFFIRMATION OF THE STEM CELL THEORY OF CANCER

    PubMed Central

    Sell, Stewart

    2008-01-01

    Identification of the cells in the liver that produce alpha-fetoprotein (AFP) during development, in response to liver injury, and during the early stages of chemical hepatocarcinogenesis led to the conclusion that maturation arrest of liver-determined tissue stem cells was the cellular process that gives rise to hepatocellular carcinomas (HCC). When the cellular changes in these processes were compared that of the formation of teratocarcinomas, the hypothesis arose that all cancers arise from maturation arrest of tissue determined stem cells. This was essentially a reinterpretation of the embryonal rest theory of cancer whereby tissue stem cells take the role of embryonal rests. A corollary of the stem cell theory of the origin of cancer is that cancers contain the same functional cell populations as do normal tissues: stem cells, transit-amplifying cells, and mature cells. Cancer stem cells retain the essential feature of normal stem cells: the ability to self-renew. Growth of cancers is due to continued proliferation of cancer transit-amplifying cells that do not differentiate to mature cells (maturation arrest). On the other hand, cancer stem cells generally divide very rarely and contribute little to tumor growth. However, the presence of cancer stem cells in tumors is believed to be responsible for the properties of immortalization, transplantability and resistance to therapy characteristic of cancers. Current therapies for cancer (chemotherapy, radiotherapy, anti-angiogenesis and differentiation therapy) are directed against the cancer transit amplifying cells. When these therapies are discontinued, the cancer re-forms from the cancer stem cells. Therapy directed toward interruption of the cell-signaling pathways that maintain cancer stem cells could lead to new modalities to the prevention of re-growth of the cancer. PMID:18612221

  2. Alpha-fetoprotein (AFP)-derived peptides as epitopes for hepatoma immunotherapy: a commentary.

    PubMed

    Mizejewski, Gerald J

    2009-02-01

    The various immunological roles of human alpha-fetoprotein (HAFP), and its correlation with hepatomas, that is, hepatocellular carcinomas (HCCs), are not often addressed together in biomedical reports considering that HAFP is an established biomarker for hepatomas. Studies reporting measurement of HAFP serum levels in hepatoma patients in basic/clinical research settings has greatly increased over the years. Recent reports have now expanded our base knowledge in the mounting of an immune response against AFP, a self antigen, during hepatoma tumorigenesis. Advances in the detection and identification of AFP-derived peptide epitopes are opening new vistas of knowledge regarding the immunological role of AFP-peptides as T cell stimulating antigens in the course of hepatoma growth and progression. The present commentary addresses HAFP-derived peptides as immunologic responders in HCC and their use in the study and generation of AFP-peptide sensitized T cells directed against hepatoma cells. Attempts were further made to relate the AFP-derived peptide epitopes to T cell activities during the course of hepatoma immunotherapies and to profile the traits and properties of the peptides themselves. Hence, the present commentary was divided into two sections; (1) the characterization, properties, and traits of AFP peptide epitopes, and (2) the use of AFP-derived peptides in the therapeutic induction of T cells primed against hepatoma cells using both in vivo and in vitro models.

  3. Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection.

    PubMed

    Bird, Thomas G; Dimitropoulou, Polyxeni; Turner, Rebecca M; Jenks, Sara J; Cusack, Pearce; Hey, Shiying; Blunsum, Andrew; Kelly, Sarah; Sturgeon, Catharine; Hayes, Peter C; Bird, Sheila M

    2016-01-01

    Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009-14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 304 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, 'AFP-detected' tumours were offered potentially curative management as frequently as 'US-detected' HCCs; and had comparable survival. Linearity of serial log10-transformed AFPs in HCC cases and in the screening 'HCC-free' cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p<1.72*10-5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refine-able algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance. PMID:27308823

  4. Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection

    PubMed Central

    Dimitropoulou, Polyxeni; Turner, Rebecca M.; Jenks, Sara J.; Hey, Shiying; Blunsum, Andrew; Kelly, Sarah; Sturgeon, Catharine; Hayes, Peter C.; Bird, Sheila M.

    2016-01-01

    Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009–14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 304 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, ‘AFP-detected’ tumours were offered potentially curative management as frequently as ‘US-detected’ HCCs; and had comparable survival. Linearity of serial log10-transformed AFPs in HCC cases and in the screening ‘HCC-free’ cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p<1.72*10−5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refine-able algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance. PMID:27308823

  5. Hepatoid carcinoma of the pancreas producing protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP).

    PubMed

    Matsueda, Kazuhiro; Yamamoto, Hiroshi; Yoshida, Yasuo; Notohara, Kenji

    2006-10-01

    We describe a rare case of hepatoid carcinoma of the pancreas with production of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP). The patient was a 49-year-old woman admitted because of high serum levels of PIVKA-II (1.63 AU/ml) and AFP (623 ng/ml) and abnormal ultrasonographic findings of the pancreas, found incidentally at medical checkup. Both ultrasonography and computed tomography showed swelling of the pancreas with small areas of low density, but no hepatic lesions. The serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were not increased. A PIVKA-II and AFP-producing pancreatic cancer was strongly suspected, and total pancreatectomy was performed. Pathological examination showed that the tumor cells were arranged in trabecular and solid patterns with bile production, and were immunohistochemically positive for PIVKA-II and AFP, resembling hepatocellular carcinoma cells. The tumor was diagnosed as hepatoid carcinoma of the pancreas, and the patient has survived 48 months after initial diagnosis. It is important that hepatoid carcinoma be considered as a possible malignant tumor of the pancreas, and simultaneous measurement of the serum levels of AFP and PIVKA-II will enable earlier diagnosis. This is the first report describing hepatoid carcinoma of the pancreas producing PIVKA-II.

  6. Expression of human. alpha. -fetoprotein in yeast

    SciTech Connect

    Yamamoto, Ritsu; Sakamoto, Takashi; Nishi, Shinzo; Sakai, Masaharu; Morinaga, Tomonori; Tamaoki, Taiki Univ. of Calgary, Alberta )

    1990-01-01

    Human {alpha}-fetoprotein (AFP) was expressed in Saccharomyces cerevisiae, with a plasmid containing the cDNA sequence for human AFP fused with the rat AFP signal peptide. The recombinant AFP was purified from the yeast lysate by DEAE-cellulose and immunoaffinity chromatography. The amino acid composition and the molecular weight of the recombinant AFP were similar to those of hepatoma AFP. N-terminal amino acids sequence analysis indicated that the signal peptide had been processed. The recombinant and hepatoma AFP reacted identically in Ouchterlony immunodiffusion and radioimmunoassay tests. These observations indicated that the yeast recombinant protein had the properties of native AFP.

  7. Clinical evaluation of serum alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels in patients with hepatocellular carcinoma following interventional radiology.

    PubMed

    Minakuchi, K; Murata, K; Kaminoh, T; Takada, K; Takashima, S; Nakamura, K; Onoyama, Y

    1993-01-01

    Fourteen patients with unrespectable HCC were treated with various interventional radiology (IVR) procedures. The initial therapeutic response was determined using computed tomography (CT) findings, and determinations of serum alpha-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) levels. When CT studies of the initial response to IVR were compared with changes in the serum AFP and PIVKA-II levels, the AFP level was found to correlate more closely than the PIVKA-II levels. The PIVKA-II level correlated more closely than the AFP level in cases with poor response to IVR. Both of these tumor markers should be measured in combination with the diagnostic imagings for follow-up studies of IVR.

  8. A phase II, randomized, controlled trial of S-adenosylmethionine in reducing serum alpha-fetoprotein (AFP) in patients with hepatitis C cirrhosis and elevated AFP

    PubMed Central

    Morgan, Timothy R.; Osann, Kathryn; Bottiglieri, Teodoro; Pimstone, Neville; Hoefs, John C.; Hu, Ke-Qin; Hassanein, Tarek; Boyer, Thomas D.; Kong, Lorene; Chen, Wen-Pin; Richmond, Ellen; Gonzalez, Rachel; Rodriguez, Luz M.; Meyskens, Frank L.

    2015-01-01

    In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC while administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum AFP level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 grams/day, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. 110 subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury, or markers of oxidative stress or antioxidant potential. PMID:26130251

  9. [Alpha Fetoprotein-producing Lung Adenocarcinoma].

    PubMed

    Komori, Kazuyuki; Tabata, Toshiharu; Sato, Kimiaki; Katsumata, Hiroshi; Minowa, Muneo; Kondo, Takashi

    2015-11-01

    We report a case of alpha fetoprotein (AFP) -producing lung adenocarcinoma. A 53-year-old man was referred to our hospital due to right pneumothorax. Computed tomography showed right moderate pneumothorax, a solid tumor in the upper lobe (S3) and mediastinal lymph node swelling. The serum AFP level was as high as 223.0 ng/ml. Frozen examination revealed a low-differentiated adenocarcinoma. Based on the pathological and immunohistochemical findings, the tumor was diagnosed as AFP-producing lung adenocarcinoma.

  10. Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1′-S-1′-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors

    PubMed Central

    Arshad, Norhafiza M.; In, Lionel L.A.; Soh, Tchen Lin; Azmi, Mohamad Nurul; Ibrahim, Halijah; Awang, Khalijah; Dudich, Elena; Tatulov, Eduard; Nagoor, Noor Hasima

    2015-01-01

    Purpose Previous in vitro and in vivo studies have reported that 1′-S-1′-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA. Experimental Design To study the synergistic effect of both agents on human cancer xenografts, athymic nude (Nu/Nu) mice were used and treated with various combination regimes intraperitoneally. Serum levels of tumour markers for carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) were assessed using sandwich ELISA. IHC and Western blotting were also conducted on in vivo tumour biopsies to investigate the involvement of NF-κB regulated genes and inflammatory biomarkers. Quantification and correlation between drug efficacies and AFP-receptors were done using IF-IC and Pearson's correlation analysis. Results Mice exposed to combined treatments displayed higher reductions in tumour volume compared to stand alone agents, consistent with in vitro cytotoxicity assays. Milder signs of systemic toxicity, such as loss in body weight and inflammation of vital organs were also demonstrated compared to stand alone treatments. Tumour marker levels were consistent within all rhAFP/ACA treatment groups where levels of CEA and PSA were initially elevated upon commencement of treatment, and consecutively reduced corresponding to a decrease in tumour bulk volume. Both IHC and Western blotting results indicated that the combined action of rhAFP/ACA was not only able to down-regulate NF-κB activation

  11. A resected case of metachronous liver metastasis from lung cancer producing alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II).

    PubMed

    Oshiro, Yukio; Takada, Yasutsugu; Enomoto, Tsuyoshi; Fukao, Katashi; Ishikawa, Shigemi; Iijima, Tatsuo

    2004-01-01

    A resected case of huge liver metastasis of hepatoid adenocarcinoma of the lung is described. A 77-year-old man who presented a solitary huge liver tumor was admitted to our hospital. He had undergone right lower lobectomy of the lung for lung cancer one year before. The view of imaging studies was not a typical one of hepatocellular carcinoma. Serum levels of AFP and PIVKA-II were 334,500ng/mL and 3,890mAU/mL, respectively, and the proportion of AFP L3 was 97.9%. It was thought that they were strongly diagnostic for hepatocellular carcinoma. Extended right lobectomy of the liver was performed. Microscopically, it was poorly differentiated adenocarcinoma and diagnosed as liver metastasis from the formerly resected lung cancer. The tumor was composed of cells with both sheet-like growth and tubule formation. The neoplastic cells, in the sheet-like growth resembled hepatocellular carcinoma cells. By immunohistochemical staining with anti-AFP and anti-PIVKA-II antibodies, cancer cells of both the primary and metastatic lesions were positive. The patient eventually died of multiple liver and bone metastasis 6 months after the operation.

  12. Protein profiling of alpha-fetoprotein producing gastric adenocarcinoma

    PubMed Central

    He, Liang; Ye, Fei; Qu, Linlin; Wang, Daguang; Cui, Miao; Wei, Chengguo; Xing, Yanpeng; Lee, Peng; Suo, Jian; Zhang, David Y.

    2016-01-01

    Alpha-fetoprotein (AFP) producing gastric adenocarcinoma is considered as a rare subtype of gastric adenocarcinoma. Compared with AFP non-producing gastric adenocarcinoma, our study and other previous studies showed that AFP producing gastric adenocarcinoma is more aggressive and prone to liver metastasis. Using the Protein Pathway Array, 11 of out of 286 proteins tested were found to be differentially expressed between AFP producing (n=32) and AFP non-producing (n=45) gastric adenocarcinoma tissues. In addition, the high level expression of XIAP and IGF-Irβ in gastric adenocarcinoma tissues was independent factors for poor prognosis in AFP producing gastric adenocarcinoma patients. A risk model based on the XIAP and IGF-Irβ expression levels can separate AFP producing gastric adenocarcinoma patients into 2 subgroups and each subgroup had a distinct set of signaling pathways involved. In conclusion, AFP producing gastric adenocarcinoma is a heterogeneous cancer with different clinical outcomes, biological behaviors and underlying molecular alterations. PMID:27057629

  13. Anxiety in women with low maternal serum alpha-fetoprotein screening results.

    PubMed

    Abuelo, D N; Hopmann, M R; Barsel-Bowers, G; Goldstein, A

    1991-06-01

    The purpose of this study was to measure anxiety in pregnant women who had low maternal serum alpha-fetoprotein (MSAFP) screening test levels, received genetic counselling and chose to undergo amniocentesis for fetal chromosome analysis. Their anxiety levels were compared with the levels in women undergoing amniocentesis because of advanced maternal age. The results indicate a higher level of anxiety in women with low alpha-fetoprotein (AFP) levels.

  14. Alpha fetoprotein antagonizes apoptosis induced by paclitaxel in hepatoma cells in vitro.

    PubMed

    Zhu, Mingyue; Li, Wei; Lu, Yan; Dong, Xu; Chen, Yi; Lin, Bo; Xie, Xieju; Guo, Junli; Li, Mengsen

    2016-01-01

    Hepatocellular carcinoma (HCC) cell resistance to the effects of paclitaxel has not been adequately addressed. In this study, we found that paclitaxel significantly inhibited the viability of HLE, Bel 7402 and L-02 cells in a dose- and time-dependent manner. HLE cells and L-02 cells resisted the cytotoxicity of paclitaxel when transfected with pcDNA3.1-afp vectors. However, Bel 7402 cell sensitivity to paclitaxel was increased when transfected with alpha fetoprotein (AFP)-siRNA. Bel 7402 cell resistance to paclitaxel was associated with the expression of the "stemness" markers CD44 and CD133. Paclitaxel significantly inhibited growth and promoted apoptosis in HLE cells and L-02 cells by inducing fragmentation of caspase-3 and inhibiting the expression of Ras and Survivin, but pcDNA3.1-afp vectors prevented these effects. However, paclitaxel could not significantly promote the cleavage of caspase-3 or suppress the expression of Ras and Survivin in Bel 7402 cells. Silenced expression of AFP may be synergistic with paclitaxel to restrain proliferation and induce apoptosis, enhance cleavage of caspase-3, and suppress the expression of Ras and Survivin. Taken together, AFP may be an important molecule acting against paclitaxel-inhibited proliferation and induced apoptosis in HCC cells via repressing the activity of caspase-3 and stimulating the expression of Ras and Survivin. Targeted inhibition of AFP expression after treatment with paclitaxel is an available strategy for the therapy of patients with HCC. PMID:27255186

  15. The efficacy of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) levels in determining the malignancy of solitary pulmonary nodules.

    PubMed

    Bekci, T T; Senol, T; Maden, E

    2009-01-01

    We investigated the utility of the tumour markers carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) for the differential diagnosis of benign and malignant solitary pulmonary nodules in 42 hospitalized patients. Routine medical history and physical examination of each patient was performed and each patient also had a chest X-ray and a thoracic computed tomography scan. The following diagnostic procedures were also undertaken: bronchoscopy, transthoracic needle aspiration biopsy, sputum cytology and culture, analysis of sputum acid-fast bacilli and thoracotomy. Measurement of serum levels of tumour antigens by Immulite 2000 radioimmunoassay found that three tumour markers, CEA, CA125 and CA15-3, could be used in the diagnosis of malignant solitary pulmonary nodules. More research is now required involving a larger group of patients.

  16. Regression of hepatocarcinoma cells using RNA aptamer specific to alpha-fetoprotein

    SciTech Connect

    Lee, Young Ju; Lee, Seong-Wook

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Identification of RNA aptamer specific to AFP with high affinity. Black-Right-Pointing-Pointer Specific induction of HCC proliferation by AFP. Black-Right-Pointing-Pointer Efficient increase in oncogene expression by AFP. Black-Right-Pointing-Pointer Efficient inhibition of AFP-mediated HCC proliferation by the aptamer. Black-Right-Pointing-Pointer Efficient suppression of AFP-induced oncogene expression of by the aptamer. -- Abstract: Alpha-fetoprotein (AFP) is a cancer-associated fetal protein and has long been utilized as a serum fetal defect/tumor marker to monitor distress/disease progression. In addition, AFP is closely associated with the proliferation of hepatocellular carcinoma. Thus, direct targeting of AFP has been recommended for a therapeutic strategy against hepatocellular carcinoma. In this study, we developed and characterized an RNA aptamer that specifically bound to the alpha-fetoprotein using SELEX technology. The aptamer interacted with the AFP with a K{sub D} of {approx}33 nM. Importantly, the identified aptamer specifically and efficiently inhibited the AFP-mediated proliferation of hepatocarcinoma cells in a dose dependent manner. Moreover, the aptamer efficiently down-regulated AFP-induced expression of oncogenes in the cells. These results indicate that an AFP-specific RNA aptamer could be a useful therapeutic and diagnostic agent against AFP-related hepatocellular carcinoma.

  17. Frequency of raised alpha-fetoprotein level among Chinese patients with hepatocellular carcinoma related to hepatitis B and C.

    PubMed

    Tsai, J F; Chang, W Y; Jeng, J E; Ho, M S; Lin, Z Y; Tsai, J H

    1994-06-01

    Antibody to hepatitis C virus (anti-HCV) was found to be an independent risk factor for hepatocellular carcinoma and raised serum alpha-fetoprotein (AFP) level. In addition, the frequency of raised AFP in patients with anti-HCV was higher than in those without (91.5% vs 65.2%, P = 0.0001).

  18. Maternal serum alpha-fetoprotein and fetal triploidy.

    PubMed

    Pircon, R A; Towers, C V; Porto, M; Gocke, S E; Garite, T J

    1989-10-01

    Fetal triploidy is commonly found in early pregnancy. The majority of these pregnancies spontaneously abort in the first trimester. Occasionally, the pregnancy progresses to the second and third trimesters. We reviewed the maternal serum alpha-fetoprotein (MSAFP), amniotic fluid alpha-fetoprotein (AFP), amniotic fluid acetylcholinesterase (ACHE), fetal pathology, and placental pathology in sex second-trimester pregnancies complicated by fetal triploidy. Four of these patients had MSAFP values greater than 7.5 multiples of the median (MoM). Five of six pregnancies had MSAFP values greater than 2.25 MoM. All five of these patients had a partial mole. Four patients had amniotic fluid AFP values greater than 2.0 MoM. Two fetuses had associated neural tube defects. These were the only patients with positive amniotic fluid ACHE. None of the other patients had fetuses with anomalies that are known to be associated with an elevated MSAFP. The elevated MSAFP appeared to be related to the presence of a partial mole. Two of the five cases with an MSAFP greater than 2.25 MoM did not have sonographic evidence of a significant anomaly. Therefore, karyotyping can be of benefit in evaluating patients with elevated MSAFP. PMID:2480590

  19. Hepatic progenitor cells, stem cells, and AFP expression in models of liver injury

    PubMed Central

    Kuhlmann, Wolf D; Peschke, Peter

    2006-01-01

    Adult hepatocytes and liver-cell progenitors play a role in restoring liver tissue after injury. For the study of progenitor cells in liver repair, experimental models included (a) surgical removal of liver tissue by partial hepatectomy; (b) acute injury by carbontetrachloride; (c) acute injury by d-galactosamine (GalN) and N-nitrosomorpholine (NNM); and (d) chemical hepatocarcinogenesis by feeding NNM in low and high doses. Serological and immunohistological detection of alpha-fetoprotein gene expression served to follow pathways of cellular differentiation. Stem cells were not required in models of surgical removal of parenchyma and in carbon tetrachloride intoxication of adult hepatocytes. In contrast, regeneration of liver occurred through biliary epithelial cells in injuries induced by GalN and NNM. These biliary epithelial cells, collectively called oval cells, are most probably derived from the canals of Hering. Proliferating bile duct cells reached a level of differentiation with reactivation of foetal genes and significant alpha-1-fetoprotein (AFP) synthesis signalling a certain degree of retrodifferentiation with potential stemness. Due to the same embryonic origin of bile ducts and hepatocytes, biliary epithelium and its proliferating progeny (oval cells) have a defined role in liver regeneration as a transit and amplification compartment. In their early proliferation stage, oval cells were heavily engaged in DNA synthesis ([3H]thymidine labelling). Pulse-chase experiments during experimental hepatocarcinogenesis exhibited their development into hepatocytes with high risk for transformation and leading to foci of altered hepatocytes. Hepatocellular carcinomas may arise either from proliferating/differentiating oval cells or from adult hepatocytes; both cell types have stem-like properties. AFP-positive and AFP-negative carcinomas occurred in the same liver. They may represent random clonal origin. The heterogeneity of phenotypic marker (AFP) correlated

  20. AFP — EDRN Public Portal

    Cancer.gov

    AFP is a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatoma or teratoma. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin.

  1. Elevated alpha-fetoprotein: differential diagnosis - hepatocellular carcinoma and other disorders.

    PubMed

    Wong, Robert J; Ahmed, Aijaz; Gish, Robert G

    2015-05-01

    The incidence of cirrhosis-related hepatocellular carcinoma (HCC) is rising. Curative surgical options are available; outcomes are acceptable with early diagnosis. Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin (DCP) are HCC risk markers. A high or increasing serum biomarker level can be predictive of the eventual development of HCC, large tumor size, advanced stage, extrahepatic metastases, portal vein thrombosis, and postoperative HCC recurrence. Based on FDA guidelines for HCC risk assessment, clinicians can consider using either the combination of AFP-L3 with DCP, or the combination of AFP-L3 with AFP and DCP. PMID:25921665

  2. Alpha-fetoprotein and its value for predicting pregnancy outcomes – a re-evaluation

    PubMed Central

    Darouich, Ayham Alhaj; Liehr, Thomas; Weise, Anja; Schlembach, Dietmar; Schleußner, Ekkehart; Kiehntopf, Michael; Schreyer, Isolde

    2015-01-01

    Introduction Alpha-fetoprotein (AFP) concentrations can be determined framing others from invasively acquired amnion fluid (AF-AFP). While the biological role of AFP remains unclear it is well known that AFP-levels can be altered in connection with specific clinical and/or genetic alterations of the fetus. Materials and Method here a retrospective study based on 3,119 singleton and 56 twin pregnancies is presented. The standard levels of amnion fluid derived alpha-fetoprotein level (AF-AFP) between 12th and 36th weeks of gestation were determined. Additionally, acetylcholinesterase (AChE) test results for 63 cases, ultrasonography results for 32 cases and abnormal karyotypic findings for 100 cases were available for selected cases. Results and Discussion according to the present data the AF-AFP test is reliable and provides expected test results in terms of population studies. However, individual AF-AFP test results can be subject to high individual variations. In this study AF-AFP multiple of medians (MoM) over 1.7 were indicative for neuronal tube defects and/or omphalocele in only 6.3% of the cases, while such AF-AFP values were hints on severe sonographic signs in 62% of the cases. Also, altered AF-AFP concentrations were present in 82% of cytogenetically abnormal cases. Overall, even though predicative value of the AF-AFP-test is matter of discussion it continues to be widely applied in invasive prenatal diagnostics. This study indicates that it only can be applied reliably in combination with other tests like banding cytogenetics, ultrasonography and all embedded in well-established genetic counseling. PMID:27358693

  3. Amniotic fluid cortisol and alpha-fetoprotein in normal and aneuploid pregnancies.

    PubMed

    Drugan, A; Subramanian, M G; Johnson, M P; Evans, M I

    1988-01-01

    Cortisol and alpha-fetoprotein (AFP) levels were measured in amniotic fluid (AF) samples at 15-20 weeks of gestation from 125 normal pregnancies and 29 pregnancies affected by aneuploidy. The normal pregnancy group was further subdivided into 'low' AF-AFP (less than 0.6 MOM, n = 60) and 'normal' AF-AFP (0.6 less than AFP less than 1.4 MOM, n = 65). A significant, inverse, linear correlation was found between cortisol and AF-AFP for both normal AFP and low AFP groups (r = -0.26, and r = -0.4, respectively, p less than 0.05). Gestational age was significantly correlated with both cortisol and AFP levels in the normal pregnancy groups. No difference was found when cortisol levels were compared between the low and normal AFP groups. The correlation between cortisol and AFP in aneuploid pregnancies was not significant (p = 0.37). The strong association between cortisol or AFP and gestational age in normal pregnancy (p less than 0.00001) was lost in trisomic gestation. We conclude that higher cortisol levels do not seem to be the cause of low AFP in normal or aneuploid pregnancies. PMID:2483963

  4. ZBTB20 is a sequence-specific transcriptional repressor of alpha-fetoprotein gene.

    PubMed

    Zhang, Hai; Cao, Dongmei; Zhou, Luting; Zhang, Ye; Guo, Xiaoqin; Li, Hui; Chen, Yuxia; Spear, Brett T; Wu, Jia-Wei; Xie, Zhifang; Zhang, Weiping J

    2015-07-15

    Alpha-fetoprotein (AFP) represents a classical model system to study developmental gene regulation in mammalian cells. We previously reported that liver ZBTB20 is developmentally regulated and plays a central role in AFP postnatal repression. Here we show that ZBTB20 is a sequence-specific transcriptional repressor of AFP. By ELISA-based DNA-protein binding assay and conventional gel shift assay, we successfully identified a ZBTB20-binding site at -104/-86 of mouse AFP gene, flanked by two HNF1 sites and two C/EBP sites in the proximal promoter. Importantly, mutation of the core sequence in this site fully abolished its binding to ZBTB20 in vitro, as well as the repression of AFP promoter activity by ZBTB20. The unique ZBTB20 site was highly conserved in rat and human AFP genes, but absent in albumin genes. These help to explain the autonomous regulation of albumin and AFP genes in the liver after birth. Furthermore, we demonstrated that transcriptional repression of AFP gene by ZBTB20 was liver-specific. ZBTB20 was dispensable for AFP silencing in other tissues outside liver. Our data define a cognate ZBTB20 site in AFP promoter which mediates the postnatal repression of AFP gene in the liver.

  5. [Engineering of a System for the Production of Mutant Human Alpha-Fetoprotein in the Methylotrophic Yeast Pichia pastoris].

    PubMed

    Morozkina, E V; Vavilova, E A; Zatsepin, S S; Klyachko, E V; Yagudin, T A; Chulkin, A M; Dudich, I V; Semenkova, L N; Churilova, I V; Benevolenskii, S V

    2016-01-01

    A system for the production of mutant recombinant human alpha-fetoprotein (rhAFPO) lacking the glycosylation site has been engineered in the yeast Pichia pastoris. A strain of the methylotrophic yeast Pichia pastoris GS 115/pPICZ?A/rhAFP0, which produces unglycosylated rhAFPO and secretes it to the culture medium, has been constructed. Optimization and scale-up of the fermentation technology have resulted in an increase in the rhAFP0 yield to 20 mg/L. A scheme of isolation and purification of biologically active rhAFP0 has been developed. The synthesized protein has the antitumor activity, which is analogous to the activity of natural human embryonic alpha-fetoprotein.

  6. The immunosuppression role of alpha-fetoprotein in human hepatocellular carcinoma.

    PubMed

    Meng, Wenbo; Bai, Bing; Bai, Zhongtian; Li, Yan; Yue, Ping; Li, Xun; Qiao, Liang

    2016-06-01

    Human hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. Alpha-fetoprotein (AFP) is perhaps the best-defined tumor marker for HCC, and as such, it is widely used in clinical settings as an adjuvant diagnostic and prognostic tool. Up to 70% of HCC cases exhibit elevated serum level of AFP, but its pathophysiological functions in HCC are poorly defined. It is now known that AFP is not just a fetal form of carrier protein and a tumor marker, it is also critically involved in the regulation of several important cellular functions, such as cell growth, differentiation, apoptosis, angiogenesis, and immune regulation. In this mini-review, we summarize the recent development of AFP in hepatocellular carcinoma. PMID:27448785

  7. Alpha-fetoprotein detection by using a localized surface plasmon coupled fluorescence fiber-optic biosensor

    NASA Astrophysics Data System (ADS)

    Chang, Ying-Feng; Chen, Ran-Chou; Li, Ying-Chang; Yu, Chih-Jen; Hsieh, Bao-Yu; Chou, Chien

    2007-11-01

    Alpha-fetoprotein (AFP) detection by using a localized surface plasmon coupled fluorescence (LSPCF) fiber-optic biosensor is setup and experimentally demonstrated. It is based on gold nanoparticle (GNP) and coupled with localized surface plasmon wave on the surface of GNP. In this experiment, the fluorophores are labeled on anti-AFP which are bound to protein A conjugated GNP. Thus, LSPCF is excited with high efficiency in the near field of localized surface plasmon wave. Therefore, not only the sensitivity of LSPCF biosensor is enhanced but also the specific selectivity of AFP is improved. Experimentally, the ability of real time measurement in the range of AFP concentration from 0.1ng/ml to 100ng/ml was detected. To compare with conventional methods such as enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA), the LSPCF fiber-optic biosensor performs higher or comparable detection sensitivity, respectively.

  8. Specific Genetic Immunotherapy Induced by Recombinant Vaccine Alpha-Fetoprotein-Heat Shock Protein 70 Complex

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoping; Lin, Huanping; Wang, Qiaoxia

    Purposes: To construct a recombinant vaccine alpha-fetoprotein (AFP)-heat shock protein (HSP70) complex, and study its ability to induce specific CTL response and its protective effect against AFP-producing tumor. Material/Methods: A recombinant vaccine was constructed by conjugating mouse alpha-fetoprotein to heat shock protein 70. By way of intracutaneous injection, mice were primed and boosted with recombinant vaccine mAFP/HSP70, whereas single mAFP or HSP70 injection as controls. The ELISPOT and ELISA were used to measure the frequency of cells producing the cytokine IFN-γ in splenocytes and the level of anti-AFP antibody of serum from immunized mice respectively. In vivo tumor challenge were carried out to assess the immune effect of the recombinant vaccine. Results: By recombinant mAFP/HSP70 vaccine immunization, the results of ELISPOT and ELISA showed that the number of splenic cells producing IFN-γ and the level of anti-AFP antibody of serum were significantly higher in mAFP/HSP70 group than those in mAFP and HSP70 groups (108.50±11.70 IFN-γ spots/106 cells vs 41.60±10.40 IFN-γ spots/106 cells, 7.32±3.14 IFN-γ spots/106 cells, P<0.01; 156.32±10.42 μg/mL vs 66.52±7.35 μg/mL, 5.73±2.89 μg/mL, P<0.01). The tumor volume in mAFP/HSP70 group was significantly smaller than that in mAFP and HSP70 groups (42.44±7.14 mm3 vs 392.23±12.46 mm3, 838.63±13.84 mm3, P<0.01). Conclusions: The study further confirmed the function of heat shock protein 70's immune adjuvant. Sequential immunization with recombinant mAFP/HSP70 vaccine could generate effective antitumor immunity on AFP-producing tumor. The recombined mAFP/HSP70 vaccine may be suitable for serving as an immunotherapy for hepatocellular carcinoma.

  9. Association between serum alpha-fetoprotein levels and fatty liver disease: A cross-sectional study

    PubMed Central

    Xu, Ping; Xu, Cheng-Fu; Wan, Xing-Yong; Yu, Chao-Hui; Shen, Chao; Chen, Peng; Xu, Gen-Yun; Li, You-Ming

    2014-01-01

    AIM: To investigate the association between serum alpha-fetoprotein (AFP) levels and fatty liver disease (FLD) in a Chinese population. METHODS: A cross-sectional study was performed among subjects who presented for a health examination at the First Affiliated Hospital, College of Medicine, Zhejiang University in 2013. FLD was diagnosed based on an ultrasonography examination. Serum AFP levels were measured with a chemiluminescence immunoassay. RESULTS: Of the 9800 subjects enrolled, 2601 were diagnosed with FLD. Subjects with FLD had higher serum AFP levels than those without the disease. Subjects with high serum AFP levels had a higher prevalence of FLD, metabolic syndrome, and its components. Univariate logistic analysis showed that elevated serum AFP levels were associated with an increased risk of FLD (OR = 1.057, 95%CI: 1.031-1.084). However, after adjusting for covariates, AFP no longer remained significantly associated with the risk factors for FLD. CONCLUSION: Our results suggest that serum AFP levels are significantly associated with FLD and that AFP acts as a cofactor, but not as an independent factor, for FLD. PMID:25206293

  10. Alpha fetoprotein DNA prime and adenovirus boost immunization of two hepatocellular cancer patients

    PubMed Central

    2014-01-01

    Background Alpha fetoprotein (AFP) is an oncofetal antigen over-expressed by many hepatocellular cancers (HCC). We previously demonstrated that HLA-A2-restricted epitopes derived from AFP are immunogenic in vitro and in vivo despite high circulating levels of this oncofetal antigen. In order to test a more broadly applicable, HLA-unrestricted, inexpensive, cell-free vaccine platform capable of activating tumor antigen-specific CD8+ and CD4+ T cells, we tested full length AFP in a plasmid DNA construct in combination with an AFP-expressing replication-deficient adenovirus (AdV) in a prime-boost vaccine strategy. Methods HCC patients who had an AFP+ tumor and previous treatment for HCC were screened and two patients received vaccination with three plasmid DNA injections followed by a single AdV injection, all delivered intramuscularly (i.m.). Results The vaccine was well tolerated and safe. Both patients showed immunologic evidence of immunization. The first patient had a weak AFP-specific T cell response, a strong AdV-specific cellular response and recurred with an AFP-expressing HCC at nine months. The second patient developed a strong AFP-specific CD8+ and CD4+ cellular response and an AdV neutralizing antibody response, and recurred at 18 months without an increase in serum AFP. Conclusions The AFP DNA prime-AdV boost vaccine was safe and immunogenic. Circulating anti-AdV neutralizing antibodies at baseline did not prohibit the development of AFP-specific cellular immunity. The patient who developed CD8+ and CD4+ AFP-specific T cell immunity had more favorable progression-free survival. The observations with these two patients support development of this vaccine strategy in a larger clinical trial. Trial registration ClinicalTrials.gov: NCT00093548 PMID:24708667

  11. Does alpha-fetoprotein contribute to the mortality and morbidity of human hepatocellular carcinoma? A commentary

    PubMed Central

    Mizejewski, Gerald J

    2016-01-01

    The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), while being the third leading cause of global cancer-related deaths. Although HCC incidence is less frequent in North America, it is a common malignancy in Asia and Africa associated with a high rate of mortality and morbidity due to ineffective therapies against cancer growth, invasion, and metastasis. It is well established that serum alpha-fetoprotein (AFP) is the “gold standard” biomarker for liver cancer; however, less known are the biological activities of AFP regarding carcinogenesis, growth, proliferation, and metastasis. Clinicians are well aware that increasing AFP serum levels parallel disease progression of HCC patients, but many are less knowledgeable in the lethal growth-promoting properties of AFP as an autocrine stimulator of hepatoma cell proliferation. This commentary addresses the mortality and morbidity concerning AFP in the genesis, growth, progression, and spread of HCC and emphasizes the perilous consequences of AFP-supported growth in human liver cancer even after liver resection and transplantation. Thus, AFP is not just a biomarker for HCC but also an ardent promoter of liver cancer growth and progression.

  12. Alpha-Fetoprotein levels in normal males from seven ethnic groups with different hepatocellular carcinoma risks.

    PubMed

    Sizaret, P; Tuyns, A; Martel, N; Jouvenceaux, A; Levin, A; Ong, Y W; Rive, J

    1975-08-22

    Alpha-Fetoprotein (AFP) levels of 1,335 males (15 years and older) of seven ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from Nairobi, forest, and the savanna region of the Ivory Coast) were determined by radioimmunoassay. A few elevated levels (up to 30 nanounits/ml) were detected in some normal individuals, especially in the older age-groups. In addition, there was a systematic age-dependency of AFP levels particularly evident in the groups from Singapore-Lyon, in which there was a 50% AFP increase between the ages of 20 and 40. Comparison between Africans on the one hand and people from Singapore-Lyon on the other hand revealed highly significant differences (p less than 0.001), especially in the younger groups, whereas Chinese, Malays, and Indians from Singapore had very similar AFP pattern; this suggests an important role for environmental factors in the regulation of AFP levels. The age dependency of the presumed effect of environmental factors is in keeping with experimental data showing that young animals respond more vigorously to AFP-stimulating factors. Although the incidence of hepatocellular carcinoma (HCC) differs in the three Singapore groups (the highest in Chinese and the lowest in Indians), no relationship was observed in this study between mean AFP level and HCC incidence in Singapore.

  13. Alpha fetoprotein antagonizes apoptosis induced by paclitaxel in hepatoma cells in vitro

    PubMed Central

    Zhu, Mingyue; Li, Wei; Lu, Yan; Dong, Xu; Chen, Yi; Lin, Bo; Xie, Xieju; Guo, Junli; Li, Mengsen

    2016-01-01

    Hepatocellular carcinoma (HCC) cell resistance to the effects of paclitaxel has not been adequately addressed. In this study, we found that paclitaxel significantly inhibited the viability of HLE, Bel 7402 and L-02 cells in a dose- and time-dependent manner. HLE cells and L-02 cells resisted the cytotoxicity of paclitaxel when transfected with pcDNA3.1-afp vectors. However, Bel 7402 cell sensitivity to paclitaxel was increased when transfected with alpha fetoprotein (AFP)-siRNA. Bel 7402 cell resistance to paclitaxel was associated with the expression of the “stemness” markers CD44 and CD133. Paclitaxel significantly inhibited growth and promoted apoptosis in HLE cells and L-02 cells by inducing fragmentation of caspase-3 and inhibiting the expression of Ras and Survivin, but pcDNA3.1-afp vectors prevented these effects. However, paclitaxel could not significantly promote the cleavage of caspase-3 or suppress the expression of Ras and Survivin in Bel 7402 cells. Silenced expression of AFP may be synergistic with paclitaxel to restrain proliferation and induce apoptosis, enhance cleavage of caspase-3, and suppress the expression of Ras and Survivin. Taken together, AFP may be an important molecule acting against paclitaxel-inhibited proliferation and induced apoptosis in HCC cells via repressing the activity of caspase-3 and stimulating the expression of Ras and Survivin. Targeted inhibition of AFP expression after treatment with paclitaxel is an available strategy for the therapy of patients with HCC. PMID:27255186

  14. Isolation and partial characterization of a specific alpha-fetoprotein receptor on human monocytes.

    PubMed Central

    Suzuki, Y; Zeng, C Q; Alpert, E

    1992-01-01

    Since a large body of data has suggested a significant role for alpha-fetoprotein (AFP) in the regulation of the immune response at a number of levels, we examined the possibility of a specific receptor for AFP on the immune recognition cell, the monocyte/macrophage. Microscopic autoradiography exhibited an obvious binding of AFP almost exclusively on human peripheral monocytes but not on lymphocytes. In a human monocyte cell line (U937) Scatchard plot analysis indicated the presence of two distinct AFP-specific binding sites with a Kd of 5 x 10(-11) M, 49 binding sites per cell, and 2.5 x 10(-7) M, 7,800 binding sites per cell. 125I-ASD-AFP, AFP-radiolabeled bifunctional photoactivatable thio-cleavable cross-linker, was used to isolate the AFP binding protein from U937 cells. After ultraviolet photoactivation, 125I-sulfosuccinimidyl 2-(p-azido-salicylamido)ethyl-1,3'-dithiopropionate was covalently linked to the putative receptor. Autoradiography of SDS gradient PAGE under reducing conditions showed a major radiolabeled band at between 62 and 65 kD. To confirm the specificity of the finding, recombination of AFP with the isolated receptor was examined in artificially reconstituted membrane vesicles, which also resulted in a single band at approximately 62-65 kD by SDS-PAGE autoradiography. From the data above, we concluded that human monocytes possess a specific AFP binding protein on the membrane, a putative receptor, which may be involved with the physiological regulation of the immune response. Images PMID:1383274

  15. Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma

    PubMed Central

    Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene’s expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment. PMID:27468205

  16. Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma.

    PubMed

    Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

    2016-07-21

    Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment. PMID:27468205

  17. The ontogeny of alpha-fetoprotein gene expression in the mouse gastrointestinal tract

    PubMed Central

    1990-01-01

    The ontogeny of alpha-fetoprotein (AFP) gene expression has been examined in the fetal and adult mouse gastrointestinal tract. AFP mRNA constitutes approximately 0.1% of total mRNA in the fetal gut. The transcripts were localized by in situ hybridization to the epithelial cells lining the villi of the fetal gut. At birth, AFP mRNA declines rapidly to achieve low adult basal levels, which are not affected by different alleles of raf, a gene that determines the adult basal level of AFP mRNA in the liver. The basal level in the adult gut is the consequence of continued AFP transcription in a small number of enteroendocrine cells that are distributed infrequently on the villi. These cells were identified by double antibody staining with antibodies to chromogranin A, an enteroendocrine cell marker and AFP. Previous studies resulted in the generation of a line of transgenic mice containing an internally deleted AFP gene that was greatly overexpressed in the fetal gut. The basis for the inappropriately high level expression of the transgene was shown to be the consequence of very high levels of transcription in the epithelial cells of the villi rather than to expression in inappropriate cell types. The cis-acting DNA sequences required for expression of the AFP gene in the gut were investigated using Caco-2 cells, a human colon adenocarcinoma cell line. These experiments indicated that, with one exception, the regulatory elements required in both the promoter and enhancer regions of the gene coincided with those that are necessary for high level expression in the liver. The one exception was enhancer II, located 5 kbp of DNA upstream of the gene, which exhibited no activity in Caco-2 cells. PMID:1691194

  18. Alpha-fetoprotein is a biomarker of unfolded protein response and altered proteostasis in hepatocellular carcinoma cells exposed to sorafenib.

    PubMed

    Houessinon, Aline; Gicquel, Albane; Bochereau, Flora; Louandre, Christophe; Nyga, Rémy; Godin, Corinne; Degonville, James; Fournier, Emma; Saidak, Zuzana; Drullion, Claire; Barbare, Jean-Claude; Chauffert, Bruno; François, Catherine; Pluquet, Olivier; Galmiche, Antoine

    2016-01-28

    Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC). A decrease in the serum levels of Alpha-fetoprotein (AFP) is reported to be the biological parameter that is best associated with disease control by sorafenib. In order to provide a biological rationale for the variations of AFP, we analyzed the various steps of AFP production in human HCC cell lines exposed to sorafenib. Sorafenib dramatically reduced the levels of AFP produced by HCC cells independently of its effect on cell viability. The mRNA levels of AFP decreased upon sorafenib treatment, while the AFP protein remained localized in the Golgi apparatus. Sorafenib activated the Regulated Inositol-Requiring Enzyme-1α (IRE-1α) and the PKR-like ER Kinase (PERK)-dependent arms of the Unfolded Protein Response (UPR). The inhibition of IRE-1α partially restored the mRNA levels of AFP upon treatment with sorafenib. The inhibition of both pathways partially prevented the drop in the production of AFP induced by sorafenib. The findings provide new insights on the regulation of AFP, and identify it as a biomarker suitable for the exploration of HCC cell proteostasis in the context of therapeutic targeting. PMID:26546044

  19. Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma.

    PubMed

    Charrière, Bérénice; Maulat, Charlotte; Suc, Bertrand; Muscari, Fabrice

    2016-07-28

    Alpha-fetoprotein (AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma (HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/mL could be an exclusion criterion, whereas values of < 15 ng/mL indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or "up-to-seven". We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed. PMID:27478538

  20. Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

    PubMed Central

    Charrière, Bérénice; Maulat, Charlotte; Suc, Bertrand; Muscari, Fabrice

    2016-01-01

    Alpha-fetoprotein (AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma (HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/mL could be an exclusion criterion, whereas values of < 15 ng/mL indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or “up-to-seven”. We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed. PMID:27478538

  1. Gold nanoparticles and polyethylene glycols functionalized conducting polyaniline nanowires for ultrasensitive and low fouling immunosensing of alpha-fetoprotein.

    PubMed

    Hui, Ni; Sun, Xiaotian; Song, Zhiling; Niu, Shuyan; Luo, Xiliang

    2016-12-15

    An ultrasensitive biosensor for alpha-fetoprotein was developed based on electrochemically synthesized polyaniline (PANI) nanowires, which were functionalized with gold nanoparticles (AuNPs) and polyethylene glycols (PEG). The prepared PEG/AuNPs/PANI composite, combining the electrical conductivity of the AuNPs/PANI with the robust antifouling ability of PEG, offered an ideal substrate for the development of low fouling electrochemical biosensors. Alpha-fetoprotein (AFP), a well-known hepatocellular carcinoma biomarker, was used as a model analyte, and its antibody was immobilized on the PEG/AuNPs/PANI for the construction of the AFP immunosensor. Using the redox current of PANI as the sensing signal, in addition to the good biocompatibility of PEG/AuNPs and the anti-biofouling property of PEG, the developed immunosensor showed improved biosensing performances, such as wide linear range and ultralow detection limit (0.007pgmL(-1)). More importantly, it is label-free, reagentless and low fouling, making it capable of assaying AFP in real serum samples without suffering from significant interference or biofouling.

  2. Binding of alpha-fetoprotein by immobilized monoclonal antibodies during episodes of zero-gravity obtained by parabolic flight

    NASA Technical Reports Server (NTRS)

    Spooner, Brian S.; Guikema, James A.; Barnes, Grady

    1990-01-01

    Alpha-fetoprotein (AFP), a single-chain polypeptide which is synthesized by the liver and yolk sac of the human fetus, provided a model ligand for assessing the effects of microgravity on ligand binding to surface-immobilized model receptor molecules. Monoclonal antibodies, used as receptors for AFP, were immobilized by covalent attachment to latex microparticles. Zero gravity environment was obtained by parabolic flight aboard NASA 930, a modified KC-135 aircraft. Buring the onset of an episode of zero gravity, ligand and receptor were mixed. Timed incubation (20 s) was terminated by centrifugation, the supernatant removed, and microparticies were assessed for bound AFP by immunochemical methods. The extent of binding was not influenced by microgravity, when compared with 1-G controls, which suggests that aberrant cellular activities observed in microgravity are not the simple expression of altered macromolecular interactions.

  3. Screening and Identifying a Novel ssDNA Aptamer against Alpha-fetoprotein Using CE-SELEX

    PubMed Central

    Dong, Lili; Tan, Qiwen; Ye, Wei; Liu, Dongli; Chen, Haifeng; Hu, Hongwei; Wen, Duo; Liu, Yang; Cao, Ya; Kang, Jingwu; Fan, Jia; Guo, Wei; Wu, Weizhong

    2015-01-01

    Alpha-fetoprotein (AFP) is a liver cancer associated protein and has long been utilized as a serum tumor biomarker of disease progression. AFP is usually detected in HCC patients by an antibody based system. Recently, however, aptamers generated from systematic evolution of ligands by exponential enrichment (SELEX) were reported to have an alternative potential in targeted imaging, diagnosis and therapy. In this study, AFP-bound ssDNA aptamers were screened and identified using capillary electrophoresis (CE) SELEX technology. After cloning, sequencing and motif analysis, we successfully confirmed an aptamer, named AP273, specifically targeting AFP. The aptamer could be used as a probe in AFP immunofluorescence imaging in HepG2, one AFP positive cancer cell line, but not in A549, an AFP negative cancer cell line. More interesting, the aptamer efficiently inhibited the migration and invasion of HCC cells after in vivo transfection. Motif analysis revealed that AP273 had several stable secondary motifs in its structure. Our results indicate that CE-SELEX technology is an efficient method to screen specific protein-bound ssDNA, and AP273 could be used as an agent in AFP-based staining, diagnosis and therapy, although more works are still needed. PMID:26497223

  4. Autosomal recessive spinocerebellar ataxia and peripheral neuropathy with raised alpha-fetoprotein.

    PubMed

    Izatt, Louise; Németh, Andrea H; Meesaq, Anjela; Mills, Kerry R; Taylor, A Malcolm R; Shaw, Christopher E

    2004-07-01

    We describe three patients from two families with progressive spinocerebellar ataxia, peripheral neuropathy, raised alpha-fetoprotein (AFP) and hypercholesterolaemia. Two siblings had identical clinical features, with late childhood onset of symptoms and slow progression, requiring crutches to walk at ages 37 and 38 years. Another patient developed ataxia aged 13 years and became wheel-chair bound by 20 years of age. Although they all had raised serum AFP levels, their clinical, immunological, biochemical, cytogenetic and molecular genetic studies failed to support a diagnosis of Ataxia Telangiectasia. Extensive investigation including imaging, biochemical and genetic studies excluded other known ataxias. Their clinical features most closely resemble the phenotype of a single consanguineous Japanese family with four individuals affected by spinocerebellar ataxia, peripheral neuropathy, raised AFP and hypercholesterolaemia. Homozygosity mapping has identified a locus in this Japanese family at 9q34. Haplotype analysis of our cases demonstrated possible linkage to 9q34, suggesting these may be the first Caucasian families described with this disorder.

  5. Sensitive amperometric immunosensor for alpha-fetoprotein based on carbon nanotube/gold nanoparticle doped chitosan film.

    PubMed

    Lin, Jiehua; He, Chunyan; Zhang, Lijuan; Zhang, Shusheng

    2009-01-01

    A novel strategy for the fabrication of sensitive immunosensor to detect alpha-fetoprotein (AFP) in human serum has been proposed. The immunosensor was prepared by immobilizing AFP antigen onto the glassy carbon electrode (GC) modified by gold nanoparticles and carbon nanotubes doped chitosan (GNP/CNT/Ch) film. GNP/CNT hybrids were produced by one-step synthesis based on the direct redox reaction. The electrochemical properties of GNP/CNT/Ch films were characterized by impedance spectroscopy and cyclic voltammetry. It was indicated that GNP/CNT nanohybrid acted as an electron promoter and accelerated the electron transfer. Sample AFP, immobilized AFP, and alkaline phosphatase (ALP)-labeled antibody were incubated together for the determination based on a competitive immunoassay format. After the immunoassay reaction, the bound ALP label on the modified GC led to an amperometric response of 1-naphthyl phosphate (1-NP), which was changed with the different antigen concentrations in solution. Under the optimized experimental conditions, the resulting immunosensor could detect AFP in a linear range from 1 to 55 ng ml(-1) with a detection limit of 0.6 ng ml(-1). The proposed immunosensor, by using GNP/CNT/Ch as the immobilization matrix of AFP, offers an excellent amperometric response of ALP-anti-AFP to 1-NP. The immunosensor provided a new alternative to the application of other antigens or other bioactive molecules. PMID:18848914

  6. Highly sensitive, label-free and real-time detection of alpha-fetoprotein using a silicon nanowire biosensor.

    PubMed

    Zhou, Fan; Li, Zengyao; Bao, Zengtao; Feng, Kang; Zhang, Ye; Wang, Tong

    2015-11-01

    Alpha-fetoprotein (AFP) is a tumor-associated fetal protein that can be expressed in large amounts in adult tumor cells, serving as a useful clinical tumor-marker. Silicon nanowire (SiNW) biosensors have emerged as a powerful tool in detecting protein biomarkers, due to their ultrahigh sensitivity, real-time response and label-free detection. We fabricated a SiNW-based field-effect transistor (FET) according to "top-down" methodology. First, anti-AFP antibodies were immobilized onto the surface of the SiNW-FET. A polydimethylsiloxane (PDMS) microchannel was then integrated to the modified SiNW-FET. Various concentrations of AFP were then pumped through the sensing area. We observed a current change that corresponded to binding of AFP onto the surface of our anti-AFP functionalized SiNW-FET biosensor. Concentrations of AFP as low as 0.1 ng/mL were detected. The results implicate our SiNW biosensor as an effective AFP biomarker detector with promising potential in clinical applications. PMID:26205419

  7. Fluorescence Quenching of Alpha-Fetoprotein by Gold Nanoparticles: Effect of Dielectric Shell on Non-Radiative Decay

    NASA Astrophysics Data System (ADS)

    Zhu, Jian; Li, Jian-Jun; Wang, A.-Qing; Chen, Yu; Zhao, Jun-Wu

    2010-09-01

    Fluorescence quenching spectrometry was applied to study the interactions between gold colloidal nanoparticles and alpha-fetoprotein (AFP). Experimental results show that the gold nanoparticles can quench the fluorescence emission of adsorbed AFP effectively. Furthermore, the intensity of fluorescence emission peak decreases monotonously with the increasing gold nanoparticles content. A mechanism based on surface plasmon resonance-induced non-radiative decay was investigated to illuminate the effect of a dielectric shell on the fluorescence quenching ability of gold nanoparticles. The calculation results show that the increasing dielectric shell thickness may improve the monochromaticity of fluorescence quenching. However, high energy transfer efficiency can be obtained within a wide wavelength band by coating a thinner dielectric shell.

  8. Fluorescence Quenching of Alpha-Fetoprotein by Gold Nanoparticles: Effect of Dielectric Shell on Non-Radiative Decay.

    PubMed

    Zhu, Jian; Li, Jian-Jun; Wang, A-Qing; Chen, Yu; Zhao, Jun-Wu

    2010-06-15

    Fluorescence quenching spectrometry was applied to study the interactions between gold colloidal nanoparticles and alpha-fetoprotein (AFP). Experimental results show that the gold nanoparticles can quench the fluorescence emission of adsorbed AFP effectively. Furthermore, the intensity of fluorescence emission peak decreases monotonously with the increasing gold nanoparticles content. A mechanism based on surface plasmon resonance-induced non-radiative decay was investigated to illuminate the effect of a dielectric shell on the fluorescence quenching ability of gold nanoparticles. The calculation results show that the increasing dielectric shell thickness may improve the monochromaticity of fluorescence quenching. However, high energy transfer efficiency can be obtained within a wide wavelength band by coating a thinner dielectric shell.

  9. Maternal serum alpha fetoprotein in monozygotic and dizygotic twin pregnancies.

    PubMed

    Thom, H; Buckland, C M; Campbell, A G; Thompson, B; Farr, V

    1984-01-01

    Maternal serum alpha-fetoprotein (MSAFP) values in the second trimester have been related to pregnancy outcome for 100 normal twin pairs, 42 monozygous (MZ) and 58 dizygous (DZ), liveborn after 28 weeks gestation. The median MSAFP value was 1.9 multiples of the median value (MOM) for uncomplicated singleton pregnancies. Both very low and very high MSAFP values were associated with twins of low birthweight. MSAFP values were higher in MZ than DZ twin pregnancies particularly those with dizygotes of like-sex. This effect was even more marked when only dichorionic like-sex twin pairs were compared. PMID:6209699

  10. Diagnostic Value of the Combination of Golgi Protein 73 and Alpha-Fetoprotein in Hepatocellular Carcinoma: A Meta-Analysis

    PubMed Central

    Liu, Xuexiang; Peng, Zheng; Meng, Jie; Dai, Shengming

    2015-01-01

    Conflicting results have been widely reported on the use of Golgi protein 73 (GP73) as a serum biomarker for diagnosing hepatocellular carcinoma (HCC). This study evaluated the accuracy of GP73, alpha-fetoprotein (AFP), and GP73 + AFP for diagnosing HCC. The meta-analysis was performed on 11 studies that were selected by means of a comprehensive systematic literature review. Summary diagnostic accuracy, meta-regression analysis for heterogeneity and publication bias, and other statistical analyses were performed using Meta-Disc (version 1.4) and Stata (version 12.0). Pooled sensitivity, specificity, and diagnostic odds ratio were 0.77 (95% CI: 0.75–0.79), 0.91 (95% CI: 0.90–0.92), and 12.49 (95% CI: 4.91–31.79) for GP73; 0.62 (95% CI: 0.60–0.64), 0.84 (95% CI: 0.83–0.85), and 11.61 (95% CI: 8.02–16.81) for AFP; and 0.87 (95% CI: 0.85–0.89), 0.85 (95% CI: 0.84–0.86), and 30.63 (95% CI: 18.10–51.84) for GP73 + AFP. The area under the curve values were 0.86, 0.84, and 0.91 for GP73, AFP, and GP73 + AFP, respectively. These results indicate that for HCC diagnosis, the accuracy of GP73 was higher than that of AFP, and that GP73 + AFP exhibited significantly higher diagnostic accuracy than did GP73 or AFP alone. PMID:26441340

  11. Distribution of [sup 65]Zn labeled alpha-fetoprotein during proliferation of the BW7756 murine hepatoma

    SciTech Connect

    Keenan, J.F.

    1990-01-01

    The radiolabeling of alpha-fetoprotein (AFP) with [sup 65]Zn for the determination of its biodistribution was studied in mice bearing the BW7756 murine hepatoma as compared to that found with normal mice. AFP is an oncofetal protein of about 70,000 daltons associated with pregnancy and certain cancers (e.g., hepatoma). The AFP was purified from mouse amniotic fluid (MAF) using polyacrylamide gel electrophoresis (PAGE) and higher performance liquid chromatography (HPLC). The biological activity of AFP was maintained through the separation procedures and the purity was determined using double immunodiffusion (DID), immunoelectrophoresis (IEP) and sodium dodecyl sulfate electrophoresis (SDS). The labeling procedures included removal of intrinsic metal with EDTA, incubation with radiotracer ([sup 65]Zn) and buffer, followed by removal of unbound [sup 65]Zn using gel filtration chromatography. The results correlated well with Zn fluctuations recorded by other techniques (RIXRF, radiotracer [sup 65]Zn). Large amounts of [sup 65]Zn-AFP were localized in the liver, spleen and tumor with significant elevations above normal in the log growth phase (day 14-18). [sup 65]Zn-AFP levels in the skin, pancreas, brain and thyroid decreased as the tumor mass increased. Tumor [sup 65]Zn-AFP uptake increased with time but leveled off in the late log phase (day 21) due to tumor necrosis. In light of the results of this investigation, and previous work stating that AFP binds Zn with a higher affinity than does albumin, it is suggestive that the Zn fluctuations observed in the earlier hepatoma studies were due to the in vivo binding of Zn to AFP. These results confirm the thesis that intrinsic labeling (replacement of naturally bound ligands with radioactive analogs) does not alter the biochemical integrity as non-intrinsic labeling (e.g., Iodine) may.

  12. A Novel Sandwich Electrochemical Immunosensor Based on the DNA-Derived Magnetic Nanochain Probes for Alpha-Fetoprotein

    PubMed Central

    Gan, Ning; Jia, Liyong; Zheng, Lei

    2011-01-01

    One novel electrochemical immunosensor was constructed by immobilizing capture antibody of alpha-fetoprotein (AFP Ab1) on a nafion/nanogold-particle modified glassy carbon electrode. With a sandwich immunoassay, one DNA-derived magnetic nanoprobe, simplified as DNA/(ZMPs—HRP-AFP Ab2)n, was employed for the detection of AFP. The fabricated procedure of the proposed biosensor was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. The performance and factors influencing the performance of the biosensor were also evaluated. Under optimal conditions, the developed biosensor exhibited a well-defined electrochemical behavior toward the reduction of AFP ranging from 0.01 to 200 ng/mL with a detection limit of 4 pg/mL (S/N = 3). The biosensor was applied to the determination of AFP in serum with satisfactory results. It is important to note that the sandwich nanochainmodified electro-immunosensor provided an alternative substrate for the immobilization of other tumor markers. PMID:22013390

  13. Hepatitis B Virus X Protein Driven Alpha Fetoprotein Expression to Promote Malignant Behaviors of Normal Liver Cells and Hepatoma Cells

    PubMed Central

    Zhu, Mingyue; Lu, Yan; Li, Wei; Guo, Junli; Dong, Xu; Lin, Bo; Chen, Yi; Xie, Xieju; Li, Mengsen

    2016-01-01

    Background: The infection of Hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma(HCC), HBV-X protein(HBx) is able to induce expression of alpha-fetoprotein(AFP) in normal liver cells, and AFP harbors a function to promote malignant transformation of normal liver cells, but the role AFP playing in malignant behaviors of HCC cells is still unclear. Methods: Fifty-six liver tissue samples were collected from the clinical patients through hepatectomy(include normal liver tissues, HBV-related hepatitis liver tissues and HBV-related HCC tissues), and diagnosis of these tissues by pathology section, expression of AFP, Ras and CXCR4 were evidenced by immunohisochemical staining and Western blotting; The proliferation of human normal liver cells line L-02 cells and human hepatoma cells line, HLE cells(non AFP-producing) were performed by MTT method; Repaired capacity of L-02 and HLE cells were compared by wound healing assay; Migration and invasion of these cells were analyzed by Transwell chamber assay; HBx expressed vectors(pcDNA3.1-HBx) were constructed and transfected into L-02 and HLE cells, effects of pcDNA3.1-HBx on the malignant behaviors were also detected by MTT, Transwell chamber assay and the expression of AFP, Ras and CXCR4 were evidenced by Western blotting. Results: we found that expression of AFP, Ras and CXCR4 in HBV-related HCC and lymph nodes metastasis tissues were significantly elevated compared with HBV-related HCC, non metastasis tissues and HBV-related hepatitis tissues; Expression of AFP, Ras and CXCR4 in HBV-related hepatitis tissues were significantly enhanced compared with normal liver tissues; The growth ratio, migratory and invasive ability, expression of AFP, Ras and CXCR4 of the cells were outstanding promoted while L-02 and HLE cells were transfected with pcDNA3.1-HBx vectors. The proliferation ratio, migration and invasion ability, and expression of Ras and CXCR4 were significantly inhibited while

  14. A highly sensitive biosensor for tumor maker alpha fetoprotein based on poly(ethylene glycol) doped conducting polymer PEDOT.

    PubMed

    Cui, Min; Song, Zhiling; Wu, Yumin; Guo, Bing; Fan, Xiaojian; Luo, Xiliang

    2016-05-15

    Biocompatible polymers, such as poly(ethylene glycol) (PEG), are of great significance in the development of bio-interfaces and biosensors, as they possess excellent biocompatibility and are easy for modification. A novel highly biocompatible polymer composite was synthesized herein through electrochemical polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and a PEG derivative, 4-arm PEG terminated with thiol groups. The electrodeposited conducting polymer composite of PEG doped PEDOT (PEDOT/PEG) exhibited flake-like nanostructure, large surface area and outstanding stability. In order to further immobilize antibodies, gold nanoparticles (AuNPs) were introduced to the PEDOT/PEG composite surface through their unique interaction with the thiol groups. AuNPs modified PEDOT/PEG provided a desirable support for the immobilization of various biomolecules such as antibodies for alpha fetoprotein (AFP), a vital tumor biomarker for liver cancer. The fabricated AFP biosensor demonstrated favorable selectivity, high sensitivity, and ultralow detection limit. Furthermore, owing to the presence of PEG polymers that are highly hydrophilic, such AuNPs/PEDOT/PEG based AFP biosensor also exhibited good anti-fouling ability, and it was capable of assaying target AFP in 10% (V/V) human serum samples, indicating highly feasible potential for clinical diagnosis.

  15. Selection tool alpha-fetoprotein for patients waiting for liver transplantation: How to easily manage a fractal algorithm

    PubMed Central

    Lai, Quirino; Levi Sandri, Giovanni Battista; Lerut, Jan

    2015-01-01

    Alpha-fetoprotein (AFP) behavior in patients with hepatocellular carcinoma (HCC) waiting for liver transplant (LT) represents a perfect biological example of a fractal model in which its progressive modification and possible future prediction of its values are very hard to capture. As a consequence, AFP represents a useful but poorly manageable tool to increase the ability to better select HCC patients waiting for LT. Trying to find a “fil-rouge” in the recent literature, no definitive answers can be done to several open questions: (1) the best AFP value to adopt; (2) the best cut-off measurement; and (3) the best way to comfortably capture the effective, time-related, fluctuations of this biological marker. More, structured and prospective, studies using serial determination of AFP values within and without the context of locoregional therapies are needed in order to find the “ideal” (static and dynamic) cut-off values allowing to respond to all the still open questions in this field of transplant oncology. PMID:26244064

  16. Label-free alpha fetoprotein immunosensor established by the facile synthesis of a palladium-graphene nanocomposite.

    PubMed

    Qi, TingTing; Liao, JinFeng; Li, YiSong; Peng, JinRong; Li, WenTing; Chu, BingYang; Li, He; Wei, YuQuan; Qian, ZhiYong

    2014-11-15

    In this study, we established a sensitive label-free immunosensor by palladium-reduced graphene oxide (Pd-rGO), which was prepared by one-pot synthesis under the reduction of extra-injected CO gas. The Pd-rGO nanocomposite structure has been confirmed by TEM, SEM, X-ray diffraction, and UV-vis spectroscopy. The Pd-rGO nanocomposite exhibited excellent stability in aqueous dispersion. The Pd-rGO-based label-free electrochemical immunosensor was used for detection of the hepatocellular carcinoma (HCC) biomarker alpha fetoprotein (AFP). The immunosensor determination was based on the fact that due to the formation of antigen-antibody immunocomplex, the decreased response amperometric currents of H2O2 were directly proportional to the concentrations of AFP. The limit of detection of this immunosensor for AFP detection is 5 pg/mL, and is linear from 0.01 to 12 ng/mL. The proposed immunosensor has been used to determine AFP in clinical serum samples with satisfactory results. This suggests the sensor may have great potential utility in the clinic. PMID:24906081

  17. AFP-L3 — EDRN Public Portal

    Cancer.gov

    AFP-L3, also known as lectin-bound AFP, is an isoform of AFP, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatoma or teratoma. The L3 isoform is specific to malignant tumors and its detected presence may serve to identify patients who could benefit from monitoring for the development of HCC in high risk populations (i.e. chronic hepatitis, liver cirrhosis).

  18. c-Ha-ras down regulates the alpha-fetoprotein gene but not the albumin gene in human hepatoma cells.

    PubMed Central

    Nakao, K; Lawless, D; Ohe, Y; Miyao, Y; Nakabayashi, H; Kamiya, H; Miura, K; Ohtsuka, E; Tamaoki, T

    1990-01-01

    We studied the effects of transfection of the normal c-Ha-ras gene, rasGly-12, and its oncogenic mutant, rasVal-12, on expression of the alpha-fetoprotein (AFP) and albumin genes in a human hepatoma cell line, HuH-7. The mutant and, to a lesser extent, the normal ras gene caused reduction of the AFP mRNA but not the albumin mRNA level in transfected HuH-7 cells. Cotransfection experiments with a rasVal-12 expression plasmid and a chloramphenicol acetyltransferase reporter gene fused to AFP regulatory sequences showed that rasVal-12 suppressed the activity of enhancer and promoter regions containing A + T-rich sequences (AT motif). In contrast, rasVal-12 did not affect the promoter activity of the albumin and human hepatitis B virus pre-S1 genes even though these promoters contain homologous A + T-rich elements. ras transfection appeared to induce phosphorylation of nuclear proteins that interact with the AFP AT motif, since gel mobility analysis revealed the formation of slow-moving complexes which was reversed by phosphatase treatment. However, similar changes in complex formation were observed with the albumin and hepatitis B surface antigen pre-S1 promoters. Therefore, this effect alone cannot explain the specific down regulation of the AFP promoter and enhancer activity. ras-mediated suppression of the AFP gene may reflect the process of developmental gene regulation in which AFP gene transcription is controlled by a G-protein-linked signal transduction cascade triggered by external growth stimuli. Images PMID:1690841

  19. Maternal serum screening for aneuploid pregnancy by alpha-fetoprotein, hCG, and unconjugated estriol.

    PubMed

    Heyl, P S; Miller, W; Canick, J A

    1990-12-01

    A number of serum screening protocols are either currently in use or proposed to identify pregnant women under 35 years of age who are at increased risk for a Down syndrome fetus. It has been suggested that these same screening methods be applied to gravidas over 35 years of age to identify those women who should be offered amniocentesis. To evaluate the efficacy of screening for detection of aneuploid pregnancy in this age group, the serum samples of 34 women who underwent amniocentesis and who had confirmed fetal aneuploidy were assayed for alpha-fetoprotein (AFP), hCG, and unconjugated estriol (E3). These concentrations were compared with those of 85 women with known euploid pregnancy who underwent amniocentesis for advanced maternal age. The mean multiple of the median (MoM) for each of the three markers was significantly different from control values in cases of trisomy 21 (AFP median MoM = 0.82; unconjugated E3 median MoM = 0.77; and hCG median MoM = 1.89). These differences were not found when other aneuploidies were considered. Likelihood ratios were calculated for cases and controls and examined for their ability to predict the need for amniocentesis, based on currently recommended risk levels. There was a significant difference between the mean likelihood ratio for cases of trisomy 21 compared with that of controls (mean likelihood ratio = 13.48); there was no significant difference for other aneuploidies (mean likelihood ratio = 1.08). Of the 16 cases of trisomy 21 analyzed, four would not have been diagnosed antenatally if recommendation against amniocentesis had been made based on each woman's individual age-specific risk as modified by her likelihood ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1700348

  20. Human hepatocyte growth factor in alcoholic liver disease: a comparison with change in alpha-fetoprotein. Department of Veterans Affairs Cooperative Study Group 275.

    PubMed

    Mendenhall, C L; Roos, F; Moritz, T E; Roselle, G A; Chedid, A; Grossman, C J; Rouster, S D; Bennett, G L; Lake, J R

    1996-12-01

    To evaluate the hepatic regenerative response in patients with alcoholic liver disease, sera from 263 patients with severe alcoholic hepatitis and/or cirrhosis were analyzed for hepatocyte growth factor (HGF) and alpha-fetoprotein (AFP). HGF concentration was elevated above healthy controls in 95% of the patients (median level = 2.4 ng/ml), whereas AFP tended to be depressed below controls (median level = 4.1 ng/ml). Correlations with parameters of liver injury (i.e., ascites, encephalopathy, AST bilirubin, and protime) all showed a more significant correlation with HGF concentrations than those of AFP. Patients with HGF levels below the mean (4 ng/ml) exhibited significantly better survival (median survival = 35 months vs. 8.5 months for those with HGF > or = 4 ng/ml; p = 0.007). Serum HGF levels were associated with various specific histologic features of alcoholic hepatitis that included, but were not exclusively related to, necrosis. PMID:8986214

  1. Distribution of albumin and alpha-fetoprotein mRNAs in normal, hyperplastic, and preneoplastic rat liver.

    PubMed Central

    Alpini, G.; Aragona, E.; Dabeva, M.; Salvi, R.; Shafritz, D. A.; Tavoloni, N.

    1992-01-01

    The nature of bile duct-like (oval) cells proliferating during chemical hepatocarcinogenesis has been controversial. To investigate this issue further, the authors compared the hepatic distribution of albumin (ALB) and alpha-fetoprotein (AFP) mRNAs in rats in which oval cell proliferation was induced by feeding a choline-devoid diet containing 0.1% ethionine (CDE, a hepatocarcinogenic diet) with that in normal rats and in rats in which biliary epithelial cell hyperplasia was induced by either bile duct ligation or feeding alpha-naphthylisothiocyanate (ANIT). Northern blot analysis in parenchymal and nonparenchymal liver cells isolated from these animals demonstrated that ALB mRNA was present in the hepatocytes of both control and experimental animals, whereas this transcript was detected in nonparenchymal epithelial cells only in CDE-fed rats. Alpha-fetoprotein mRNA was not seen in either parenchymal or nonparenchymal cells isolated from normal or hyperplastic livers induced by bile duct ligation or ANIT feeding. In CDE-fed rats, however, both parenchymal and nonparenchymal cell populations displayed AFP message. In situ hybridization directly demonstrated nonparenchymal cell expression of both ALB and AFP transcripts in CDE-fed rats. Most surprisingly, ALB and AFP mRNAs were also detected by in situ hybridization in occasional nonparenchymal cells located in portal tracts near the limiting plate in normal liver, as well as under conditions associated with bile duct hyperplasia. Immunohistochemical studies of intermediate filament proteins, cytokeratin 19 (a marker of glandular epithelia), vimentin (a marker of mesenchymal lineage), and desmin (a marker of muscle cell differentiation) demonstrated that oval cells, as well as normal and hyperplastic bile duct cells, were positive for cytokeratin 19 and negative for both vimentin and desmin. Cytokeratin-positive oval cells formed duct profiles and were connected to preexisting ductules and ducts. These results are

  2. Alpha-fetoprotein production by a malignant mixed müllerian tumour of the uterus.

    PubMed Central

    Phillips, K A; Scurry, J P; Toner, G

    1996-01-01

    A case of alpha-fetoprotein production by a uterine malignant mixed müllerian tumour is described. The patient was a 68 year old woman who developed intraabdominal recurrence of a stage 1 uterine tumour which had been treated surgically seven years previously. Her serum alpha-fetoprotein was raised at 21,000 micrograms/l (normal < 10 micrograms/l) and staining with immunoperoxidase confirmed that the tumour was the site of alpha-fetoprotein production. The patient was treated with combination chemotherapy but died two weeks after the first course. This is believed to be only the second such case reported. Images PMID:8655717

  3. Characterization of Alpha-fetoprotein Levels in Three Dolphin Species: Development of Sensitive Immunoassays for Analysis of the Pregnancy-associated Variations

    PubMed Central

    MORITA, Yuka; HIRAMATSU, Naoshi; FUJITA, Toshiaki; AMANO, Haruna; KATSUMATA, Etsuko; ARAI, Kazutoshi; IWASAKI, Toshihide; TODO, Takashi; HARA, Akihiko

    2013-01-01

    Abstract A single radial immunodiffusion (SRID) assay and a chemiluminescent immunoassay (CLIA) were initially developed for alpha-fetoprotein (AFP) of the striped dolphin. Utilizing these developed assays, we investigated pregnancy-associated changes in the levels of AFP in the sera of fetuses and pregnant females of three dolphin species; samples were either collected from captive individuals or obtained as fishery by-products. The concentrations of AFP in the fetal serum ranged from 419.0 to 2026.3 μg/ml in the striped dolphin, 12.6 to 1218.7 μg/ml (for an AFP equivalent; eqAFP) in the common bottlenose dolphin and 770.6 to 3129.1 μg eqAFP/ml in the Risso's dolphin. AFP levels decreased with increased fetal size in fetuses over 20 cm in length. The concentrations of AFP in sera of pregnant females ranged from 7.18 to 8068.7 ng/ml in the striped dolphin, 6.6 to 1241.1 ng eqAFP/ml in the common bottlenose dolphin and 3.4 to 2868.7 ng eqAFP/ml in the Risso's dolphin. The levels in most pregnant females were equal to or lower than those found in males and nonpregnant individuals, although a few pregnant females exhibited extremely high levels (in the range of hundreds to thousands of nanograms per milliliter). Such high levels of AFP were not observed during pseudopregnancy. To our knowledge, this is the first report on basal profiles for serum AFP levels in small odontocetes. The profiles indicated that AFP may play a significant role during embryonic development, although maternal levels do not appear to be a diagnostic biomarker for monitoring pregnancy. PMID:23656975

  4. Female mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.

    PubMed

    Brock, Olivier; Keller, Matthieu; Douhard, Quentin; Bakker, Julie

    2012-01-01

    The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT) and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus) as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus), as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

  5. Des-gamma carboxy prothrombin (PIVKA-II) and alpha-fetoprotein producing gastric cancer with multiple liver metastases.

    PubMed

    Takahashi, Yoshihisa; Inoue, Tohru

    2003-04-01

    We describe the case of an 87-year-old woman who presented to Tokyo Kousei Nenkin Hospital because of appetite loss and general fatigue. Multiple liver masses and Borrmann type 2 gastric tumor were detected. A clinical diagnosis of hepatocellular carcinoma and gastric cancer was made based on the patient's high levels of serum alpha-fetoprotein (AFP; 490 200 ng/mL) and protein induced by vitamin K absence or antagonist-II (PIVKA-II, 2284 mAU/mL). The patient's general condition worsened gradually and she died 42 days after admission. Autopsy revealed that the predominant histological structure of the gastric tumor was trabecular or sheet-like, although a tubular structure was also found. Venous invasion was prominent. Immunohistochemically, the tumor tissue was positive for AFP and a few tumor cells were positive for PIVKA-II. The histological appearance and immunohistochemical features of the hepatic tumors resembled that of the gastric tumor. This case was pathologically diagnosed as AFP- and PIVKA-II-producing gastric carcinoma with multiple liver metastases. When tumors are found in the stomach and liver and serum PIVKA-II level is abnormally high, the possibility of PIVKA-II-producing gastric cancer with liver metastasis should be considered, especially when hepatitis virus markers are negative and liver cirrhosis is not present.

  6. Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

    PubMed Central

    Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

    2015-01-01

    Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy. PMID:26640716

  7. Congenital nephrosis: detection of index cases through maternal serum alpha-fetoprotein screening.

    PubMed

    Hogge, W A; Hogge, J S; Schnatterly, P T; Sun, C J; Blitzer, M G

    1992-11-01

    Congenital nephrosis is an autosomal recessive disorder with an incidence of 1 in 8000 in Finland, but it is quite rare in non-Finnish populations. In families known to be at risk, prenatal detection is possible by means of maternal serum and/or amniotic fluid alpha-fetoprotein levels. We report the antenatal diagnosis of four cases of congenital nephrosis, three of which were index cases, through maternal serum alpha-fetoprotein screening. The diagnosis was confirmed at birth in two infants. Two patients elected to terminate their pregnancies, and the diagnoses were confirmed pathologically (obliteration of foot processes on electron microscopy of fetal glomeruli) in both. In cases of elevated maternal serum alpha-fetoprotein, with unexplained and marked elevations of amniotic fluid alpha-fetoprotein and normal acetylcholinesterase levels, the diagnosis of congenital nephrosis must be considered regardless of ethnic origin.

  8. Maternal alpha-fetoprotein screening: two years' experience in a low-risk district.

    PubMed

    Standing, S J; Brindle, M J; Macdonald, A P; Lacey, R W

    1981-09-12

    Over a two-year period, 3479 pregnant women in the Kings' Lynn Health District were screened for neural tube defects by estimation of maternal serum alpha-fetoprotein. Most pregnancies were scanned by sonar for fetal maturity. Eight women had fetuses with open neural tube defects; four with anencephaly were associated with very high alpha-fetoprotein values. Of the four with open neural tube defects without anencephaly, only one was detected by screening and confirmed after amniocentesis. One other had a raised serum alpha-fetoprotein but a normal amniotic fluid value. The other two affected fetuses were missed. This disappointing outcome was attributed to the poor predictive value of alpha-fetoprotein in detecting open neural tube defects (anencephaly apart) rather than to errors in its estimation or in assessment of fetal maturity by sonar scan. We question the validity of screening, particularly in areas of intermediate or low incidence.

  9. Abnormal maternal serum alpha fetoprotein and pregnancy outcome.

    PubMed

    Zarzour, S J; Gabert, H A; Diket, A L; St Amant, M; Miller, J M

    1998-01-01

    The objective was to assess the occurrence of miscarriages, low birth weight, and karyotype abnormalities found with low and elevated maternal serum alpha-fetoprotein (MSAFP) among women who had genetic amniocentesis performed. A retrospective study of 2,159 women who had MSAFP analysis prior to amniocentesis was conducted. Pregnancy outcomes were obtained from record review and physicians follow-up. Limits of MSAFP used in analysis were <0.5 adjusted multiples of the median (MOM) (lower levels) and >2.0 MOM (upper levels). Autosomal trisomy was found in 1.6% with low, 0.9% normal, and 0.6% with elevated MSAFP values. Sex chromosome abnormalities were present only in patients with normal MSAFP, [45X (n = 6), 47XXY (n = 2), 69XXX]. Of five open neural tube defects, four had elevated MSAFP and one had a normal value. Omphalocele was identified in four patients, two with normal and two with elevated MSAFP. Gastroschisis was found in one low and one elevated MSAFP. Amniotic fluid alpha-fetoprotein (AFAFP) values did not correlate with MSAFP values. Patients with low MSAFP levels had a greater prevalence of abnormal karyotype (19 of 249, prevalence = 0.076) than patients with an elevated MSAFP level (2 or 166, prevalence = 0.012 OR (odds ratio) = 0.20 (P value = 0.024) when unadjusted for maternal age, and OR = 0.09 (P value = 0.001) when adjusted for maternal age. Spontaneous abortion occurred more often in patients with elevated (4 of 166, or 4%) than normal or low (20 of 1948, or 1%) values of MSAFP (odds ratio 4.32, P = 0.020 when adjusted for maternal age). Birth weight below 2,500 g was present less frequently with low or normal MSAFP (136 of 1,760, or 7.7%) than in elevated MSAFP (21 of 144 or 14.6%) (odds ratio 2.04, P = 0.005, unadjusted; and odds ratio = 2.32, P = 0.003, adjusted for maternal age). Female fetuses were present more often with low MSAFP (136 of 249, or 55%) than elevated levels 43% (71 of 164, or 43%; P = 0.024). We conclude that patients

  10. Synthesis of CdTe/CdS/ZnS quantum dots and their application in imaging of hepatocellular carcinoma cells and immunoassay for alpha fetoprotein

    NASA Astrophysics Data System (ADS)

    Tian, Jianniao; Liu, Rongjun; Zhao, Yanchun; Peng, Yan; Hong, Xue; Xu, Qing; Zhao, Shulin

    2010-07-01

    We report the imaging of hepatocellular carcinoma cells and the immunoassay for alpha fetoprotein (AFP) using CdTe/CdS/ZnS core-shell-shell QDs. Stable and high PLQY (20%-48%) CdTe/CdS/ZnS core-shell-shell QDs were synthesized by a stepwise process. Bioconjugation of the core-shell-shell QDs with streptavidin (SA) was successfully applied in immunofluorescent imaging of the human hepatocellular carcinoma (HCC) cell line HepG2.2.15. Furthermore, the thioglycolic acid (TGA)-capped CdTe/CdS/ZnS core-shell-shell QDs fluorescence lifetime is longer than fluorescein, so it was first engaged to conjugate with antigen for the determination of protein (AFP) by fluorescence polarization immunoassay.

  11. A cyclic peptide derived from alpha-fetoprotein inhibits the proliferative effects of the epidermal growth factor and estradiol in MCF7 cells.

    PubMed

    Torres, Cristian; Antileo, Elmer; Epuñán, Maráa José; Pino, Ana María; Valladares, Luis Emilio; Sierralta, Walter Daniel

    2008-06-01

    A cyclic peptide derived from the active domain of alpha-fetoprotein (AFP) significantly inhibited the proliferation of MCF7 cells stimulated with the epidermal growth factor (EGF) or estradiol (E2). The action of these three agents on cell growth was independent of the presence of calf serum in the culture medium. Our results demonstrated that the cyclic peptide interfered markedly with the regulation of MAPK by activated c-erbB2. The cyclic peptide showed no effect on the E2-stimulated release of matrix metalloproteinases 2 and 9 nor on the shedding of heparin-binding EGF into the culture medium. We propose that the AFP-derived cyclic peptide represents a valuable novel antiproliferative agent for treating breast cancer. PMID:18497971

  12. A cyclic peptide derived from alpha-fetoprotein inhibits the proliferative effects of the epidermal growth factor and estradiol in MCF7 cells.

    PubMed

    Torres, Cristian; Antileo, Elmer; Epuñán, Maráa José; Pino, Ana María; Valladares, Luis Emilio; Sierralta, Walter Daniel

    2008-06-01

    A cyclic peptide derived from the active domain of alpha-fetoprotein (AFP) significantly inhibited the proliferation of MCF7 cells stimulated with the epidermal growth factor (EGF) or estradiol (E2). The action of these three agents on cell growth was independent of the presence of calf serum in the culture medium. Our results demonstrated that the cyclic peptide interfered markedly with the regulation of MAPK by activated c-erbB2. The cyclic peptide showed no effect on the E2-stimulated release of matrix metalloproteinases 2 and 9 nor on the shedding of heparin-binding EGF into the culture medium. We propose that the AFP-derived cyclic peptide represents a valuable novel antiproliferative agent for treating breast cancer.

  13. [The effect of anti-human AFP serum for AFP producing stomach cancer xenotransplanted nude mice].

    PubMed

    Takahashi, Y; Akimoto, R; Mai, M; Sakai, T; Sudo, K

    1984-04-01

    The effect of anti-human alpha-fetoprotein (AFP) on growth, serum AFP levels and histological changes of two lines of AFP producing stomach cancer serially xenotransplanted in nude mice were examined. The efficacy of anti-human AFP antibody on tumor growth was observed specifically for the tumor producing AFP, but there was great difference on growth between two lines. The AFP levels of the serum disclosed a rapid decrease after administration of antibody and maintained as level of Ong/ml for a long period. On histopathologic examination, there were not observed any changes on the tumor cells and structure and necrotic change was not demonstrated. By the immunohistochemical examination (PAP method), anti-human AFP antibody was identified in tumor even 50 th days later after injection.

  14. Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

    PubMed Central

    Brenner, T; Beyth, Y; Abramsky, O

    1980-01-01

    The binding of myasthenia gravis antibody acetylcholine receptor (AcChoR) as measured in vitro by Radioimmunoassay with 125I-labeled alpha-bungarotoxin (alpha-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to alpha-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ii) selective addition of different components present in amniotic fluid and serum, including alpha-fetoprotein, to be radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of alpha-fetoprotein they contain; (iv) blocking of the alpha-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearnace of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of alpha-fetoprotein. PMID:6158053

  15. Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

    NASA Astrophysics Data System (ADS)

    Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin

    2015-04-01

    The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L- 1 and 0.054 μg L- 1 with the relative standard deviations (RSDs, n = 7, c = 5 μg L- 1) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2-50 μg L- 1. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications.

  16. First-trimester maternal serum alpha-fetoprotein as a marker for fetal chromosomal disorders. Dutch Working Party on Prenatal Diagnosis.

    PubMed

    Van Lith, J M

    1994-10-01

    We evaluated first-trimester maternal serum alpha-fetoprotein (MS-AFP) as a marker for fetal chromosomal disorders. The multicentre study was performed under the auspices of the Dutch Working Party on Prenatal Diagnosis. MS-AFP was measured in 2404 normal pregnancies and 72 chromosomally abnormal pregnancies. The median multiple of the normal median (MOM) in 32 Down's syndrome pregnancies was 0.83 with a 95 per cent confidence interval ranging from 0.60 to 1.04. The difference between the distributions of first-trimester MS-AFP in normal and Down's syndrome pregnancies was statistically significant (t-test: t = 2.34, P < 0.05). Thirty-one per cent of the Down's syndrome pregnancies were found below the tenth percentile. We found no difference between normal pregnancies and pregnancies with other chromosomal disorders (eight cases with trisomy 18, MOM = 1.26; seven cases with sex chromosome abnormalities, MOM = 1.07; 22 cases with a chromosomal mosaic pattern in chorionic villi, MOM = 1.08). We conclude that first-trimester MS-AFP can discriminate between normal and Down's syndrome pregnancies, but is not an effective marker. First-trimester MS-AFP has no value as a marker for other fetal chromosomal disorders. PMID:7534926

  17. Prolonged Survival in a Case of Chemotherapy-Sensitive Gastric Cancer That Produced Alpha-Fetoprotein and Protein Induced by Vitamin K Antagonist-II.

    PubMed

    Ogasawara, Naotaka; Takahashi, Emiko; Matsumoto, Tomoko; Amaike, Manami; Nohara, Mako; Nagao, Kazuhiro; Ebi, Masahide; Funaki, Yasushi; Sasaki, Makoto; Kasugai, Kunio

    2015-01-01

    The number of reported cases of alpha-fetoprotein (AFP)-producing gastric cancer has gradually increased, with a reported prevalence of 1.3-1.5% of all gastric cancer cases. However, reports of gastric cancer accompanied by elevated serum levels of both AFP and protein induced by vitamin K antagonist-II (PIVKA-II) are rare. The prognosis of AFP- and PIVKA-II-producing gastric cancer has been reported to be very poor because the tumor cells were considered to have a high malignant potential and the cancer progressed rapidly. We described a case of gastric cancer producing AFP and PIVKA-II in which chemotherapy was effective and resulted in prolonged survival, and these two tumor markers were useful for monitoring the treatment response. Routine health screening using upper abdominal ultrasonography revealed hepatic tumors in an apparently healthy 65-year-old man. Whole-body computed tomography (CT) revealed multiple hepatic tumors, and an esophagogastroduodenoscopy (EGD) revealed a Bormann type 3 tumor in the lower stomach. A biopsy specimen confirmed that the tumor was immunohistochemically positive for AFP, PIVKA-II, and human epidermal growth factor receptor 2. After chemotherapy, the gastric tumor appeared as a small elevated lesion on EGD, and CT revealed a remarkable reduction in the size of the metastatic liver tumors. The patient is still alive, 35 months after the initial chemotherapy. PMID:26034473

  18. Effect of increasing maximal aerobic exercise on serum gonadal hormones and alpha-fetoprotein in the luteal phase of professional female soccer players.

    PubMed

    Otağ, Aynur; Hazar, Muhsin; Otağ, İlhan; Beyleroğlu, Malik

    2016-03-01

    [Purpose] The performance of female athletes during their menstrual period has attracted the attention of researchers for many years. It is known that the menstrual period changes with exercise. Alpha-fetoprotein (AFP) is an oncofetal protein. In this study, the effect of maximal aerobic exercise in the luteal phase on some hormones and AFP in female athletes was researched. [Subjects and Methods] Twelve volunteers and healthy female footballers with normal menstrual cycles volunteered for this study as subjects. All the participants performed a shuttle run test. Blood samples were taken before, after, and one hour after exercise. Serum AFP, estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) values were measured using an auto analyzer and original kits. Heart rate measurements were performed before and after the exercise. [Results] AFP activity had significantly decreased after 1 h of recovery from the exercise in the female soccer players, and estrogen and LH activity had significantly increased immediately after the exercise. Progesterone activity had significantly decreased immediately after the exercise. FSH values had significantly increased immediately after the exercise. [Conclusion] The results of the present study show there were significant decreases in the values of AFP, which is a cancer parameter, 1 hour after the exercise. This result may be valuable in future physiotherapy studies on the relationship between exercise and cancer. PMID:27134362

  19. Characteristics of magnetic labeling on liver tumors with anti-alpha-fetoprotein-mediated Fe3O4 magnetic nanoparticles.

    PubMed

    Huang, Kai-Wen; Chieh, Jen-Jie; Horng, Herng-Er; Hong, Chin-Yih; Yang, Hong-Chang

    2012-01-01

    For preoperative and intraoperative detection of tumor distribution, numerous multimodal contrast agents, such as magnetic nanoparticles (MNPs) with several examination indicators, are currently in development. However, complex materials, configuration, and cost are required for multimodal contrast agents, accompanied by a high possibility of toxicity and low popularity in clinics. Nevertheless, the magnetic labeling of MNPs using bioprobes should be feasible not only in preoperative magnetic resonance imaging (MRI), but also in intraoperative examination based on other magnetic properties. In this study, anti-alpha-fetoprotein (AFP)-mediated Fe(3)O(4) MNPs, injected into mice with liver tumors, were used to examine the characteristics of magnetic labeling. Using MRI and scanning superconducting-quantum-interference-device biosusceptometry (SSB), based on alternating current (AC) susceptibility, the magnetic labeling occurred significantly on the first day post-injection of anti-AFP magnetic fluid (MF), and then decreased over time. However, for both MF without antibodies and an anti-carcinoembryonic antigen MF, no magnetic labeling occured on the first day of their respective post-injection. The favorable agreement indicates that magnetic labeling possesses two magnetic characteristics: distortion of the imaging field and AC susceptibility. In addition, the results of the biopsy tests, anti-AFP staining, and Prussian blue staining show the same dynamics as those of magnetic methodologies and prove that bound MNPs on tumor tissue are rotatable by an AC magnetic field to express AC susceptibility. Therefore, with the simple configuration of antibody-mediated MNPs, magnetic labeling is also feasible for intraoperative examinations using SSB with high mobility and sensitivity. PMID:22787394

  20. Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase

    PubMed Central

    Park, Joong-Won

    2016-01-01

    Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p< 0.001). Multivariate analysis showed that an AFP ratio > 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT. PMID:27304617

  1. Fullerol-fluorescein isothiocyanate-concanavalin agglutinin phosphorescent sensor for the detection of alpha-fetoprotein and forecast of human diseases

    NASA Astrophysics Data System (ADS)

    Liu, Jia-ming; Lin, Li-ping; Jiang, Shu-Lian; Cui, Ma Lin; Jiao, Li; Zhang, Xiao Yang; Zhang, Li-hong; Zheng, Zhi Yong; Lin, Xuan; Lin, Shao-qin

    2013-11-01

    Based on the reaction of the active -OH group in fullerol (F) with the dissociated -COOH group in fluorescein isothiocyanate (FITC) to form an F-FITC and the enhanced effect of N, N-dimethylaniline (DMA) on phosphorescence signal of F-FITC, a new phosphorescent labeling reagent (DMA-F-FITC) was developed. What's more, a phosphorescent sensor for the determination of alpha-fetoprotein variant (AFP-V) has been designed via the coupling technique of the high sensitivity for affinity adsorption-solid substrate-room temperature phosphorimetry (AA-SS-RTP) with the strong specificity reaction between DMA-F-FITC-Con A and AFP-V. The DMA-F-FITC increased the number of luminescent molecules in the biological target which improved the sensitivity of phosphorescent sensor. The proposed sensor was responsive, simple, selective and sensitive, and it has been applied to the determination of trace AFP-V in human serum and the forecast of human diseases using phosphorescence emission wavelength of F or FITC, with the results agreed well with those obtained by enzyme-linked immunoassay (ELISA). Meanwhile, the mechanisms for the labeling reaction and the sensing detection of AFP-V were discussed.

  2. A fluorescent molecularly-imprinted polymer gate with temperature and pH as inputs for detection of alpha-fetoprotein.

    PubMed

    Karfa, Paramita; Roy, Ekta; Patra, Santanu; Kumar, Deepak; Madhuri, Rashmi; Sharma, Prashant K

    2016-04-15

    In this work, we have reported a new approach on the use of stimuli-responsive molecularly imprinted polymer (MIP) for trace level sensing of alpha-fetoprotein (AFP), which is a well know cancer biomarker. The stimuli-responsive MIP is composed of three components, a thermo-responsive monomer, a pH responsive component (tyrosine derivative) and a highly fluorescent vinyl silane modified carbon dot. The synthesized AFP-imprinted polymer possesses excellent selectivity towards their template molecule and dual-stimuli responsive behavior. Along with this, the imprinted polymer was also explored as 'OR' logic gate with two stimuli (pH and temperature) as inputs. However, the non-imprinted polymers did not have such 'OR' gate property, which confirms the role of template binding. The imprinted polymer was also used for estimation of AFP in the concentration range of 3.96-80.0 ng mL(-1), with limit of detection (LOD) 0.42 ng mL(-1). The role of proposed sensor was successfully exploited for analysis of AFP in real human blood plasma, serum and urine sample.

  3. Improvement of insertion loss and quality factor of flexural plate-wave-based alpha-fetoprotein biosensor using groove-type reflective grating structures

    NASA Astrophysics Data System (ADS)

    Lin, Chang-Yu; Huang, I.-Yu; Lan, Je-Wei

    2013-01-01

    Conventional flexural plate-wave (FPW) transducers have limited applications in biomedical sensing due to their disadvantages such as high insertion loss and low quality factor. To overcome these shortcomings, we propose a FPW transducer on a low phase velocity insulator membrane (5-μm-thick SiO2) with a novel groove-type reflective grating structure design. Additionally, a cystamine self-assembly monolayer and a glutaraldehyde cross-linking layer are implemented on the backside of the FPW device to immobilize alpha-fetoprotein (AFP) antibody. A FPW-based AFP biosensor with low detection limit (5 ng/mL) can be achieved and used to measure the extreme low concentration of AFP antigen in human serum for early detection of hepatocellular carcinoma. The proposed FPW-based AFP biosensor also demonstrates a very high quality factor (206), low insertion loss (-40.854 dB), low operating frequency (6.388 MHz), and high sensing linearity (90.7%).

  4. Combined analysis of serum alpha-fetoprotein and MAGE-A3-specific cytotoxic T lymphocytes in peripheral blood for diagnosis of hepatocellular carcinoma.

    PubMed

    Cui, Zhuqingqing; Yu, Xin; Guo, Limin; Wei, Yuhua; Zheng, Shengmin; Li, Wenxia; Chen, Pengcheng; Zhu, Jiye; Peng, Jirun

    2013-01-01

    We investigated the feasibility of the combined detection of HLA-A2/MAGE-A3 epitope-specific cytotoxic T lymphocytes (CTLs) and serum alpha-fetoprotein (AFP) for specific diagnosis of hepatocellular carcinoma (HCC). We detected the frequency of MAGE-A3 epitopes (p112-120, KVAELVHFL) in spontaneous CTLs in the peripheral blood of HCC patients, liver cirrhosis patients, and healthy subjects with HLA-A2/polypeptide complex (pentamer) detection technology. Eighty-five HCC cases, 38 liver cirrhosis cases, and 50 healthy cases who were HLA-A2-positive were selected from 175 HCC patients, 80 patients with liver cirrhosis, and 105 healthy volunteers, respectively. The frequency of HLA-A2-specific MAGE-A3(+) CTLs in the HCC group was significantly higher than that in the other groups. Combined detection of MAGE-A3(+) CTL frequency and serum AFP value had a higher specificity than either of the two indicators alone. The pentamer technique is helpful in distinguishing benign lesions and malignant lesions in the liver. Combined with serum AFP, it can improve the diagnosis performance for HCC, especially for AFP-negative cancer. PMID:24427779

  5. Combined Analysis of Serum Alpha-Fetoprotein and MAGE-A3-Specific Cytotoxic T Lymphocytes in Peripheral Blood for Diagnosis of Hepatocellular Carcinoma

    PubMed Central

    Cui, Zhuqingqing; Yu, Xin; Guo, Limin; Wei, Yuhua; Zheng, Shengmin; Li, Wenxia; Chen, Pengcheng; Zhu, Jiye; Peng, Jirun

    2013-01-01

    We investigated the feasibility of the combined detection of HLA-A2/MAGE-A3 epitope-specific cytotoxic T lymphocytes (CTLs) and serum alpha-fetoprotein (AFP) for specific diagnosis of hepatocellular carcinoma (HCC). We detected the frequency of MAGE-A3 epitopes (p112–120, KVAELVHFL) in spontaneous CTLs in the peripheral blood of HCC patients, liver cirrhosis patients, and healthy subjects with HLA-A2/polypeptide complex (pentamer) detection technology. Eighty-five HCC cases, 38 liver cirrhosis cases, and 50 healthy cases who were HLA-A2-positive were selected from 175 HCC patients, 80 patients with liver cirrhosis, and 105 healthy volunteers, respectively. The frequency of HLA-A2-specific MAGE-A3+ CTLs in the HCC group was significantly higher than that in the other groups. Combined detection of MAGE-A3+ CTL frequency and serum AFP value had a higher specificity than either of the two indicators alone. The pentamer technique is helpful in distinguishing benign lesions and malignant lesions in the liver. Combined with serum AFP, it can improve the diagnosis performance for HCC, especially for AFP-negative cancer. PMID:24427779

  6. Clinical studies on the radioimmunodetection of tumors containing alpha-fetoprotein.

    PubMed

    Goldenberg, D M; Kim, E E; Deland, F; Spremulli, E; Nelson, M O; Gockerman, J P; Primus, F J; Corgan, R L; Alpert, E

    1980-05-15

    This study reports the use of radiolabeled antibodies to alpha-fetoprotein for the detection and localization of hepatocellular and germ cell carcinomas. Twelve patients with histories of histologically-confirmed neoplasia received a total dose between 1.0 and 4.4 mCi of 131I-labeled goat IgG prepared against human alpha-fetoprotein. Total-body photoscans were taken with a gamma scintillation camera at various intervals after injection of the radioactive antibody. Computer subtraction of radioactive technetium background images from the antibody 131I scans permitted the visualization of all tumor sites known to be present in 4 patients with either primary hepatocellular cancer or metastatic germ cell carcinoma of the testis. In contrast to the results with the specific antibody, radioactive normal goat IgG given to one of these patients with metastatic embryonal carcinoma of the testis failed to show equivalent localization. Among 8 patients with diverse neoplasms not believed to contain alpha-fetoprotein, 5 of 19 tumor sites showed radioactive antibody accretion, although significantly less than in the patients with liver or testicular cancer. Circulating antigen levels of up to 15,000 ng per milliliter did not prevent successful tumor imaging after intravenous injection of the radioantibody. This investigation indicates that alpha-fetoprotein-containing tumors can be detected and localized in vivo by the method of radioimmunodetection.

  7. Clinical studies on the radioimmunodetection of tumors containing alpha-fetoprotein

    SciTech Connect

    Goldenberg, D.M.; Kim, E.E.; Deland, F.; Spremulli, E.; Nelson, M.O.; Gockerman, J.P.; Primus, F.J.; Corgan, R.L.; Alpert, E.

    1980-05-15

    This study reports the use of radiolabeled antibodies to alpha-fetoprotein for the detection and localization of hepatocellular and germ cell carcinomas. Twelve patients with histories of histologically-confirmed neoplasia received a total dose between 1.0 and 4.4 mCi of /sup 131/I-labeled goat IgG prepared against human alpha-fetoprotein. Total-body photoscans were taken with a gamma scintillation camera at various intervals after injection of the radioactive antibody. Computer subtraction of radioactive technetium background images from the antibody /sup 131/I scans permitted the visualization of all tumor sites known to be present in 4 patients with either primary hepatocellular cancer or metastatic germ cell carcinoma of the testis. Among 8 patients with diverse neoplasms not believed to contain alpha-fetoprotein, 5 of 19 tumor sites showed radioactive antibody accretion, although significantly less than in the patients with liver or testicular cancer. This investigation indicates that alpha-fetoprotein-containing tumors can be detected and localized in vivo by the method of radioimmunodetection.

  8. Pineal ganglioglioma in a patient with familial basal ganglia calcification and elevated serum alpha-fetoprotein: case report.

    PubMed

    Tokoro, K; Chiba, Y; Ohtani, T; Abe, H; Yagishita, S

    1993-09-01

    Pineal ganglioglioma was diagnosed in a 36-year-old man with familial basal ganglia calcification and elevated serum alpha-fetoprotein. The patient was treated surgically with a good result. Only four other cases of this tumor have been reported. His 38-year-old brother also showed basal ganglia calcification and elevated serum chorionic gonadotropin as well as alpha-fetoprotein. Familial basal ganglia calcification with elevated serum alpha-fetoprotein in a nonhepatic benign condition is rare. The pathogenesis of these conditions is discussed. PMID:7692346

  9. Rapid and sensitive lateral flow immunoassay method for determining alpha fetoprotein in serum using europium (III) chelate microparticles-based lateral flow test strips.

    PubMed

    Liang, Rong-Liang; Xu, Xu-Ping; Liu, Tian-Cai; Zhou, Jian-Wei; Wang, Xian-Guo; Ren, Zhi-Qi; Hao, Fen; Wu, Ying-Song

    2015-09-01

    Alpha-fetoprotein (AFP), a primary marker for many diseases including various cancers, is important in clinical tumor diagnosis and antenatal screening. Most immunoassays provide high sensitivity and accuracy for determining AFP, but they are expensive, often complex, time-consuming procedures. A simple and rapid point-of-care system that integrates Eu (III) chelate microparticles with lateral flow immunoassay (LFIA) has been developed to determine AFP in serum with an assay time of 15 min. The approach is based on a sandwich immunoassay performed on lateral flow test strips. A fluorescence strip reader was used to measure the fluorescence peak heights of the test line (HT) and the control line (HC); the HT/HC ratio was used for quantitation. The Eu (III) chelate microparticles-based LFIA assay exhibited a wide linear range (1.0-1000 IU mL(-1)) for AFP with a low limit of detection (0.1 IU mL(-1)) based on 5ul of serum. Satisfactory specificity and accuracy were demonstrated and the intra- and inter-assay coefficients of variation (CV) for AFP were both <10%. Furthermore, in the analysis of human serum samples, excellent correlation (n = 284, r = 0.9860, p < 0.0001) was obtained between the proposed method and a commercially available CLIA kit. Results indicated that the Eu (III) chelate microparticles-based LFIA system provided a rapid, sensitive and reliable method for determining AFP in serum, indicating that it would be suitable for development in point-of-care testing.

  10. Rapid and sensitive lateral flow immunoassay method for determining alpha fetoprotein in serum using europium (III) chelate microparticles-based lateral flow test strips.

    PubMed

    Liang, Rong-Liang; Xu, Xu-Ping; Liu, Tian-Cai; Zhou, Jian-Wei; Wang, Xian-Guo; Ren, Zhi-Qi; Hao, Fen; Wu, Ying-Song

    2015-09-01

    Alpha-fetoprotein (AFP), a primary marker for many diseases including various cancers, is important in clinical tumor diagnosis and antenatal screening. Most immunoassays provide high sensitivity and accuracy for determining AFP, but they are expensive, often complex, time-consuming procedures. A simple and rapid point-of-care system that integrates Eu (III) chelate microparticles with lateral flow immunoassay (LFIA) has been developed to determine AFP in serum with an assay time of 15 min. The approach is based on a sandwich immunoassay performed on lateral flow test strips. A fluorescence strip reader was used to measure the fluorescence peak heights of the test line (HT) and the control line (HC); the HT/HC ratio was used for quantitation. The Eu (III) chelate microparticles-based LFIA assay exhibited a wide linear range (1.0-1000 IU mL(-1)) for AFP with a low limit of detection (0.1 IU mL(-1)) based on 5ul of serum. Satisfactory specificity and accuracy were demonstrated and the intra- and inter-assay coefficients of variation (CV) for AFP were both <10%. Furthermore, in the analysis of human serum samples, excellent correlation (n = 284, r = 0.9860, p < 0.0001) was obtained between the proposed method and a commercially available CLIA kit. Results indicated that the Eu (III) chelate microparticles-based LFIA system provided a rapid, sensitive and reliable method for determining AFP in serum, indicating that it would be suitable for development in point-of-care testing. PMID:26388387

  11. Alpha-fetoprotein level as a biomarker of liver fibrosis status: a cross-sectional study of 619 consecutive patients with chronic hepatitis B

    PubMed Central

    2014-01-01

    Background Hepatitis B virus (HBV) infection is a serious public health problem worldwide. This study aimed to investigate the relationship between serum alpha-fetoprotein (AFP) levels and pathological stages of liver biopsy in patients with chronic hepatitis B (CHB). Methods The study included 619 patients who were diagnosed with CHB from March 2005 to December 2011. AFP levels were measured by electrochemiluminescence. Liver biopsy samples were classified into five levels of inflammation (G) and fibrosis (S) stages, according to the Chinese guidelines for prevention and treatment of viral hepatitis. Two multivariable ordinal regression models were performed to determine associations between AFP, GGT, and APRI (AST/PLT ratio) and stages of inflammation and fibrosis. Results Significant positive and moderate correlations were shown between AFP levels and inflammation stages and between AFP levels and fibrosis stages (ρ = 0.436 and 0.404, p < 0.001). Median values of AFP at liver fibrosis stages S0-1, S2, S3, and S4 were 3.0, 3.4, 5.4, and 11.3 ng/ml, respectively, and median APRI (AST/PLT ratio) was 0.41. Receiver operating characteristic (ROC) curve analyses revealed that the areas under the curves (AUCs) were 0.685, 0.727, and 0.755 (all p <0.001) for judging inflammation stages of G ≥ 2, G ≥ 3, G = 4 by AFP; and 0.691, 0.717, and 0.718 (all p <0.001) for judging fibrosis stages of S ≥ 2, S ≥ 3, and S = 4 by AFP. APRI levels showed significant positive and moderate correlations with inflammation stages (ρ = 0.445, p < 0.001). AST, GGT, and APRI levels showed significant positive but very weak to weak correlations with fibrosis stages (ρ = 0.137, 0.237, 0.281, p < 0.001). Conclusions Serum AFP levels increased as pathological levels of inflammation and fibrosis increased in CHB patients. Our data showed the clinical significance of serum AFP levels in diagnosing liver inflammation and fibrosis. Assessment of liver pathology may be improved by creating

  12. Liver transplantation for hepatocellular carcinoma in Ireland: Pre-operative alpha-fetoprotein predicts tumour recurrence in a 14-year single-centre national experience

    PubMed Central

    O’Connor, Donal B; Burke, John P; Hegarty, John; McCormick, Aiden P; Nolan, Niamh; Hoti, Emir; Maguire, Donal; Geoghegan, Justin; Traynor, Oscar

    2016-01-01

    AIM: To examine the results of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) in Ireland over a 14-year period. METHODS: Cases of HCC receiving OLT between January 1995 and September 2009 in the Irish Liver Transplant Unit were reviewed from a prospectively maintained database. Outcome measures included overall and recurrence free survival, alpha-fetoprotein (AFP) and tumour pathological features. RESULTS: On explant pathology, 57 patients had HCC. The median follow-up time was 42.7 mo. The overall 1, 3 and 5 years survival was 87.7%, 72.1% and 72.4%. There was no difference in survival when compared to patients undergoing OLT without malignancy. The tumour recurrence rate was 14%. The Milan criteria were exceeded in 32% of cases but this did not predict overall survival or recurrence. On multivariate analysis pre-operative AFP > 100 ng/mL was an independent risk factor for recurrence (RR = 5.2, CI: 1.1-24.3, P = 0.036). CONCLUSION: Patients undergoing OLT for HCC had excellent survival even when conventional listing criteria were exceeded. Pre-operative AFP predicts recurrence independent of tumour size and its role in selection criteria should be investigated in larger studies. PMID:27358785

  13. Ru(bpy)32+/nanoporous silver-based electrochemiluminescence immunosensor for alpha fetoprotein enhanced by gold nanoparticles decorated black carbon intercalated reduced graphene oxide

    PubMed Central

    Zhu, Wenjuan; Lv, Xiaohui; Wang, Qi; Ma, Hongmin; Wu, Dan; Yan, Tao; Hu, Lihua; Du, Bin; Wei, Qin

    2016-01-01

    A highly sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was proposed for the quantitative determination of alpha fetoprotein (AFP) using gold nanoparticles decorated black carbon intercalated reduced graphene oxide (Au-rGO@CB) as sensing platform and nanoporous silver (NPS) loaded Ru(bpy)32+ as labels. In this work, intercalation of CB inhibited the accumulation of rGO and Au-rGO@CB was firstly used to immobilize primary antibody (Ab1) in ECL system. NPS prepared by the dealloying of binary alloy has high pore volume and surface areas, which was used to load amount of secondary antibodies (Ab2) and Ru(bpy)32+, which could greatly enhance the ECL intensity. Under optimal conditions, the designed immunosensor exhibited wider linear range from 0.0001 to 30 ng/mL with a relative lower detection limit of 33 fg/mL for AFP detection. Overall, the designed immunosensor exhibited high sensitivity and selectivity, good repeatability and stability. This proposed method provided a potential application for clinical monitoring of AFP. PMID:26829062

  14. Highly sensitive electrochemical immunosensor for the detection of alpha fetoprotein based on PdNi nanoparticles and N-doped graphene nanoribbons.

    PubMed

    Li, Na; Ma, Hongmin; Cao, Wei; Wu, Dan; Yan, Tao; Du, Bin; Wei, Qin

    2015-12-15

    An ultrasensitive sandwich-type electrochemical immunosensor was designed for the quantitative detection of alpha fetoprotein (AFP). The β-cyclodextrins functionalized graphene sheets (CD-GS) were used as the sensing matrix for immobilizing adamantine-1-carboxylic acid functionalized primary anti-AFP (ADA-Ab1) and enhanced the electron transfer. PdNi alloy nanoparticles decorated N-doped graphene nanoribbons (PdNi/N-GNRs) were used as labels of secondary anti-AFP (Ab2), and PdNi alloy nanoparticles (PdNi NPs) exhibited high catalytic performance towards the reduction of H2O2. Meanwhile, with good dispersion, large specific surface area and good catalytic performance, N-doped graphene nanoribbons (N-GNRs) significantly amplified the electrochemical signal. Under the optimal conditions, the electrochemical immunosensor exhibited a wide linear range of 0.0001-16 ng/mL with a low detection limit of 0.03 pg/mL. Additionally, the proposed immunosensor showed high specificity, good reproducibility and long-term stability, which have promising application in bioassay analysis.

  15. Facile fabrication of an ultrasensitive sandwich-type electrochemical immunosensor for the quantitative detection of alpha fetoprotein using multifunctional mesoporous silica as platform and label for signal amplification.

    PubMed

    Wang, Yulan; Li, Xiaojian; Cao, Wei; Li, Yueyun; Li, He; Du, Bin; Wei, Qin

    2014-11-01

    A novel and ultrasensitive sandwich-type electrochemical immunosensor was designed for the quantitative detection of alpha fetoprotein (AFP) using multifunctional mesoporous silica (MCM-41) as platform and label for signal amplification. MCM-41 has high specific surface area, high pore volume, large density of surface silanol groups (SiOH) and good biocompatibility. MCM-41 functionalized with 3-aminopropyltriethoxysilane (APTES), gold nanoparticles (Au NPs) and toluidine blue (TB) could enhance electrochemical signals. Moreover, primary antibodies (Ab1) and secondary antibodies (Ab2) could be effectively immobilized onto the multifunctional MCM-41 by the interaction between Au NPs and amino groups (-NH2) on antibodies. Using multifunctional MCM-41 as a platform and label could greatly simplify the fabrication process and result in a high sensitivity of the designed immunosensor. Under optimal conditions, the designed immunosensor exhibited a wide liner range from 10(-4) ng/mL to 10(3) ng/mL with a low detection limit of 0.05 pg/mL for AFP. The designed immunosensor showed acceptable selectivity, reproducibility and stability, which could provide potential applications in clinical monitoring of AFP.

  16. Facile fabrication of a silicon nanowire sensor by two size reduction steps for detection of alpha-fetoprotein biomarker of liver cancer

    NASA Astrophysics Data System (ADS)

    Binh Pham, Van; ThanhTung Pham, Xuan; Nhat Khoa Phan, Thanh; Thanh Tuyen Le, Thi; Chien Dang, Mau

    2015-12-01

    We present a facile technique that only uses conventional micro-techniques and two size-reduction steps to fabricate wafer-scale silicon nanowire (SiNW) with widths of 200 nm. Initially, conventional lithography was used to pattern SiNW with 2 μm width. Then the nanowire width was decreased to 200 nm by two size-reduction steps with isotropic wet etching. The fabricated SiNW was further investigated when used with nanowire field-effect sensors. The electrical characteristics of the fabricated SiNW devices were characterized and pH sensitivity was investigated. Then a simple and effective surface modification process was carried out to modify SiNW for subsequent binding of a desired receptor. The complete SiNW-based biosensor was then used to detect alpha-fetoprotein (AFP), one of the medically approved biomarkers for liver cancer diagnosis. Electrical measurements showed that the developed SiNW biosensor could detect AFP with concentrations of about 100 ng mL-1. This concentration is lower than the necessary AFP concentration for liver cancer diagnosis.

  17. Utility-based criteria for selecting patients with hepatocellular carcinoma for liver transplantation: A multicenter cohort study using the alpha-fetoprotein model as a survival predictor.

    PubMed

    Vitale, Alessandro; Farinati, Fabio; Burra, Patrizia; Trevisani, Franco; Giannini, Edoardo G; Ciccarese, Francesca; Piscaglia, Fabio; Rapaccini, Gian Lodovico; Di Marco, Mariella; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Cabibbo, Giuseppe; Felder, Martina; Sacco, Rodolfo; Morisco, Filomena; Missale, Gabriele; Foschi, Francesco Giuseppe; Gasbarrini, Antonio; Svegliati Baroni, Gianluca; Virdone, Roberto; Chiaramonte, Maria; Spolverato, Gaya; Cillo, Umberto

    2015-10-01

    The lifetime utility of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is still controversial. The aim of this study was to ascertain when LT is cost-effective for HCC patients, with a view to proposing new transplant selection criteria. The study involved a real cohort of potentially transplantable Italian HCC patients (n = 2419 selected from the Italian Liver Cancer group database) who received nontransplant therapies. A non-LT survival analysis was conducted, the direct costs of therapies were calculated, and a Markov model was used to compute the cost utility of LT over non-LT therapies in Italian and US cost scenarios. Post-LT survival was calculated using the alpha-fetoprotein (AFP) model on the basis of AFP values and radiological size and number of nodules. The primary endpoint was the net health benefit (NHB), defined as LT survival benefit in quality-adjusted life years minus incremental costs (US $)/willingness to pay. The calculated median cost of non-LT therapies per patient was US $53,042 in Italy and US $62,827 in the United States. On Monte Carlo simulation, the NHB of LT was always positive for AFP model values ≤ 3 and always negative for values > 7 in both countries. A multivariate model showed that nontumor variables (patient's age, Child-Turcotte-Pugh [CTP] class, and alternative therapies) had the potential to shift the AFP model threshold of LT cost-ineffectiveness from 3 to 7. LT proved always cost-effective for HCC patients with AFP model values ≤ 3, whereas the cost-ineffectiveness threshold ranged between 3 and 7 using nontumor variables. PMID:26183802

  18. Utility-based criteria for selecting patients with hepatocellular carcinoma for liver transplantation: A multicenter cohort study using the alpha-fetoprotein model as a survival predictor.

    PubMed

    Vitale, Alessandro; Farinati, Fabio; Burra, Patrizia; Trevisani, Franco; Giannini, Edoardo G; Ciccarese, Francesca; Piscaglia, Fabio; Rapaccini, Gian Lodovico; Di Marco, Mariella; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Cabibbo, Giuseppe; Felder, Martina; Sacco, Rodolfo; Morisco, Filomena; Missale, Gabriele; Foschi, Francesco Giuseppe; Gasbarrini, Antonio; Svegliati Baroni, Gianluca; Virdone, Roberto; Chiaramonte, Maria; Spolverato, Gaya; Cillo, Umberto

    2015-10-01

    The lifetime utility of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is still controversial. The aim of this study was to ascertain when LT is cost-effective for HCC patients, with a view to proposing new transplant selection criteria. The study involved a real cohort of potentially transplantable Italian HCC patients (n = 2419 selected from the Italian Liver Cancer group database) who received nontransplant therapies. A non-LT survival analysis was conducted, the direct costs of therapies were calculated, and a Markov model was used to compute the cost utility of LT over non-LT therapies in Italian and US cost scenarios. Post-LT survival was calculated using the alpha-fetoprotein (AFP) model on the basis of AFP values and radiological size and number of nodules. The primary endpoint was the net health benefit (NHB), defined as LT survival benefit in quality-adjusted life years minus incremental costs (US $)/willingness to pay. The calculated median cost of non-LT therapies per patient was US $53,042 in Italy and US $62,827 in the United States. On Monte Carlo simulation, the NHB of LT was always positive for AFP model values ≤ 3 and always negative for values > 7 in both countries. A multivariate model showed that nontumor variables (patient's age, Child-Turcotte-Pugh [CTP] class, and alternative therapies) had the potential to shift the AFP model threshold of LT cost-ineffectiveness from 3 to 7. LT proved always cost-effective for HCC patients with AFP model values ≤ 3, whereas the cost-ineffectiveness threshold ranged between 3 and 7 using nontumor variables.

  19. Persistent increase in alpha-fetoprotein level in a patient without underlying liver disease who underwent curative resection of hepatocellular carcinoma. A case report and review of the literature

    PubMed Central

    2012-01-01

    Introduction Alpha-fetoprotein (AFP) is an oncofetal protein produced by hepatocellular carcinoma (HCC). AFP level can also be elevated in other neoplastic or non-neoplastic conditions. An elevated AFP level has high diagnostic significance for HCC; at a level of >200 ng/mL, the probability of HCC is >90%. The aim of the present paper is to report a patient who underwent curative resection of HCC, who had a persistently elevated AFP level postoperatively but did not develop recurrence during a 2-year follow-up period. A review of the literature is also presented. Case report An 82-year-old male was referred following a computed tomography scan showing a 160 mm diameter mass in the left lobe of the liver. This huge mass was diagnosed as HCC, arising in the absence of cirrhosis or viral hepatitis. After tumor removal, the patient’s high AFP level persisted for 2 years. Conclusion As steatosis was the only pathological change in the remnant liver, this may have caused the persistently elevated AFP level in this patient. PMID:22559879

  20. Diagnostic Performance of Alpha-Fetoprotein, Protein Induced by Vitamin K Absence, Osteopontin, Dickkopf-1 and Its Combinations for Hepatocellular Carcinoma

    PubMed Central

    Jang, Eun Sun; Jeong, Sook-Hyang; Kim, Jin-Wook; Choi, Yun Suk; Leissner, Philippe; Brechot, Christian

    2016-01-01

    Background & Aims Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. As complementary biomarkers, protein induced by vitamin K absence (PIVKA-II), osteopontin (OPN), and Dickkopf-1 (DKK-1) have been proposed. This study aimed to perform a head-to-head comparison of the diagnostic performance of AFP, PIVKA-II, OPN and DKK-1 as single or in combination to seek the best biomarker or panel, and to investigate the clinical factors affecting their performance. Methods Using 401 stored plasma samples obtained from 208 HCC patients and 193 liver cirrhosis control patients, plasma AFP, PIVKA-II, OPN and DKK-1 levels were measured by ELISA, and receiver operating characteristic curve analyses were performed for each biomarker and for every combination of two to four markers. Results Of the four biomarkers, AFP showed the highest area under the curve (0.786). The sensitivity and specificity for each single biomarker was 62% and 90.2% (AFP>20 ng/mL), 51.0% and 91.2% (PIVKA-II>10 ng/mL), 46.2% and 80.3% (OPN>100 ng/mL), and 50.0% and 80.8% (DKK-1>500 pg/mL), respectively. Among the combinations of two biomarkers, AFP>20 ng/mL or DKK-1>500 pg/mL showed the best diagnostic performance (sensitivity 78.4%, specificity 72.5%). Triple or quadruple combination did not improve the diagnostic performance further. The patient’s age, etiology and tumor invasiveness of HCC affected the performance of each marker. Conclusions AFP was the most useful single biomarker for HCC diagnosis, and the combined measurement of AFP and DKK-1 could maximize the diagnostic yield. Clinical decision should be based on the consideration of various factors affecting the diagnostic performance of each biomarker. Efforts to seek novel HCC biomarkers should be continued. PMID:26986465

  1. Three-dimensional tumor volume and serum alpha-fetoprotein are predictors of hepatocellular carcinoma recurrence after liver transplantation: refined selection criteria.

    PubMed

    Kashkoush, Samy; El Moghazy, Walid; Kawahara, Toshiyasu; Gala-Lopez, Boris; Toso, Christian; Kneteman, Norman M

    2014-06-01

    Total tumor volume (TTV), as a better predictor of hepatocellular carcinoma (HCC) recurrence after liver transplant, has been explored by our center. Some tumors are not typically spherical but rather ellipsoid or spheroid, and calculating their TTV based on one dimension only may overestimate their volume and exclude them from candidacy for transplantation. Our aim was to study the actual tumor volume (ATV) calculated using the ellipsoid formula and assess its impact on recurrence. HCC patients transplanted between 1990 and 2010 at University of Alberta Hospital were analyzed. Tumor volumes were calculated using both formulas: [(4/3) πr(3)] (r = max. radius) and [(4/3) πabc] (a, b, c = the 3 radiuses). A total of 115 patients were included with a mean follow-up of 4.99 ± 4.23 yr. Five-yr recurrence-free survival was 79.8%. Univariate analysis for predictors of recurrence included: maximum tumor diameter, ATV, TTV, and alpha-fetoprotein (AFP) ≥ 400 ng/mL. Multivariate analysis showed that ATV and AFP ≥ 400 ng/mL were the only predictors of recurrence. Combining both variables provides better predication of recurrence with accuracy that exceeds 80%. Three-dimensional calculation of tumor volume is of critical importance for the group of patients with ellipsoid tumors where volumes are overestimated with the spherical formula and could lead to inappropriate exclusion from transplant. PMID:24708263

  2. A novel electrochemical immunosensor using β-cyclodextrins functionalized silver supported adamantine-modified glucose oxidase as labels for ultrasensitive detection of alpha-fetoprotein.

    PubMed

    Gao, Jian; Ma, Hongmin; Lv, Xiaohui; Yan, Tao; Li, Na; Cao, Wei; Wei, Qin

    2015-09-17

    In this work, a novel sandwich-type electrochemical immunosensor based on host-guest interaction was fabricated for the detection of alpha-fetoprotein (AFP). Due to the large specific surface area of multiwalled carbon nanotubes and the unique supramolecular recognition ability of β-cyclodextrins, ferrocenecarboxylic acid (Fc) was incorporated into this sensor platform by host-guest interaction to generate an electrochemical signal. And β-cyclodextrins functionalized silver supported adamantine-modified glucose oxidase (GOD-CD-Ag), was used as a label to improve the analytical performance of the immunosensor by the dual amplification strategy. The obtained GOD-CD-Ag conjugates could convert glucose into gluconic acid with the formation of hydrogen peroxide (H2O2). And then silver nanoparticles could in situ catalyze the reduction of the generated H2O2, dramatically improving the oxidation reaction of Fc. The developed immunosensor shows a wide linear calibration range from 0.001 to 5.0 ng/mL with a low detection limit (0.2 pg/mL) for the detection of AFP. The method, with ideal reproducibility and selectivity, has a wide application prospect in clinical research.

  3. A novel electrochemical immunosensor using β-cyclodextrins functionalized silver supported adamantine-modified glucose oxidase as labels for ultrasensitive detection of alpha-fetoprotein.

    PubMed

    Gao, Jian; Ma, Hongmin; Lv, Xiaohui; Yan, Tao; Li, Na; Cao, Wei; Wei, Qin

    2015-09-17

    In this work, a novel sandwich-type electrochemical immunosensor based on host-guest interaction was fabricated for the detection of alpha-fetoprotein (AFP). Due to the large specific surface area of multiwalled carbon nanotubes and the unique supramolecular recognition ability of β-cyclodextrins, ferrocenecarboxylic acid (Fc) was incorporated into this sensor platform by host-guest interaction to generate an electrochemical signal. And β-cyclodextrins functionalized silver supported adamantine-modified glucose oxidase (GOD-CD-Ag), was used as a label to improve the analytical performance of the immunosensor by the dual amplification strategy. The obtained GOD-CD-Ag conjugates could convert glucose into gluconic acid with the formation of hydrogen peroxide (H2O2). And then silver nanoparticles could in situ catalyze the reduction of the generated H2O2, dramatically improving the oxidation reaction of Fc. The developed immunosensor shows a wide linear calibration range from 0.001 to 5.0 ng/mL with a low detection limit (0.2 pg/mL) for the detection of AFP. The method, with ideal reproducibility and selectivity, has a wide application prospect in clinical research. PMID:26398422

  4. Gold-silver-graphene hybrid nanosheets-based sensors for sensitive amperometric immunoassay of alpha-fetoprotein using nanogold-enclosed titania nanoparticles as labels.

    PubMed

    Su, Biling; Tang, Dianping; Li, Qunfang; Tang, Juan; Chen, Guonan

    2011-04-29

    A new sandwich-type electrochemical immunosensor with enhanced sensitivity was developed for detection of alpha-fetoprotein (AFP, as a model analyte) in biological fluids by using nanogold-enclosed titania nanoparticle (AuTi)-labeled secondary antibody on a gold-silver-graphene hybrid nanosheet (AuAgGP)-functionalized glassy carbon electrode (GCE). The presence of the AuAgGP nanosheets not only enhanced the immobilized amount of biomolecules, but also improved the electrochemical properties of the immunosensor. With the aid of AuTi nanolabels, the electrochemical signal was greatly amplified in comparison with pure nanogold or titania-based labels. Under optimal conditions, the sensitivity and dynamic range of the immunosensor were evaluated by using the labeled horseradish peroxidase on the AuTi as trace and H(2)O(2) as enzyme substrate, and exhibited a wide dynamic range of 0.001-200 ng mL(-1) with a low detection limit (LOD) of 0.5 pg mL(-1) AFP (at 3σ). Both the intra- and inter-assay coefficients of variation were less than 10%. The current of the immunosensor at 13th day was as much as 90% of the initial current. In addition, the methodology was evaluated for 8 positive serum specimens obtained from hepatocarcinoma patients and 19 negative sera, and validated with the commercially available Roche 2010 Electrochemiluminescent (ECL) Automatic Analyzer. No significant differences at the 95% confidence level were encountered between two methods.

  5. Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis

    PubMed Central

    Jeon, Yejoo; Jang, Eun Sun; Choi, Yun Suk; Kim, Jin-Wook; Jeong, Sook-Hyang

    2016-01-01

    Background/Aims Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. Methods We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve. Results Plasma GPC3 levels in HCC patients were very low (0–3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729. Conclusion The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted. PMID:27729630

  6. Prenatal screening using maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol: two-year experience in a health maintenance organization.

    PubMed

    McDuffie, R S; Haverkamp, A D; Stark, C F; Haverkamp, C; Barth, C K

    1996-01-01

    The objective of this study was to evaluate a 2-year experience in a health maintenance organization with mid-trimester maternal serum screening with alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and unconjugated estriol (UE) as a screen for fetal Down's syndrome. Women at 15-20 weeks gestation were offered triple marker screening. A patient-specific second trimester risk of 1:295 for Down's syndrome was used as a threshold for referral. Women at risk for trisomy 18 were identified by a protocol with fixed low cutoffs. The AFP threshold for referral for neural tube defects (NTD) was 2.0 multiples of the median (MoM). Patients at risk were offered ultrasonography, genetic counseling, and prenatal diagnosis. A total of 6,474 samples were drawn. The initial screen positive rate for Down's syndrome was 7.1%. After ultrasound evaluation, 351 (5.7%) of the remaining 6,197 women were still at risk for Down's syndrome. After genetic counseling, 292 (4.7%) women underwent prenatal diagnosis. Overall, 12 of 16 (75%) cases of Down's syndrome were detected antenatally by triple marker screening. Using AFP alone, only 3 of 14 (21%) cases of Down's syndrome in women under 35 years would have been detected. We detected 1 abnormal karyotype (including one 45, X) for every 22 amniocenteses performed for abnormal Down's syndrome screening. For trisomy 18, 13 women (0.2%) were at risk and, of these, 3 cases were diagnosed. All 6 cases of NTD during the study period were detected by AFP after identifying 3.8% of women as at risk. In conclusion, in the setting of a health maintenance organization where abnormal screening tests were managed by a single referral center, triple marker screening was effective not only for screening for fetal Down's syndrome, but also for trisomy 18 and NTD. PMID:8796771

  7. Construction of Expression Vector for Anti-Alpha-Fetoprotein Gene and Its Inhibition Effects on Alpha-Fetoprotein Positive Hepg2 Cells

    NASA Astrophysics Data System (ADS)

    Wang, Ze; Zhang, Hui

    As research previously demonstrated, suppression of AFP expression or its biological activities might inhibit the proliferation of AFP positive human hepatocellular carcinoma cells. In this study, we constructed an anti-AFP gene vector and transfected it to HepG2 cells. RT-PCR showed AFP gene expression in the transfected cells was reduced. MTT assay suggested the proliferation of the transfected cells was also inhibited comparing with the untransfected cells. This result provides a new insight into AFP as the target for preventing and treating hepatocellular carcinoma.

  8. Maternal serum alpha-fetoprotein (MSAFP) patient-specific risk reporting: its use and misuse.

    PubMed

    Macri, J N; Kasturi, R V; Krantz, D A; Cook, E J; Larsen, J W

    1990-03-01

    Fundamental to maternal serum alpha-fetoprotein screening is the clinical utility of the laboratory report. It follows that the scientific form of expression in that report is vital. Professional societies concur that patient-specific risk reporting is the preferred form. However, some intermediate steps being taken to calculate patient-specific risks are invalid because of the erroneous assumption that multiples of the median (MoMs) represent an interlaboratory common currency. The numerous methods by which MoMs may be calculated belie the foregoing assumption. PMID:1689955

  9. Alpha fetoprotein

    MedlinePlus

    ... Palm Beach, FL. Review Provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Birth Defects Cirrhosis Hepatitis Liver Cancer Neural Tube Defects Ovarian Cancer Prenatal Testing Spina Bifida ...

  10. Evaluation of the diagnostic value of alpha-l-fucosidase, alpha-fetoprotein and thymidine kinase 1 with ROC and logistic regression for hepatocellular carcinoma

    PubMed Central

    Zhang, Shi-Yan; Lin, Bi-Ding; Li, Bu-Ren

    2015-01-01

    The purpose of this study was to evaluate the diagnostic efficiency for hepatocellular carcinoma (HCC) with the combined analysis of alpha-l-fucosidase (AFU), alpha-fetoprotein (AFP) and thymidine kinase 1 (TK1). Serum levels of AFU, AFP and TK1 were measured in: 116 patients with HCC, 109 patients with benign hepatic diseases, and 104 normal subjects. The diagnostic value was analyzed using the logistic regression equation and receiver operating characteristic curves (ROC). Statistical distribution of the three tested tumor markers in every group was non-normally distributed (Kolmogorov–Sminov test, Z = 0.156–0.517, P < 0.001). The serum levels of AFP and TK1 in patients with HCC were significantly higher than those in patients with benign hepatic diseases (Mann–Whitney U test, Z = −8.570 to –5.943, all P < 0.001). However, there was no statistically significant difference of AFU between these two groups (Mann–Whitney U test, Z = −1.820, P = 0.069). The levels of AFU were significantly higher in patients with benign hepatic diseases than in normal subjects (Mann–Whitney U test, Z = −7.984, P < 0.001). Receiver operating characteristic curves (ROC) in patients with HCC versus those without HCC indicated the optimal cut-off value was 40.80 U/L for AFU, 10.86 μg/L for AFP and 1.92 pmol/L for TK1, respectively. The area under ROC curve (AUC) was 0.718 for AFU, 0.832 for AFP, 0.773 for TK1 and 0.900 for the combination of the three tumor markers. The combination resulted in a higher Youden index and a sensitivity of 85.3%. The combined detection of serum AFU, AFP and TK1 could play a complementary role in the diagnosis of HCC, and could significantly improve the sensitivity for the diagnosis of HCC. PMID:25870783

  11. [The clinical significance of PIVKA-II determination in patients with hepatocellular carcinoma: a comparative study with alpha-fetoprotein].

    PubMed

    Sakon, M; Monden, M; Goto, M; Kanai, T; Umeshita, K; Endo, W; Mori, T

    1990-05-01

    The changes in the plasma level of PIVKA-II (Protein Induced by Vitamin K Absence or Antagonist-II) following the treatment or progress of the disease was studied in 60 patients with hepatocellular carcinoma. The positivity rate determined by the changes in PIVKA-II was 58.4 percent (35/60 cases) and was about the same as those reported so far, all of which were obtained by a single determination of PIVKA-II. Plasma PIVKA-II was elevated in 61.9 percent (13/21 cases) of alpha-fetoprotein negative patients and it was almost identical with the overall positivity rate. In parallel with serum alpha-fetoprotein, the plasma level of PIVKA-II was decreased after the surgery or transcatheter arterial embolization and was increased when the recurrence or progress of the disease was observed. Furthermore, the nonspecific elevation of PIVKA-II due to the associated liver cirrhosis or chronic hepatitis was infrequent compared with that of alpha-fetoprotein. In 18 cases positive with both PIVKA-II and alpha-fetoprotein, a close correlation (R = 0.91) was observed between the changes of these markers during the progress or treatment of the disease. Thus, it was suggested that determination of PIVKA-II in blood might be useful not only in the diagnosis but in monitoring the progress or the effectiveness of treatments in hepatocellular carcinoma.

  12. Clinico-cytopathological spectrum of hepatocellular carcinoma, its correlation with serum alpha-fetoprotein level, and hepatitis B and C viral markers.

    PubMed

    Radhika, Nitin Shriniwas; Duseja, Ajay; Rajwanshi, Arwind; Gupta, Subhash Kumari; Sehgal, Shobha; Suri, Sudha; Chawla, Yogesh

    2004-01-01

    Fine-needle aspirationbiopsy (FNAB) is now widely accepted as a diagnostic modality for the treatment of hepatocellular carcinoma (HCC). The most common diagnostic problem in HCC is distinguishing it from a metastatic carcinoma. The literature from India on HCC is scanty. Hence, we studied the cytomorphological features of HCC and metastatic carcinoma. The study included 37 cases of space-occupying lesions (SOLs) of the liver as demonstrated by ultrasound or computed tomography (CT) scan. Cytomorphological features of these SOLs were analyzed in all subsequent to FNAB. Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody (anti-HCV) and alpha-fetoprotein (AFP) were determined in all the cases by enzyme-linked immunosorbent assay (ELISA). The cytopathological diagnosis was HCC in 22 and metastatic carcinoma of the liver in 15. The individual cytomorphological features and which helped to make a definite diagnosis of HCC were: a high nuclear cytoplasmic ratio (81.8%), predominantly trabecular pattern (63.6%) and atypical naked nuclei (100%). Other features were prominent multiple nucleoli (63.3%), hyperchromasia (100%) and moderate anisonucleosis (59%). AFP was elevated in 81.8% of the cases with a mean of 634.8+812.7 ng/ml. HBsAg by ELISA was found to be positive in 72.7% of cases while only 1 case (4.5%) was positive for anti-HCV. In 1 case (4.5%), there was dual infection due to hepatitis B virus (HBV) and HCV. No viral cause was found in 18.3% of cases. PMID:15682657

  13. SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein

    PubMed Central

    2013-01-01

    Objectives/background Ataxia with oculomotor apraxia defines a group of genetically distinct recessive ataxias including ataxia-telangectasia (A-T, ATM gene), ataxia with oculomotor apraxia type 1 (AOA1, APTX gene) and type 2 (AOA2, SETX gene). Although, a few unique clinical features differentiate each of these forms, the patients also share common clinical signs, such as the presence of cerebellar atrophy, sensorimotor axonal neuropathy, and elevated alpha-fetoprotein (AFP) serum level. Materials and methods We selected 22 Italian patients from 21 families, presenting progressive cerebellar ataxia, axonal neuropathy, and elevated serum AFP. We screened the coding regions of ATM, APTX and SETX genes for point mutations by direct sequencing or DHPLC, and searched genomic rearrangements in SETX by MLPA analysis. In selected cases, quantification of ATM and senataxin proteins was performed by Western blot. Clinical, neurophysiological, and neuroimaging data were collected. Results Thirteen patients (12 families) carried SETX mutations (AOA2, 57%), two were mutated in ATM (A-T), and three in APTX (AOA1). In three remaining patients, we could not find pathogenic mutations, and in one case we found, in homozygosis, the SETX p.K992R polymorphism (population frequency 1-2%). In AOA2 cases, we identified 14 novel and three reported SETX mutations. Signs at onset were gait ataxia and facial dyskinesia, and the age ranged between 11 and 18 years. None had obvious oculomotor apraxia at the latest examination (age 14–45 years). The patient carrying the p.K992R SETX polymorphism had a phenotype similar to that of the diagnosed AOA2 patients, while the other three undiagnosed subjects had a very late onset and a few distinguishing clinical features. Discussion and conclusions We describe a large series of 13 AOA2 Italian patients. The phenotype was consistent with previous descriptions of AOA2, except for a higher frequency of strabism, and for the absence of oculomotor

  14. Maternal serum alpha-fetoprotein levels in low birth weight singleton pregnancies.

    PubMed

    Buckland, C M; Thom, H; Campbell, A G

    1984-01-01

    Maternal serum alpha fetoprotein (MSAFP) measurement between 16 and 21 weeks gestation is used to define a group of women with an increased risk of fetal abnormality, particularly open neural tube defect. The test is strongly gestation dependent and women with high MSAFP levels require sonar scan examination to define gestation, exclude twins and examine the fetus for obvious malformation or death. It has been reported that women with no primary cause for raised MSAFP have an increased incidence of low birth weight babies. Conflicting reports have separately ascribed these to premature delivery and to intra-uterine growth retardation. We have studied the relationship between MSAFP and low birth weight infants with respect to both prematurity and retarded fetal growth. MSAFP values were expressed as multiples of the appropriate weekly median (MOM) values relating to normal pregnancies with normal outcomes at term. For our normal population an MSAFP value of 2 MOM is the 95% centile, i.e. 5% of normal outcome pregnancies of sure gestation will have MSAFP values in the second trimester which are at or above 2 MOM. Information was available on 389 women whose infants were liveborn singletons weighing 2.5 kg or less. 33 (8.5%) of these women had MSAFP greater than 2 MOM (p less than 0.005) and of the 145 women whose babies weighed less than 2 kg, 17 (11.7%) had MSAFP at this level (p less than 0.001) Tab. I).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Regulation of the alpha-fetoprotein promoter: Ku binding and DNA spatial conformation.

    PubMed

    Liénard, P; De Mees, C; Drèze, P-L; Dieu, M; Dierick, J-F; Raes, M; Szpirer, J; Szpirer, C

    2006-10-01

    This work shows that the proximal promoter of the mouse Afp gene contains a Ku binding site and that Ku binding is associated with down-regulation of the transcriptional activity of the Afp promoter. The Ku binding site is located in a segment able to adopt a peculiar structured form, probably a hairpin structure. Interestingly, the structured form eliminates the binding sites of the positive transcription factor HNF1. Furthermore, a DNAse hypersensitive site is detected in footprinting experiments done with extracts of AFP non-expressing hepatoma cells. These observations suggest that the structured form is stabilised by Ku and is associated with extinction of the gene in AFP non-expressing hepatic cells.

  16. Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation

    PubMed Central

    Matsumoto, Kohei; Ueyama, Hiroya; Matsumoto, Kenshi; Akazawa, Yoichi; Komori, Hiroyuki; Takeda, Tsutomu; Murakami, Takashi; Asaoka, Daisuke; Hojo, Mariko; Tomita, Natsumi; Nagahara, Akihito; Kajiyama, Yoshiaki; Yao, Takashi; Watanabe, Sumio

    2016-01-01

    AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation (GCED). METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer (CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital. GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate. RESULTS Six cases (5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases (139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC (66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED (positivity, 83.3%), immunohistochemically. CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological

  17. Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation

    PubMed Central

    Matsumoto, Kohei; Ueyama, Hiroya; Matsumoto, Kenshi; Akazawa, Yoichi; Komori, Hiroyuki; Takeda, Tsutomu; Murakami, Takashi; Asaoka, Daisuke; Hojo, Mariko; Tomita, Natsumi; Nagahara, Akihito; Kajiyama, Yoshiaki; Yao, Takashi; Watanabe, Sumio

    2016-01-01

    AIM To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation (GCED). METHODS We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer (CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital. GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate. RESULTS Six cases (5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases (139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC (66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED (positivity, 83.3%), immunohistochemically. CONCLUSION Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological

  18. [Alpha fetoprotein and neonatal jaundice. Contribution to the study of a physiopathologic mechanism].

    PubMed

    Tourne, C E; Brettes, J P; Guez, G; Ritter, J; Gandar, R

    1977-01-01

    The increase in the maternal plasma A.F.P. level is due to an hypoxia of the foetus. The prospective study of 851 single pregnancies shows that there is a significant rise in the A.F.P. levels during the last days of the pregnancy if the babies are going to exhibit a so-called physiological jaundice at birth: the decrease of the A.F.P. levels in these cases is four times slower than in normal cases. The prospective study of another group of 404 pregnancies gave the same results for the A.F.P. level of the blood of the umbilical cord. Statistical analysis showed that the pathological conditions capable of increasing the A.F.P. levels are related to neo-natal jaundice. The neo-natal jaundice may be due to a factor of foetal hypoxia capable of inducing an over stimulation of the foetal erythropoiesis. The results of this mechanism would be a quantitative disequilibrium between an increased hemolysis and a reduced bilirubine fixation capacity during the neo-natal period.

  19. Sugar chain of alpha-fetoprotein produced in human yolk sac tumor.

    PubMed

    Yamashita, K; Hitoi, A; Tsuchida, Y; Nishi, S; Kobata, A

    1983-10-01

    The carbohydrate moiety of alpha-fetoprotein purified from human yolk sac tumors grown in nude mice was quantitatively released from the polypeptide chain as oligosaccharides by hydrazinolysis. The oligosaccharides were separated into a neutral and two acidic oligosaccharides by paper electrophoresis. By sequential exoglycosidase digestion in combination with per-O-methylation study and periodate oxidation, their structures were determined to be: Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(GlcNAc beta 1 leads to 4) (Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAcOT, Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(GlcNAc beta 1 leads to 4) (Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAcOT; and Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 6(GlcNAc beta 1 leads to 4) (Sia alpha 2 leads to 6Gal beta 1 leads to 4GlcNAc beta 1 leads to 2Man alpha 1 leads to 3)Man beta 1 leads to 4 GlcNAc beta 1 leads to 4(Fuc alpha 1 leads to 6)GlcNAcOT, in which Gal is galactose, GlcNac is N-acetylglucosamine, Man is mannose, Fuc is fucose, Sia is sialic acid, and Subscript OT is the NaB3H4-reduced oligosaccharide. PMID:6192908

  20. Expression of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein in normal salivary glands and primary salivary gland tumors.

    PubMed

    Günhan, O; Evren, G; Demiriz, M; Can, C; Celasun, B; Finci, R

    1992-12-01

    The distribution of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein was studied in 38 primary salivary gland tumors. S-100 protein, a useful marker of myoepithelial cells, was demonstrated in some benign tumors. Carcinoembryonic antigen expression was consistently positive in adenoid cystic carcinoma. Demonstration of epithelial membrane antigen helped to confirm the epithelial nature of some neoplastic cells. Alpha fetoprotein was not expressed in any of the cases examined. No correlation was found between immunopositivity and tumor behavior in the present series.

  1. Artificial antigen-presenting cells expressing AFP158-166 peptide and interleukin-15 activate AFP-specific cytotoxic T lymphocytes

    PubMed Central

    Sun, Longhao; Guo, Hao; Jiang, Ruoyu; Lu, Li; Liu, Tong; Zhang, Zhixiang; He, Xianghui

    2016-01-01

    Professional antigen-presenting cells (APCs) are potent generators of tumor antigen-specific cytotoxic T lymphocytes (CTLs) for adoptive immunotherapy; however, generation of APCs is cumbersome, expensive, and subject to the tumor microenvironment. Artificial APCs (aAPCs) have been developed as a cost-effective alternative to APCs. We developed a cellular aAPC that efficiently generated alpha-fetoprotein (AFP)-specific CTLs. We genetically modified the human B cell lymphoma cell line BJAB with a lentiviral vector to establish an aAPC called BA15. The expression of AFP158-166-HLA-A*02:01 complex, CD80, CD86, and interleukin (IL)-15 in BA15 cells was assessed. The efficiency of BA15 at generating AFP-specific CTLs and the specific cytotoxicity of CTLs against AFP+ cells were also determined. BA15 cells expressed high levels of AFP158-166 peptide, HLA-A2, CD80, CD86, and IL-15. BA15 cells also exhibited higher efficiency in generating AFP-specific CTLs than did dendritic cells. These CTLs had greater cytotoxicity against AFP+ hepatocellular carcinoma cells than did CTLs obtained from dendritic cells in vitro and in vivo. Our novel aAPC system could provide a robust platform for the generation of functional AFP-specific CTLs for adoptive immunotherapy of hepatocellular carcinoma. PMID:27007051

  2. In vitro differentiation and maturation of mouse embryonic stem cells into hepatocytes

    SciTech Connect

    Ishii, Takamichi; Yasuchika, Kentaro; Fujii, Hideaki; Hoppo, Toshitaka; Baba, Shinji; Naito, Masato; Machimoto, Takafumi; Kamo, Naoko; Suemori, Hirofumi; Nakatsuji, Norio; Ikai, Iwao . E-mail: ikai@kuhp.kyoto-u.ac.jp

    2005-09-10

    It is difficult to induce the maturation of embryonic stem (ES) cells into hepatocytes in vitro. We previously reported that Thy1-positive mesenchymal cells derived from the mouse fetal liver promote the maturation of hepatic progenitor cells. Here, we isolated alpha-fetoprotein (AFP)-producing cells from mouse ES cells for subsequent differentiation into hepatocytes in vitro by coculture with Thy1-positive cells. ES cells expressing green fluorescent protein (GFP) under the control of an AFP promoter were cultured under serum- and feeder layer-free culture conditions. The proportion of GFP-positive cells plateaued at 41.6 {+-} 12.2% (means {+-} SD) by day 7. GFP-positive cells, isolated by flow cytometry, were cultured in the presence or absence of Thy1-positive cells as a feeder layer. Isolated GFP-positive cells were stained for AFP, Foxa2, and albumin. The expression of mRNAs encoding tyrosine amino transferase, tryptophan 2,3-dioxygenase, and glucose-6-phosphatase were only detected following coculture with Thy1-positive cells. Following coculture with Thy1-positive cells, the isolated cells produced and stored glycogen. Ammonia clearance activity was also enhanced following coculture. Electron microscopic analysis indicated that the cocultured cells exhibited the morphologic features of mature hepatocytes. In conclusion, coculture with Thy1-positive cells in vitro induced the maturation of AFP-producing cells isolated from ES cell cultures into hepatocytes.

  3. CRB2 Mutations Produce a Phenotype Resembling Congenital Nephrosis, Finnish Type, with Cerebral Ventriculomegaly and Raised Alpha-Fetoprotein

    PubMed Central

    Slavotinek, Anne; Kaylor, Julie; Pierce, Heather; Cahr, Michelle; DeWard, Stephanie J.; Schneidman-Duhovny, Dina; Alsadah, Adnan; Salem, Fadi; Schmajuk, Gabriela; Mehta, Lakshmi

    2015-01-01

    We report five fetuses and a child from three families who shared a phenotype comprising cerebral ventriculomegaly and echogenic kidneys with histopathological findings of congenital nephrosis. The presenting features were greatly elevated maternal serum alpha-fetoprotein (MSAFP) or amniotic fluid alpha-fetoprotein (AFAFP) levels or abnormalities visualized on ultrasound scan during the second trimester of pregnancy. Exome sequencing revealed deleterious sequence variants in Crumbs, Drosophila, Homolog of, 2 (CRB2) consistent with autosomal-recessive inheritance. Two fetuses with cerebral ventriculomegaly and renal microcysts were compound heterozygotes for p.Asn800Lys and p.Trp759Ter, one fetus with renal microcysts was a compound heterozygote for p.Glu643Ala and p.Asn800Lys, and one child with cerebral ventriculomegaly, periventricular heterotopias, echogenic kidneys, and renal failure was homozygous for p.Arg633Trp in CRB2. Examination of the kidneys in one fetus showed tubular cysts at the corticomedullary junction and diffuse effacement of the epithelial foot processes and microvillous transformation of the renal podocytes, findings that were similar to those reported in congenital nephrotic syndrome, Finnish type, that is caused by mutations in nephrin (NPHS1). Loss of function for crb2b and nphs1 in Danio rerio were previously shown to result in loss of the slit diaphragms of the podocytes, leading to the hypothesis that nephrosis develops from an inability to develop a functional glomerular barrier. We conclude that the phenotype associated with CRB2 mutations is pleiotropic and that the condition is an important consideration in the evaluation of high MSAFP/AFAFP where a renal cause is suspected. PMID:25557780

  4. CRB2 mutations produce a phenotype resembling congenital nephrosis, Finnish type, with cerebral ventriculomegaly and raised alpha-fetoprotein.

    PubMed

    Slavotinek, Anne; Kaylor, Julie; Pierce, Heather; Cahr, Michelle; DeWard, Stephanie J; Schneidman-Duhovny, Dina; Alsadah, Adnan; Salem, Fadi; Schmajuk, Gabriela; Mehta, Lakshmi

    2015-01-01

    We report five fetuses and a child from three families who shared a phenotype comprising cerebral ventriculomegaly and echogenic kidneys with histopathological findings of congenital nephrosis. The presenting features were greatly elevated maternal serum alpha-fetoprotein (MSAFP) or amniotic fluid alpha-fetoprotein (AFAFP) levels or abnormalities visualized on ultrasound scan during the second trimester of pregnancy. Exome sequencing revealed deleterious sequence variants in Crumbs, Drosophila, Homolog of, 2 (CRB2) consistent with autosomal-recessive inheritance. Two fetuses with cerebral ventriculomegaly and renal microcysts were compound heterozygotes for p.Asn800Lys and p.Trp759Ter, one fetus with renal microcysts was a compound heterozygote for p.Glu643Ala and p.Asn800Lys, and one child with cerebral ventriculomegaly, periventricular heterotopias, echogenic kidneys, and renal failure was homozygous for p.Arg633Trp in CRB2. Examination of the kidneys in one fetus showed tubular cysts at the corticomedullary junction and diffuse effacement of the epithelial foot processes and microvillous transformation of the renal podocytes, findings that were similar to those reported in congenital nephrotic syndrome, Finnish type, that is caused by mutations in nephrin (NPHS1). Loss of function for crb2b and nphs1 in Danio rerio were previously shown to result in loss of the slit diaphragms of the podocytes, leading to the hypothesis that nephrosis develops from an inability to develop a functional glomerular barrier. We conclude that the phenotype associated with CRB2 mutations is pleiotropic and that the condition is an important consideration in the evaluation of high MSAFP/AFAFP where a renal cause is suspected.

  5. Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3.

    PubMed

    Volk, Michael L; Hernandez, Jose C; Su, Grace L; Lok, Anna S; Marrero, Jorge A

    2007-01-01

    Current surveillance strategies for hepatocellular carcinoma (HCC) are applied uniformly in patients with cirrhosis, regardless of their cancer risk. The aim of this study was to compare the performance characteristics of the biomarkers alpha-fetoprotein (AFP), des-gamma carboxyprothrombin (DCP), and lectin-bound AFP (AFP-L3) in the diagnosis of HCC, and to determine the effect of risk factors for HCC on test performance. Eighty-four patients with HCC and 169 patients with cirrhosis were enrolled and their serum analyzed for total AFP, AFP-L3 and DCP. Receiver-operating characteristic (ROC) curves were constructed to determine the performance characteristics. DCP was significantly better than total AFP or AFP-L3 in differentiating HCC from cirrhosis, with a sensitivity of 86% and specificity of 93%. When subjects were divided into two groups by their risk for HCC, all 3 markers had a lower sensitivity and area under the ROC curve in the high-risk group compared to the low-risk group. In conclusion, DCP has the best performance characteristics of all 3 serum markers for the diagnosis of HCC. Serum biomarkers may be less sensitive and specific in the highest risk patients.

  6. Serum albumin and globulin analysis for hepatocellular carcinoma detection avoiding false-negative results from alpha-fetoprotein test negative subjects

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Feng, Shangyuan; Lin, Juqiang; Zeng, Yongyi; Li, Ling; Huang, Zufang; Li, Buhong; Zeng, Haishan; Chen, Rong

    2013-11-01

    Surface-enhanced Raman spectroscopy (SERS) of serum albumin and globulin were employed to detect hepatocellular carcinoma (HCC). Tentative assignments of SERS bands show specific biomolecular changes associated with cancer development. These changes include a decrease in relative amounts of tryptophan, glutamine, glycine, and serine, indicating excessive consumption of amino acids for protein duplication. Principal component analysis was also introduced to analyze the obtained spectra, resulting in both diagnostic sensitivity and specificity of 100%. More importantly, it reveals that this method can detect HCC patients with alpha-fetoprotein negative test results, suggesting its great potential as a new alternative to detect HCC.

  7. [Level of prolactin, gonadotrophin, testosterone, and alpha fetoprotein in serum of blood donors with antibodies to hepatitis c virus (anti-HCV)].

    PubMed

    Rzeszowska, G; Jagiełło-Wójtowicz, E; Krawczuk, G; Baran, E; Bielec, D; Fijałka-Rymar, M; Surmaczyńska, B

    1993-01-01

    The study was aimed at the determination of serum levels of the investigated hormones (prolactin, gonadotrophins, testosterone and alpha-fetoprotein) in blood donors with antibodies to hepatitis C virus. The observed group consisted of 50 men of age between 22 and 47 years. The blood serum concentrations of hormones were determined by RIA method using the ready made reagent kits. No characteristic changes were observed in the serum hormones levels except for prolactin. Mean value of serum prolactin concentration was higher in blood donors than those in the control group. PMID:7688903

  8. A sensitive label–free amperometric immunosensor for alpha-fetoprotein based on gold nanorods with different aspect ratio

    PubMed Central

    Zhou, Chunyang; Liu, Dali; Xu, Lin; Li, Qingling; Song, Jian; Xu, Sai; Xing, Ruiqing; Song, Hongwei

    2015-01-01

    A simple and accurate label–free amperometric immunosensor for α–fetoprotein (AFP) detection is developed based on gold nanorods (GNRs) with different aspect ratio and compared with gold particles (GNPs). The positively charged GNRs and GNPs due to the surface immobilized cetyltrimethyl ammonium bromide (CTAB) can adsorb the negatively charged AFP antibody (Ab) directly. The presence of the GNRs not only enhanced the immobilized amount of biomolecules, but also improved the electrochemical properties of the immunosensor. With the aid of GNRs, the electrochemical signal was greatly enhanced in comparison with GNPs. Under optimal conditions, the proposed immunosensor could detect AFP in a linear range from 0.1 to 200 ng/mL with a detection limit of 0.04 ng/mL (signal–to–noise ratio = 3), and it also possessed good reproducibility and storage stability. Moreover, the detection of AFP in five human serum samples also showed satisfactory accuracy. The proposed methodology was potentially attractive for clinical immunoassay. PMID:25909588

  9. A sensitive label-free amperometric immunosensor for alpha-fetoprotein based on gold nanorods with different aspect ratio.

    PubMed

    Zhou, Chunyang; Liu, Dali; Xu, Lin; Li, Qingling; Song, Jian; Xu, Sai; Xing, Ruiqing; Song, Hongwei

    2015-01-01

    A simple and accurate label-free amperometric immunosensor for α-fetoprotein (AFP) detection is developed based on gold nanorods (GNRs) with different aspect ratio and compared with gold particles (GNPs). The positively charged GNRs and GNPs due to the surface immobilized cetyltrimethyl ammonium bromide (CTAB) can adsorb the negatively charged AFP antibody (Ab) directly. The presence of the GNRs not only enhanced the immobilized amount of biomolecules, but also improved the electrochemical properties of the immunosensor. With the aid of GNRs, the electrochemical signal was greatly enhanced in comparison with GNPs. Under optimal conditions, the proposed immunosensor could detect AFP in a linear range from 0.1 to 200 ng/mL with a detection limit of 0.04 ng/mL (signal-to-noise ratio = 3), and it also possessed good reproducibility and storage stability. Moreover, the detection of AFP in five human serum samples also showed satisfactory accuracy. The proposed methodology was potentially attractive for clinical immunoassay. PMID:25909588

  10. A sensitive photoelectrochemical biosensor for AFP detection based on ZnO inverse opal electrodes with signal amplification of CdS-QDs.

    PubMed

    Xu, Ru; Jiang, Yandong; Xia, Lei; Zhang, Tianxiang; Xu, Lin; Zhang, Shuang; Liu, Dali; Song, Hongwei

    2015-12-15

    In this work, ZnO inverse opals structure (IOs) based photoelectrochemical (PEC) electrode was fabricated for alpha-fetoprotein (AFP) detection. Then, the uniform CdS quantum dots (QDs) were hydrothermally synthesized, which allowed the binding of AFP and glucose oxidase (GOD) on CdS QDs, forming the AFP-CdS-GOD composite. The competitive immunosensor of AFP and the AFP-CdS-GOD composite with anti-AFP antibodies (Ab) immobilized on FTO (fluorine-doped tin oxide) /ZnO IOs electrode was successfully applied to the detection of AFP. GOD could catalyze glucose to produce hydrogen peroxide (H2O2) acting as an electron donor to scavenge photogenerated holes in the valence band of CdS QDs, reducing the recombination of electrons and holes of CdS QDs. Also the effective energy level matching between the conduction bands of CdS QDs and ZnO widened the range of light absorption, allowing for electron injection from excited CdS QDs to ZnO upon visible light irradiation, which enhanced the photocurrent. The results show that the immunosensor of AFP possesses a large linear detection range of 0.1-500 ng/ml with a detection limit of 0.01 ng/ml. It also exhibits excellent anti-interference property and acceptable stability. This work provides a promising method for achieving excellent photoelectrochemical biosensor detection of other proteins. PMID:26164013

  11. A sensitive photoelectrochemical biosensor for AFP detection based on ZnO inverse opal electrodes with signal amplification of CdS-QDs.

    PubMed

    Xu, Ru; Jiang, Yandong; Xia, Lei; Zhang, Tianxiang; Xu, Lin; Zhang, Shuang; Liu, Dali; Song, Hongwei

    2015-12-15

    In this work, ZnO inverse opals structure (IOs) based photoelectrochemical (PEC) electrode was fabricated for alpha-fetoprotein (AFP) detection. Then, the uniform CdS quantum dots (QDs) were hydrothermally synthesized, which allowed the binding of AFP and glucose oxidase (GOD) on CdS QDs, forming the AFP-CdS-GOD composite. The competitive immunosensor of AFP and the AFP-CdS-GOD composite with anti-AFP antibodies (Ab) immobilized on FTO (fluorine-doped tin oxide) /ZnO IOs electrode was successfully applied to the detection of AFP. GOD could catalyze glucose to produce hydrogen peroxide (H2O2) acting as an electron donor to scavenge photogenerated holes in the valence band of CdS QDs, reducing the recombination of electrons and holes of CdS QDs. Also the effective energy level matching between the conduction bands of CdS QDs and ZnO widened the range of light absorption, allowing for electron injection from excited CdS QDs to ZnO upon visible light irradiation, which enhanced the photocurrent. The results show that the immunosensor of AFP possesses a large linear detection range of 0.1-500 ng/ml with a detection limit of 0.01 ng/ml. It also exhibits excellent anti-interference property and acceptable stability. This work provides a promising method for achieving excellent photoelectrochemical biosensor detection of other proteins.

  12. Solitary AFP- and PIVKA-II-producing hepatoid gastric cancer with giant lymph node metastasis.

    PubMed

    Iso, Yukihiro; Sawada, Tokihiko; Shimoda, Mitsugi; Rokkaku, Kyu; Ohkura, Yasuo; Kubota, Keiichi

    2005-01-01

    A 61-year-old man was admitted to our hospital because of abdominal pain and an abdominal mass. The patient had anemia and elevated serum alpha-fetoprotein (AFP) (9630ng/mL) and PIVKA-II (91mAU/mL) levels. Roentgenographic examination revealed an extra-gastric tumor in the upper abdomen, and gastroscopy revealed Bormann type 2 gastric cancer in the lower portion of the stomach. The preoperative diagnosis was synchronous gastric cancer and hepatocellular carcinoma (HCC), and surgery was performed. The extra-gastric tumor appeared to be an extra-hepatically growing HCC because the tumor was fed by vessels ramifying from the umbilical portion of the liver. Distal gastrectomy with resection of the extra-gastric tumor was performed, and histological examination of the resected specimen revealed that the gastric cancer was an AFP-producing hepatoid gastric adenocarcinoma and that the extra-gastric tumor was a lymph node metastasis. AFP-producing hepatoid gastric adenocarcinoma tends to metastasize to the regional lymph nodes and form a giant tumor. A giant tumor in the upper abdomen associated with gastric cancer may therefore be a clinical manifestation of AFP-producing hepatoid gastric adenocarcinoma.

  13. Amniotic fluid-AFP in Down syndrome and other chromosome abnormalities.

    PubMed

    Crandall, B F; Matsumoto, M; Perdue, S

    1988-05-01

    80.2 Per cent of 111 Down syndrome pregnancies had anmiotic fluid (AF) alpha fetoprotein (AFP) levels on or below the median and 10.8 per cent at or below 0.5 MoM compared with 41.9 and 1.4 per cent of controls. These differences were even more striking when the gestational age was less than 18 weeks compared with greater than or equal to 18 weeks. No such association was seen for other chromosome abnormalities including trisomy 18,45,X and mosaics, 47,XXY,47,XXX, and other structural abnormalities and triploidy, even when high levels due to defects such as omphalocele and cystic hygroma were excluded. All cases of trisomy 13 and 80 per cent with 47,XYY had AF-AFP levels above the median. Selection of cases for karyotyping by a low level of AF-AFP would clearly fail to detect aneuploidies other than Down syndrome and is not recommended. A possible weak association between low maternal serum (MS) and AF-AFPs in Down syndrome was most evident at less than 18 weeks, suggesting that MS screening between 16 and 18 weeks may be the most informative time. PMID:2456565

  14. Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

    PubMed Central

    Toraih, Eman A; Fawzy, Manal S; El-Falouji, Abdullah I; Hamed, Elham O; Nemr, Nader A; Hussein, Mohammad H; Fadeal, Noha M Abd El

    2016-01-01

    Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profiles of three pluripotency-associated genes, OCT4, NANOG and SOX2, G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand CXCL2, and alpha-fetoprotein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed for relative quantification of the six target genes using the Livak method. In silico network analysis was also executed to explore the pluripotency and tumorigenetic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG, CXCR4 and AFP were significantly upregulated in late clinical stage HCC patients. In contrast, SOX2 and CXCL2 were markedly overexpressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of the SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high expression with late HCC could contribute to the acquisition of stem cell–like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have potential application in HCC prognosis and treatment. PMID:27623812

  15. Second-trimester maternal serum alpha-fetoprotein and human chorionic gonadotrophin screening for Down's syndrome in Hong Kong.

    PubMed

    Lam, Y H; Ghosh, A; Tang, M H; Tang, L C; Lee, C P; Sin, S Y; Ho, P K

    1998-06-01

    Second-trimester maternal serum screening for fetal Down's syndrome is well established in many Western countries. Its usefulness and acceptability is unknown in the Asian countries. Between June 1994 and December 1996, we offered second-trimester serum AFP and hCG screening to pregnant women in Hong Kong who were less than 35 years old and without other risk factors for chromosome abnormalities. Each woman was assigned a risk of having a Down's syndrome term pregnancy by using a computer software program that took into account her age. weight, AFP and hCG MOMs. All those with a risk of one in 250 or greater were designated screen-positive, subject to the revision of gestation by ultrasound examination. 9,177 women with singleton pregnancies (93 per cent were Chinese) were screened. The uptake of screening was 75 per cent. 281 women (three per cent) were initially classified to be screen-positive. After revision of the gestation by ultrasound examination, 183 women (two per cent) were 'true' screen-positive and 164 (90 per cent) accepted the offer of amniocentesis. Eight of these pregnancies were affected by Down's syndrome and all the women elected pregnancy termination. The odds of being affected, given a positive screening result, were one in 23. Six Down's syndrome pregnancies were missed by screening programme. The detection rate was 57 per cent. The study showed that second-trimester serum screening for fetal Down's syndrome was feasible and accepted in the Hong Kong population.

  16. Peri-Transplant Change in AFP Level: a Useful Predictor of Hepatocellular Carcinoma Recurrence Following Liver Transplantation.

    PubMed

    Yoo, Tae; Lee, Kwang-Woong; Yi, Nam-Joon; Choi, Young Rok; Kim, Hyeyoung; Suh, Suk-Won; Jeong, Jae Hong; Lee, Jeong-Moo; Suh, Kyung-Suk

    2016-07-01

    Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization. PMID:27366001

  17. A cyclized peptide derived from alpha fetoprotein inhibits the proliferation of ER-positive canine mammary cancer cells.

    PubMed

    Torres, Cristian Gabriel; Pino, Ana María; Sierralta, Walter Daniel

    2009-06-01

    The effects of estradiol (E2) and of an AFP-derived cyclized peptide (cP) on the proliferation of primary cultures of cancer cells isolated from spontaneous canine mammary tumors were studied. The cellular response to E2 and cP was related to the expression of estradiol receptor (isoforms alpha and beta). In ER-positive cells, 2 nM estradiol increased cell proliferation and the phosphorylation of ERK1/2; 2 microg/ml cP inhibited all these effects. Estradiol also increased HER2 immunoreactivity in ER-positive cells, an effect that was reverted to its basal values by cP. Estradiol stimulated in these cells the release of MMP2 and MMP9 and the shedding of HB-EGF, effects that the cP did not affect. ER-negative cells were refractory to estradiol or cP. All canine mammary tumor cells in culture responded to treatments analogously to human mammary cancer cells. Our results support the proposal of cP as a new, potentially effective therapeutic agent for the management of mammary cancer. PMID:19424616

  18. Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells.

    PubMed

    Chou, Song; Lodish, Harvey F

    2010-04-27

    Previously we showed that the ~2% of fetal liver cells reactive with an anti-CD3epsilon monoclonal antibody support ex vivo expansion of both fetal liver and bone marrow hematopoietic stem cells (HSCs); these cells express two proteins important for HSC ex vivo expansion, IGF2, and angiopoietin-like 3. Here we show that these cells do not express any CD3 protein and are not T cells; rather, we purified these HSC-supportive stromal cells based on the surface phenotype of SCF(+)DLK(+). Competitive repopulating experiments show that SCF(+)DLK(+) cells support the maintenance of HSCs in ex vivo culture. These are the principal fetal liver cells that express not only angiopoietin-like 3 and IGF2, but also SCF and thrombopoietin, two other growth factors important for HSC expansion. They are also the principal fetal liver cells that express CXCL12, a factor required for HSC homing, and also alpha-fetoprotein (AFP), indicating that they are fetal hepatic stem or progenitor cells. Immunocytochemistry shows that >93% of the SCF(+) cells express DLK and Angptl3, and a portion of SCF(+) cells also expresses CXCL12. Thus SCF(+)DLK(+) cells are a highly homogenous population that express a complete set of factors for HSC expansion and are likely the primary stromal cells that support HSC expansion in the fetal liver.

  19. Correlation between hepatitis B virus surface antigen level and alpha-fetoprotein in patients free of hepatocellular carcinoma or severe hepatitis.

    PubMed

    Akuta, Norio; Suzuki, Fumitaka; Kobayashi, Mariko; Hara, Tasuku; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Saitoh, Satoshi; Ikeda, Kenji; Kumada, Hiromitsu

    2014-01-01

    Alfa-fetoprotein (AFP) is used as a marker of early hepatocarcinogenesis. However, the impact of hepatitis B virus surface antigen (HBsAg) on this relationship in patients with HBV infection is not clear. The present study evaluated the relation between HBsAg and AFP levels at the initial visit in 1,610 untreated HBV patients, free of hepatocellular carcinoma (HCC) or severe hepatitis. The cumulative rate of HCC was significantly lower in patients with a low AFP level (≤10 µg/L; below the upper limit of normal) than in those with a high AFP level (≥11 µg/L) at the initial visit. In patients with HBsAg levels more than 500 IU/ml, HBsAg levels correlated significantly and negatively with AFP levels, and significantly with platelet count. Multivariate analysis of data of patients with HBsAg more than 500 IU/ml identified HBsAg (<7,000 IU/ml), albumin (<3.9 g/dl), platelet count (<20.0 × 10(4) /mm(3)), gamma-glutamyl transpeptidase (≥50 IU/L), aspartate aminotransferase (≥34 IU/L), HBeAg (positive), and HBV core-related antigen (≥3.0 log U/ml) as determinants of a high AFP. Especially, in patients with HBsAg more than 500 IU/ml and low transaminase levels (below the upper limit of normal), HBsAg was identified as significant determinant of a high AFP. On the other hand, in patients with HBsAg less than 500 IU/ml, multivariate analysis identified albumin, gamma-glutamyl transpeptidase, and HBV core-related antigen as determinants of a high AFP. The results indicated that HBsAg level seems to affect, at least in part, the AFP levels, and that it can be used as a surrogate marker of early hepatocarcinogenesis.

  20. Characteristics of three-dimensional prospectively isolated mouse bone marrow mesenchymal stem/stromal cell aggregates on nanoculture plates.

    PubMed

    Obara, Chizuka; Tomiyama, Ken-Ichi; Takizawa, Kazuya; Islam, Rafiqul; Yasuda, Takeshi; Gotoh, Takaya; Tajima, Katsushi

    2016-10-01

    Three-dimensional (3-D) aggregate culturing is useful for investigating the functional properties of mesenchymal stem/stromal cells (MSCs). For 3-D MSC analysis, however, pre-expansion of MSCs with two-dimensional (2-D) monolayer culturing must first be performed, which might abolish their endogenous properties. To avoid the need for 2-D expansion, we used prospectively isolated mouse bone marrow (BM)-MSCs and examined the differences in the biological properties of 2-D and 3-D MSC cultures. The BM-MSCs self-assembled into aggregates on nanoculture plates (NCP) that have nanoimprinted patterns with a low-cellular binding texture. The 3-D MSCs proliferated at the same rate as 2-D-cultured cells by only diffusion culture and secreted higher levels of pro-angiogenic factors such as vascular endothelial growth factor and hepatocyte growth factor (HGF). Conditioned medium from 3-D MSC cultures promoted more capillary formation than that of 2-D MSCs in an in vitro tube formation assay. Matrigel-implanted 3-D MSC aggregates tended to induce angiogenesis in host mice. The 3-D culturing on NCP induced alpha-fetoprotein (AFP) expression in MSCs without the application of AFP- or endodermal-inducible factors, possibly via an HGF-autocrine mechanism, and maintained their differentiation ability for adipocytes, osteocytes, and chondrocytes. Prospectively isolated mouse BM-MSCs expressed low/negative stemness-related genes including Oct3/4, Nanog, and Sox2, which were not enhanced by NCP-based 3-D culturing, suggesting that some of these cells differentiate into meso-endodermal layer cells. Culturing of prospectively isolated MSCs on NCP in 3-D allows the analysis of the biological properties of more closely endogenous BM-MSCs and might contribute to tissue engineering and repair.

  1. Characteristics of three-dimensional prospectively isolated mouse bone marrow mesenchymal stem/stromal cell aggregates on nanoculture plates.

    PubMed

    Obara, Chizuka; Tomiyama, Ken-Ichi; Takizawa, Kazuya; Islam, Rafiqul; Yasuda, Takeshi; Gotoh, Takaya; Tajima, Katsushi

    2016-10-01

    Three-dimensional (3-D) aggregate culturing is useful for investigating the functional properties of mesenchymal stem/stromal cells (MSCs). For 3-D MSC analysis, however, pre-expansion of MSCs with two-dimensional (2-D) monolayer culturing must first be performed, which might abolish their endogenous properties. To avoid the need for 2-D expansion, we used prospectively isolated mouse bone marrow (BM)-MSCs and examined the differences in the biological properties of 2-D and 3-D MSC cultures. The BM-MSCs self-assembled into aggregates on nanoculture plates (NCP) that have nanoimprinted patterns with a low-cellular binding texture. The 3-D MSCs proliferated at the same rate as 2-D-cultured cells by only diffusion culture and secreted higher levels of pro-angiogenic factors such as vascular endothelial growth factor and hepatocyte growth factor (HGF). Conditioned medium from 3-D MSC cultures promoted more capillary formation than that of 2-D MSCs in an in vitro tube formation assay. Matrigel-implanted 3-D MSC aggregates tended to induce angiogenesis in host mice. The 3-D culturing on NCP induced alpha-fetoprotein (AFP) expression in MSCs without the application of AFP- or endodermal-inducible factors, possibly via an HGF-autocrine mechanism, and maintained their differentiation ability for adipocytes, osteocytes, and chondrocytes. Prospectively isolated mouse BM-MSCs expressed low/negative stemness-related genes including Oct3/4, Nanog, and Sox2, which were not enhanced by NCP-based 3-D culturing, suggesting that some of these cells differentiate into meso-endodermal layer cells. Culturing of prospectively isolated MSCs on NCP in 3-D allows the analysis of the biological properties of more closely endogenous BM-MSCs and might contribute to tissue engineering and repair. PMID:27100525

  2. Interrelationships among biological activity, disulfide bonds, secondary structure, and metal ion binding for a chemically synthesized 34-amino-acid peptide derived from alpha-fetoprotein.

    PubMed

    MacColl, R; Eisele, L E; Stack, R F; Hauer, C; Vakharia, D D; Benno, A; Kelly, W C; Mizejewski, G J

    2001-10-01

    A 34-amino-acid peptide has been chemically synthesized based on a sequence from human alpha-fetoprotein. The purified peptide is active in anti-growth assays when freshly prepared in pH 7.4 buffer at 0.20 g/l, but this peptide slowly becomes inactive. This functional change is proven by mass spectrometry to be triggered by the formation of an intrapeptide disulfide bond between the two cysteine residues on the peptide. Interpeptide cross-linking does not occur. The active and inactive forms of the peptide have almost identical secondary structures as shown by circular dichroism (CD). Zinc ions bind to the active peptide and completely prevents formation of the inactive form. Cobalt(II) ions also bind to the peptide, and the UV-Vis absorption spectrum of the cobalt-peptide complex shows that: (1) a near-UV sulfur-to-metal-ion charge-transfer band had a molar extinction coefficient consistent with two thiolate bonds to Co(II); (2) the lowest-energy visible d-d transition maximum at 659 nm, also, demonstrated that the two cysteine residues are ligands for the metal ion; (3) the d-d molar extinction coefficient showed that the metal ion-ligand complex was in a distorted tetrahedral symmetry. The peptide has two cysteines, and it is speculated that the other two metal ion ligands might be the two histidines. The Zn(II)- and Co(II)-peptide complexes had similar peptide conformations as indicated by their ultraviolet CD spectra, which differed very slightly from that of the free peptide. Surprisingly, the cobalt ions acted in the reverse of the zinc ions in that, instead of stabilizing anti-growth form of the peptide, they catalyzed its loss. Metal ion control of peptide function is a saliently interesting concept. Calcium ions, in the conditions studied, apparently do not bind to the peptide. Trifluoroethanol and temperature (60 degrees C) affected the secondary structure of the peptide, and the peptide was found capable of assuming various conformations in solution

  3. Effects of extracellular matrixes and growth factors on the hepatic differentiation of human embryonic stem cells.

    PubMed

    Ishii, Takamichi; Fukumitsu, Ken; Yasuchika, Kentaro; Adachi, Keiko; Kawase, Eihachiro; Suemori, Hirofumi; Nakatsuji, Norio; Ikai, Iwao; Uemoto, Shinji

    2008-08-01

    Hepatocytes derived from human embryonic stem cells (hESCs) are a potential cell source for regenerative medicine. However, the definitive factors that are responsible for hepatic differentiation of hESCs remain unclear. We aimed to evaluate the effects of various extracellular matrixes and growth factors on endodermal differentiation and to optimize the culture conditions to induce hepatic differentiation of hESCs. The transgene vector that contained enhanced green fluorescent protein (EGFP) under the control of human alpha-fetoprotein (AFP) enhancer/promoter was transfected into hESC lines. The transgenic hESCs were cultured on extracellular matrixes (collagen type I, laminin, and Matrigel) in the presence or absence of growth factors including hepatocyte growth factor (HGF), bone morphogenetic protein 4, fibroblast growth factor 4, all-trans-retinoic acid, and activin A. The expression of AFP-EGFP was measured by flow cytometry. The culture on Matrigel-coated dishes with 100 ng/ml activin A showed 19.5% of EGFP-positive proportions. Moreover, the sequential addition of 100 ng/ml activin A and 20 ng/ml HGF resulted in 21.7% and produced a higher yield of EGFP-positive cells than the group stimulated by activin A alone. RT-PCR and immunocytochemical staining revealed these EGFP-positive cells to differentiate into mesendoderm-like cells by use of activin A and then into hepatic endoderm cells by use of HGF. Two other hESC lines also differentiated into endoderm on the hepatic lineage by our method. In conclusion, we therefore found this protocol to effectively differentiate multiple hESC lines to early hepatocytes using activin A and HGF on Matrigel.

  4. High-performance fluorescence-encoded magnetic microbeads as microfluidic protein chip supports for AFP detection.

    PubMed

    Gong, Xiaoqun; Yan, Huan; Yang, Jiumin; Wu, Yudong; Zhang, Jian; Yao, Yingyi; Liu, Ping; Wang, Huiquan; Hu, Zhidong; Chang, Jin

    2016-10-01

    Fluorescence-encoded magnetic microbeads (FEMMs), with the fluorescence encoding ability of quantum dots (QDs) and magnetic enrichment and separation functions of Fe3O4 nanoparticles, have been widely used for multiple biomolecular detection as microfluidic protein chip supports. However, the preparation of FEMMs with long-term fluorescent encoding and immunodetection stability is still a challenge. In this work, we designed a novel high-temperature chemical swelling strategy. The QDs and Fe3O4 nanoparticles were effectively packaged into microbeads via the thermal motion of the polymer chains and the hydrophobic interaction between the nanoparticles and microbeads. The FEMMs obtained a highly uniform fluorescent property and long-term encoding and immunodetection stability and could be quickly magnetically separated and enriched. Then, the QD-encoded magnetic microbeads were applied to alpha fetoprotein (AFP) detection via sandwich immunoreaction. The properties of the encoded microspheres were characterized using a self-designed detecting apparatus, and the target molecular concentration in the sample was also quantified. The results suggested that the high-performance FEMMs have great potential in the field of biomolecular detection.

  5. High-performance fluorescence-encoded magnetic microbeads as microfluidic protein chip supports for AFP detection.

    PubMed

    Gong, Xiaoqun; Yan, Huan; Yang, Jiumin; Wu, Yudong; Zhang, Jian; Yao, Yingyi; Liu, Ping; Wang, Huiquan; Hu, Zhidong; Chang, Jin

    2016-10-01

    Fluorescence-encoded magnetic microbeads (FEMMs), with the fluorescence encoding ability of quantum dots (QDs) and magnetic enrichment and separation functions of Fe3O4 nanoparticles, have been widely used for multiple biomolecular detection as microfluidic protein chip supports. However, the preparation of FEMMs with long-term fluorescent encoding and immunodetection stability is still a challenge. In this work, we designed a novel high-temperature chemical swelling strategy. The QDs and Fe3O4 nanoparticles were effectively packaged into microbeads via the thermal motion of the polymer chains and the hydrophobic interaction between the nanoparticles and microbeads. The FEMMs obtained a highly uniform fluorescent property and long-term encoding and immunodetection stability and could be quickly magnetically separated and enriched. Then, the QD-encoded magnetic microbeads were applied to alpha fetoprotein (AFP) detection via sandwich immunoreaction. The properties of the encoded microspheres were characterized using a self-designed detecting apparatus, and the target molecular concentration in the sample was also quantified. The results suggested that the high-performance FEMMs have great potential in the field of biomolecular detection. PMID:27639146

  6. [Evaluation of trisomy 21 risk by serial determination of chorionic gonadotrophin hormone and alpha-fetoprotein: results of a national pilot study].

    PubMed

    Aymé, S; Aurran, Y; Chabal, F; Gombert, A; Loundou, H; Montfort, C; Sollier, M; Silvestri, A

    1993-02-01

    Previous studies, as early as 1984, have demonstrated the efficiency of maternal serum markers to screen for Down syndrome. These markers were AFP, hCG, oestriol and beta-1-glycoprotein. A pilot study was initiated in France in 1990 to evaluate these markers. It lasted from May 1990 until April 1991. 22,410 pregnancies were monitored in total, and 19,407 for women between 30 and 37 years of age. The pregnancy outcome was known for 20,151 cases (86.6%). Sensitivity and predictive value of the test was calculated on 17,362 dosages which outcome was known. The sensitivity based on hCG only was 59.4% (38/64) for trisomy 21 and positive predictive value 1.65% (38/2,307). This test is a better marker than maternal age. In the pilot study it induced a 13.2% rate of amniocentesis. If the risk was calculated using both hCG and AFP results, the performances of the test were better. At equal rate of amniocentesis, the double test increases the sensitivity (+9.5% at risk 1/200, +7% at risk 1/250, +14.4% at risk (1/350). The strategy of double dosages decreases the number of amniocentesis for a given sensitivity rate. This decrease is more spectacular for high levels of sensitivity. This pilot study confirms already published results. Maternal serum markers are the best tools, combined with maternal age to evaluate the risk of trisomy 21. PMID:7524931

  7. Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways

    PubMed Central

    Bortel, Nicola; Armeanu-Ebinger, Sorin; Schmid, Evi; Kirchner, Bettina; Frank, Jan; Kocher, Alexa; Schiborr, Christina; Warmann, Steven; Fuchs, Jörg; Ellerkamp, Verena

    2015-01-01

    In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC. PMID:26515460

  8. Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways.

    PubMed

    Bortel, Nicola; Armeanu-Ebinger, Sorin; Schmid, Evi; Kirchner, Bettina; Frank, Jan; Kocher, Alexa; Schiborr, Christina; Warmann, Steven; Fuchs, Jörg; Ellerkamp, Verena

    2015-12-01

    In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC.

  9. Clinical utility of simultaneous measurement of alpha-fetoprotein and des-γ-carboxy prothrombin for diagnosis of patients with hepatocellular carcinoma in China: A multi-center case-controlled study of 1,153 subjects.

    PubMed

    Song, Peipei; Feng, Xiaobin; Inagaki, Yoshinori; Song, Tianqiang; Zhang, Keming; Wang, Zhigang; Zheng, Shuguo; Ma, Kuansheng; Li, Qiang; Kong, Dalu; Wu, Qiang; Zhang, Ti; Zhao, Xin; Hasegawa, Kiyoshi; Sugawara, Yasuhiko; Kokudo, Norihiro; Tang, Wei

    2014-10-01

    This study aimed to investigate the clinical utility of simultaneous measurement of alphafetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) for hepatocellular carcinoma (HCC) diagnosis in Chinese patients predominantly caused by hepatitis B virus infection by a multi-center case-controlled study. Subjects were 1,153 individuals from three major hospitals in China, including 550 cases in HCC group, 164 in Malignant disease group, 182 in Benign disease group, 85 in Chronic liver disease group, and 173 in Normal group. Serum levels of AFP and DCP were measured and clinicopathological features were determined for all subjects. Results showed that the levels of DCP and AFP were significantly higher in HCC group (550 patients, 74.18% with HBV infection) than that in other four groups (P < 0.001). Receiver operating curves (ROC) indicated the optimal cut-off value was 86 mAU/mL for DCP with a sensitivity of 71.50% and specificity of 86.30%, and 21 ng/mL for AFP with a sensitivity of 68.00% and specificity of 93.20%. The area under ROC curve was 0.846 for DCP, 0.832 for AFP, and 0.890 for the combination of DCP and AFP. The combination of DCP and AFP resulted in a higher Youden index and a sensitivity of approximately 90%, even for small tumors. The simultaneous measurement of AFP and DCP could achieve a better sensitivity in diagnosing Chinese HCC patients, even for small tumors. PMID:25382443

  10. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

    PubMed Central

    Freyer, Nora; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Schrade, Petra; Bachmann, Sebastian; Damm, Georg; Seehofer, Daniel; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

    2016-01-01

    Abstract The hepatic differentiation of human induced pluripotent stem cells (hiPSC) holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D) hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D) cultures. A total of 100 × 106 hiPSC were seeded into each 3D bioreactor (n = 3). Differentiation into definitive endoderm (DE) was induced by adding activin A, Wnt3a, and sodium butyrate to the culture medium. For further maturation, hepatocyte growth factor and oncostatin M were added. The same differentiation protocol was applied to hiPSC maintained in 2D cultures. Secretion of alpha-fetoprotein (AFP), a marker for DE, was significantly (p < 0.05) higher in 2D cultures, while secretion of albumin, a typical characteristic for mature hepatocytes, was higher after hepatic differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple cytochrome P450 (CYP) isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in both groups, although at a lower level compared to primary human hepatocytes (PHH). CYP2B6 activities were significantly (p < 0.05) higher in 3D bioreactors compared with 2D cultures, which is in line with results from gene expression. Immunofluorescence staining showed that the majority of cells was positive for albumin, cytokeratin 18 (CK18), and hepatocyte nuclear factor 4-alpha (HNF4A) at the end of the differentiation process. In addition, cytokeratin 19 (CK19) staining revealed the formation of bile duct-like structures in 3D bioreactors similar to native liver tissue. The results indicate a better maturation of hiPSC in the 3D bioreactor system compared to 2D cultures and emphasize the potential of dynamic 3D culture

  11. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

    PubMed Central

    Freyer, Nora; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Schrade, Petra; Bachmann, Sebastian; Damm, Georg; Seehofer, Daniel; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

    2016-01-01

    Abstract The hepatic differentiation of human induced pluripotent stem cells (hiPSC) holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D) hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D) cultures. A total of 100 × 106 hiPSC were seeded into each 3D bioreactor (n = 3). Differentiation into definitive endoderm (DE) was induced by adding activin A, Wnt3a, and sodium butyrate to the culture medium. For further maturation, hepatocyte growth factor and oncostatin M were added. The same differentiation protocol was applied to hiPSC maintained in 2D cultures. Secretion of alpha-fetoprotein (AFP), a marker for DE, was significantly (p < 0.05) higher in 2D cultures, while secretion of albumin, a typical characteristic for mature hepatocytes, was higher after hepatic differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple cytochrome P450 (CYP) isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in both groups, although at a lower level compared to primary human hepatocytes (PHH). CYP2B6 activities were significantly (p < 0.05) higher in 3D bioreactors compared with 2D cultures, which is in line with results from gene expression. Immunofluorescence staining showed that the majority of cells was positive for albumin, cytokeratin 18 (CK18), and hepatocyte nuclear factor 4-alpha (HNF4A) at the end of the differentiation process. In addition, cytokeratin 19 (CK19) staining revealed the formation of bile duct-like structures in 3D bioreactors similar to native liver tissue. The results indicate a better maturation of hiPSC in the 3D bioreactor system compared to 2D cultures and emphasize the potential of dynamic 3D culture

  12. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor.

    PubMed

    Freyer, Nora; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Schrade, Petra; Bachmann, Sebastian; Damm, Georg; Seehofer, Daniel; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

    2016-01-01

    The hepatic differentiation of human induced pluripotent stem cells (hiPSC) holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D) hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D) cultures. A total of 100 × 10(6) hiPSC were seeded into each 3D bioreactor (n = 3). Differentiation into definitive endoderm (DE) was induced by adding activin A, Wnt3a, and sodium butyrate to the culture medium. For further maturation, hepatocyte growth factor and oncostatin M were added. The same differentiation protocol was applied to hiPSC maintained in 2D cultures. Secretion of alpha-fetoprotein (AFP), a marker for DE, was significantly (p < 0.05) higher in 2D cultures, while secretion of albumin, a typical characteristic for mature hepatocytes, was higher after hepatic differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple cytochrome P450 (CYP) isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in both groups, although at a lower level compared to primary human hepatocytes (PHH). CYP2B6 activities were significantly (p < 0.05) higher in 3D bioreactors compared with 2D cultures, which is in line with results from gene expression. Immunofluorescence staining showed that the majority of cells was positive for albumin, cytokeratin 18 (CK18), and hepatocyte nuclear factor 4-alpha (HNF4A) at the end of the differentiation process. In addition, cytokeratin 19 (CK19) staining revealed the formation of bile duct-like structures in 3D bioreactors similar to native liver tissue. The results indicate a better maturation of hiPSC in the 3D bioreactor system compared to 2D cultures and emphasize the potential of dynamic 3D culture systems

  13. Effects of a type I antifreeze protein (AFP) on the melting of frozen AFP and AFP+solute aqueous solutions studied by NMR microimaging experiment.

    PubMed

    Ba, Yong; Mao, Yougang; Galdino, Luiz; Günsen, Zorigoo

    2013-01-01

    The effects of a type I AFP on the bulk melting of frozen AFP solutions and frozen AFP+solute solutions were studied through an NMR microimaging experiment. The solutes studied include sodium chloride and glucose and the amino acids alanine, threonine, arginine, and aspartic acid. We found that the AFP is able to induce the bulk melting of the frozen AFP solutions at temperatures lower than 0 °C and can also keep the ice melted at higher temperatures in the AFP+solute solutions than those in the corresponding solute solutions. The latter shows that the ice phases were in super-heated states in the frozen AFP+solute solutions. We have tried to understand the first experimental phenomenon via the recent theoretical prediction that type I AFP can induce the local melting of ice upon adsorption to ice surfaces. The latter experimental phenomenon was explained with the hypothesis that the adsorption of AFP to ice surfaces introduces a less hydrophilic water-AFP-ice interfacial region, which repels the ionic/hydrophilic solutes. Thus, this interfacial region formed an intermediate chemical potential layer between the water phase and the ice phase, which prevented the transfer of water from the ice phase to the water phase. We have also attempted to understand the significance of the observed melting phenomena to the survival of organisms that express AFPs over cold winters. PMID:23860838

  14. Cloning and characterization of a novel Gladiolus hybridus AFP family gene (GhAFP-like) related to corm dormancy.

    PubMed

    Wu, Jian; Seng, Shanshan; Carianopol, Carina; Sui, Juanjuan; Yang, Qiuyan; Zhang, Fengqin; Jiang, Huiru; He, Junna; Yi, Mingfang

    2016-02-26

    Abscisic acid (ABA) is an important phytohormone controlling seed dormancy. AFPs (ABA INSENSITIVE FIVE BINDING PROTEINS) are reported to be negative regulators of the ABA signaling pathway. The involvement of AFPs in dormant vegetative organs remains poorly understood. Here, we isolated and characterized a novel AFP family member from Gladiolus dormant cormels, GhAFP-like, containing three conserved domains of the AFP family. Quantitative PCR analysis revealed that GhAFP-like was expressed in dormant organs and its expression was down-regulated along with corm storage. GhAFP-like was verified to be a nuclear-localized protein. Overexpressing GhAFP-like in Arabidopsis thaliana not only showed weaker seed dormancy with insensitivity to ABA, but also changed the expression of some ABA related genes. In addition, a primary root elongation assay showed GhAFP-like may involve in auxin signaling response. The results in this study indicate that GhAFP-like acts as a negative regulator in ABA signaling and is related to dormancy. PMID:26826388

  15. The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms.

    PubMed

    Vriens, Kim; Cools, Tanne L; Harvey, Peta J; Craik, David J; Braem, Annabel; Vleugels, Jozef; De Coninck, Barbara; Cammue, Bruno P A; Thevissen, Karin

    2016-01-01

    The radish defensin RsAFP2 was previously characterized as a peptide with potent antifungal activity against several plant pathogenic fungi and human pathogens, including Candida albicans. RsAFP2 induces apoptosis and impairs the yeast-to-hypha transition in C. albicans. As the yeast-to-hypha transition is considered important for progression to mature biofilms, we analyzed the potential antibiofilm activity of recombinant (r)RsAFP2, heterologously expressed in Pichia pastoris, against C. albicans biofilms. We found that rRsAFP2 prevents C. albicans biofilm formation with a BIC-2 (i.e., the minimal rRsAFP2 concentration that inhibits biofilm formation by 50% as compared to control treatment) of 1.65 ± 0.40 mg/mL. Moreover, biofilm-specific synergistic effects were observed between rRsAFP2 doses as low as 2.5 μg/mL to 10 μg/mL and the antimycotics caspofungin and amphotericin B, pointing to the potential of RsAFP2 as a novel antibiofilm compound. In addition, we characterized the solution structure of rRsAFP2 and compared it to that of RsAFP1, another defensin present in radish seeds. These peptides have similar amino acid sequences, except for two amino acids, but rRsAFP2 is more potent than RsAFP1 against planktonic and biofilm cultures. Interestingly, as in case of rRsAFP2, also RsAFP1 acts synergistically with caspofungin against C. albicans biofilms in a comparable low dose range as rRsAFP2. A structural comparison of both defensins via NMR analysis revealed that also rRsAFP2 adopts the typical cysteine-stabilized αβ-motif of plant defensins, however, no structural differences were found between these peptides that might result in their differential antifungal/antibiofilm potency. This further suggests that the conserved structure of RsAFP1 and rRsAFP2 bears the potential to synergize with antimycotics against C. albicans biofilms. PMID:26592804

  16. In situ hybridization of neuropeptide-encoding transcripts afp-1, afp-3, and afp-4 in neurons of the nematode Ascaris suum.

    PubMed

    Nanda, Jennifer Cho; Stretton, Antony O W

    2010-03-15

    The gene transcripts encoding both the AF8 and AF2 neuropeptides of the nematode Ascaris suum have been identified, cloned, and sequenced. The AF8 transcript (afp-3) encodes five identical copies of AF8; each peptide-encoding region is flanked by the appropriate dibasic or monobasic cleavage processing sites. The AF2 transcript (afp-4) encodes three identical copies of AF2 along with the appropriate cleavage sites. In contrast, the afp-1 transcript (Edison et al. [1997] Peptides 18:929-935) encodes six different AF peptides (AF3, 4, 10, 13, 14, 20) which all share a -PGVLRFamide C-terminus but have different N-terminal sequences. By using in situ hybridization, gene transcript expression patterns of afp-1, afp-3, and afp-4 (As-flp-18, As-flp-6, and As-flp-14, respectively, in the naming convention proposed by Blaxter et al. [1997] Parasitol Today 13:416-417) were determined in the adult A. suum anterior nervous system. Each gene transcript can be localized to a different subset of neurons. These subsets of neurons are different from the subsets of Caenorhabditis elegans neurons that were shown to express identical or similar peptides by the use of promoter GFP constructs (Kim and Li [2004] J Comp Neurol 475:540-550). PMID:20058230

  17. Status of the ATLAS Forward Physics (AFP) project

    NASA Astrophysics Data System (ADS)

    Chytka, Ladislav; Atlas Collaboration

    2013-04-01

    The ATLAS Forward Physics (AFP) project plans to add a set of detectors - silicon 3D pixel tracking detectors and QUARTIC time of flight detectors - in the forward region of the ATLAS experiment at the LHC. The AFP detectors will be placed around 210 m from the interaction point and are meant to detect protons produced at small angles. The detectors are to be housed in the so called Hamburg beam pipe - a movable beam pipe allowing horizontal movement of the detectors. The AFP is currently under approval with possible installation in 2014/15.

  18. Anti-human AFP variant monoclonal antibody in radioimmunodetection of primary hepatocellular carcinoma

    PubMed Central

    Liu, Yang; Wu, Meng-Chao; Chen, Han; Zhang, Bai-He; Qian, Guang-Xiang; Pan, Wen-Zhou; Qiang, Mei-Yu

    1997-01-01

    AIM: To investigate the affinity of AFP-R-LCA monoclonal antibody (AFP-R-LCA McAb) for AFP-positive primary hepatocellular carcinoma (HCC) cells. METHODS: AFP-R-LCA McAb was labeled by 131I. Eleven cases of HCC with AFP positivity, 6 with AFP negativity, and 4 with hepatitis B-related cirrhosis were investigated by radioimmunodetection. RESULTS: The 131I-AFP-R-LCA McAb immunoreacted with 9 of the HCC AFP-positive cases (9/11), but with none of the 6 AFP negative HCC cases or of the 4 cirrhosis patients. 131I-AFP-R-LCA McAb at a small dose (7.4 × 107 Bq/300 μg) was associated with no side effects as determined by the liver function test, prothrombin time (Pt) test and thyroid gland function test (P > 0.05). Two cases of AFP-positive HCC were not imaged because of large tumor size (diameter > 10 cm) and higher AFP concentration in serum (20000 μg/L). CONCLUSION: AFP-R-LCA McAb has a strong and special affinity to AFP-positive HCC cells and may be useful as a carrier for radioimmunodetection and radioimmunotherapy. PMID:27053873

  19. Status of the AFP project in the ATLAS experiment

    NASA Astrophysics Data System (ADS)

    Taševský, Marek

    2015-04-01

    Status of the AFP project in the ATLAS experiment is summarized. The AFP system is composed of a tracker to detect intact, diffractively scattered protons, and of a time-of-flight detector serving to suppress background from pile-up interactions. The whole system, located around 210 m from the main ATLAS detector, is placed in Roman Pots which move detectors from and to the incident proton beams. A typical distance of the closest approach of the tracker to these beams is 2-3 mm. The main physics motivation lies in measuring diffractive processes in runs with not a very high amount of pile-up.

  20. Status of the AFP project in the ATLAS experiment

    SciTech Connect

    Taševský, Marek

    2015-04-10

    Status of the AFP project in the ATLAS experiment is summarized. The AFP system is composed of a tracker to detect intact, diffractively scattered protons, and of a time-of-flight detector serving to suppress background from pile-up interactions. The whole system, located around 210 m from the main ATLAS detector, is placed in Roman Pots which move detectors from and to the incident proton beams. A typical distance of the closest approach of the tracker to these beams is 2–3 mm. The main physics motivation lies in measuring diffractive processes in runs with not a very high amount of pile-up.

  1. A compact SEOP 3He neutron spin filter with AFP NMR

    NASA Astrophysics Data System (ADS)

    Ino, Takashi; Arimoto, Yasushi; Shimizu, Hirohiko M.; Sakaguchi, Yoshifumi; Sakai, Kenji; Kira, Hiroshi; Shinohara, Takenao; Oku, Takayuki; Suzuki, Jun-ichi; Kakurai, Kazuhisa; Chang, Lieh-Jeng

    2012-02-01

    We developed AFP NMR in an aluminum container for polarized noble gas nuclei. The radio frequency magnetic field inside the aluminum container was designed from computer simulations. The polarization loss by the AFP spin flip of 3He was measured to be as low as 3.8×10-4. With this technique, a compact in-situ polarizing 3He neutron spin filter with AFP NMR is demonstrated.

  2. Determination of the expression of fish antifreeze protein (AFP) in 7th generation transgenic mice tissues and serum.

    PubMed

    Bagis, Haydar; Tas, Arzu; Kankavi, Orhan

    2008-06-01

    In this study, the presence of antifreeze protein (AFP) gene expression through successive generations in transgenic mice carrying the chimeric gene construct of the coding sequence for the AFP protein from ocean pout was investigated. AFP transgenic hemizygote mice were used for AFP gene expression. AFP genome expressions in transgenic mice were analyzed by Western blotting, and tissue location of AFP protein was shown by immunohistochemical and immunofluorescence techniques. Seventh transgenic mice from the established founders demonstrated the expression of AFP in organs such as the skin, oviduct, lung, kidney and liver tissues and serum except for the heart. Our results demonstrate successful expression of AFP gene products in several tissues and serum of transgenic mice, the association of in vivo expressed AFP protein, for the first time. These results indicate that the coding sequence for the AFP protein gene (ocean pout type III AFP gene) could be integrated and stably transcribed and expressed in the 7th generation of transgenic mice. In conclusion transgenic mouse lines would be a good model for the cryostudy of AFP and for the determination of AFP roles in several organs and tissues.

  3. Evaluation of the Acute Flacid Paralysis (AFP) Surveillance System in Bikita District Masvingo Province 2010

    PubMed Central

    2014-01-01

    Background AFP is a rare syndrome and serves as a proxy for poliomyelitis. The main objective of AFP surveillance is to detect circulating wild polio virus and provide data for developing effective prevention and control strategies as well planning and decision making. Bikita district failed to detect a case for the past two years. Findings A total of 31 health workers from 14 health centres were interviewed. Health worker knowledge on AFP was low in Bikita. The system was acceptable, flexible, and representative but not stable and not sensitive since it missed1 AFP case. The system was not useful to the district since data collected was not locally used in anyway. The cost of running the system was high. The district had no adequate resources to run the system. Reasons for not reporting cases was that the mothers were not bringing children with AFP and ignorance of health workers on syndromes captured under AFP. Conclusion Health worker’s knowledge on AFP was low and all interviewed workers needed training surveillance. The system was found to be flexible but unacceptable. Reasons for failure to detect AFP cases could be, no cases reporting to the centres, lack of knowledge on health workers hence failure to recognise symptoms, high staff turnover. PMID:24742014

  4. The Antifungal Plant Defensin HsAFP1 from Heuchera sanguinea Induces Apoptosis in Candida albicans

    PubMed Central

    Aerts, An M.; Bammens, Leen; Govaert, Gilmer; Carmona-Gutierrez, Didac; Madeo, Frank; Cammue, Bruno P. A.; Thevissen, Karin

    2011-01-01

    Plant defensins are active against plant and human pathogenic fungi (such as Candida albicans) and baker's yeast. However, they are non-toxic to human cells, providing a possible source for treatment of fungal infections. In this study, we characterized the mode of action of the antifungal plant defensin HsAFP1 from coral bells by screening the Saccharomyces cerevisiae deletion mutant library for mutants with altered HsAFP1 sensitivity and verified the obtained genetic data by biochemical assays in S. cerevisiae and C. albicans. We identified 84 genes, which when deleted conferred at least fourfold hypersensitivity or resistance to HsAFP1. A considerable part of these genes were found to be implicated in mitochondrial functionality. In line, sodium azide, which blocks the respiratory electron transport chain, antagonized HsAFP1 antifungal activity, suggesting that a functional respiratory chain is indispensable for HsAFP1 antifungal action. Since mitochondria are the main source of cellular reactive oxygen species (ROS), we investigated the ROS-inducing nature of HsAFP1. We showed that HsAFP1 treatment of C. albicans resulted in ROS accumulation. As ROS accumulation is one of the phenotypic markers of apoptosis in yeast, we could further demonstrate that HsAFP1 induced apoptosis in C. albicans. These data provide novel mechanistic insights in the mode of action of a plant defensin. PMID:21993350

  5. STEM?!?!

    ERIC Educational Resources Information Center

    Merrill, Jen

    2012-01-01

    The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.

  6. [Differentiation of human amniotic fluid stem cells into cardiomyocytes through embryonic body formation].

    PubMed

    Wang, Han; Chen, Shuai; Cheng, Xiang; Dou, Zhongying; Wang, Huayan

    2008-09-01

    To isolate human amniotic fluid stem cells (hASCs) and induce hASCs into cardiomyocytes after forming the embryonic bodies. We cultivated hASCs isolated from the amniotic fluid continually for over 42 passages. The biological characteristics of hASCs were detected by immunocytochemistry, RT-PCR and flow cytometer, hASCs at 10-15th passage were suspension cultured to form embryonic bodies that were induced to cardiomyocytes. Fibroblastoid-type hASCs were obtained. Immunocytochemistry, RT-PCR and flow cytometry analysis demonstrated that hASCs were positive for some specific makers of the embryonic stem cell. hASCs could form embryonic bodies that were alkaline-phosphatase positive and expressed fgf5, zeta-globin and alpha-fetoprotein. The embryonic bodies could differentiate into cardiomyocytes showing alpha-actin positive and Tbx5, Nkx2.5, GATA4 and alpha-MHC positive. We conclued that hASCs obtained from human amniotic fluid could differentiate into cardiomyocytes through the formation of embryonic bodies. PMID:19160841

  7. [Differentiation of human amniotic fluid stem cells into cardiomyocytes through embryonic body formation].

    PubMed

    Wang, Han; Chen, Shuai; Cheng, Xiang; Dou, Zhongying; Wang, Huayan

    2008-09-01

    To isolate human amniotic fluid stem cells (hASCs) and induce hASCs into cardiomyocytes after forming the embryonic bodies. We cultivated hASCs isolated from the amniotic fluid continually for over 42 passages. The biological characteristics of hASCs were detected by immunocytochemistry, RT-PCR and flow cytometer, hASCs at 10-15th passage were suspension cultured to form embryonic bodies that were induced to cardiomyocytes. Fibroblastoid-type hASCs were obtained. Immunocytochemistry, RT-PCR and flow cytometry analysis demonstrated that hASCs were positive for some specific makers of the embryonic stem cell. hASCs could form embryonic bodies that were alkaline-phosphatase positive and expressed fgf5, zeta-globin and alpha-fetoprotein. The embryonic bodies could differentiate into cardiomyocytes showing alpha-actin positive and Tbx5, Nkx2.5, GATA4 and alpha-MHC positive. We conclued that hASCs obtained from human amniotic fluid could differentiate into cardiomyocytes through the formation of embryonic bodies.

  8. Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma

    PubMed Central

    Vongsuvanh, Roslyn; van der Poorten, David; Iseli, Tristan; Strasser, Simone I.; McCaughan, Geoffrey W.; George, Jacob

    2016-01-01

    Robust biomarkers for population-level hepatocellular carcinoma (HCC) surveillance are lacking. We compared serum midkine (MDK), dickkopf-1 (DKK1), osteopontin (OPN) and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD) and 86 healthy controls (HC). Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49) had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86) of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54%) of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior. Conclusion: AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC. PMID:27219517

  9. Salvage therapy in patients with germ cell tumors.

    PubMed

    Einhorn, Lawrence H

    2015-01-01

    Testicular cancer is the most curable metastatic solid tumor. Initial chemotherapy is evidence based with risk stratification into three prognostic categories: good, intermediate, and advanced disease. Guidelines for disease management following progression after initial cisplatin combination chemotherapy are less clear. Options include salvage surgery for patients with anatomically confined relapse, standard-dose cisplatin combination chemotherapy, or high-dose chemotherapy with carboplatin plus etoposide with peripheral blood stem cell transplantation. Proper interpretation of a presumed relapse can be complicated. Growing masses on imaging studies might reflect a growing teratoma. Persistent elevations of serum human chorionic gonadotropin (hCG) or alpha fetoprotein (AFP) are only an indication for salvage therapy if there is a definitive rise in the tumor marker. Elevated and rising serum hCG as the only evidence of recurrence can be because of cross reactivity with luteinizing hormone or usage of marijuana rather than progressive cancer. Elevated liver function tests can cause rising serum AFP. PMID:25993183

  10. Characterization of the novel antifungal protein PgAFP and the encoding gene of Penicillium chrysogenum.

    PubMed

    Rodríguez-Martín, Andrea; Acosta, Raquel; Liddell, Susan; Núñez, Félix; Benito, M José; Asensio, Miguel A

    2010-04-01

    The strain RP42C from Penicillium chrysogenum produces a small protein PgAFP that inhibits the growth of some toxigenic molds. The molecular mass of the protein determined by electrospray ionization mass spectrometry (ESI-MS) was 6 494Da. PgAFP showed a cationic character with an estimated pI value of 9.22. Upon chemical and enzymatic treatments of PgAFP, no evidence for N- or O-glycosylations was obtained. Five partial sequences of PgAFP were obtained by Edman degradation and by ESI-MS/MS after trypsin and chymotrypsin digestions. Using degenerate primers from these peptide sequences, a segment of 70bp was amplified by PCR from pgafp gene. 5'- and 3'-ends of pgafp were obtained by RACE-PCR with gene-specific primers designed from the 70bp segment. The complete pgafp sequence of 404bp was obtained using primers designed from 5'- and 3'-ends. Comparison of genomic and cDNA sequences revealed a 279bp coding region interrupted by two introns of 63 and 62bp. The precursor of the antifungal protein consists of 92 amino acids and appears to be processed to the mature 58 amino acids PgAFP. The deduced amino acid sequence of the mature protein shares 79% identity to the antifungal protein Anafp from Aspergillus niger. PgAFP is a new protein that belongs to the group of small, cysteine-rich, and basic proteins with antifungal activity produced by ascomycetes. Given that P. chrysogenum is regarded as safe mold commonly found in foods, PgAFP may be useful to prevent growth of toxigenic molds in food and agricultural products.

  11. Antifreeze Protein (AFP) and Antifreeze Glycoprotein (AFGP) Kinetics at the Ice/Solution Interface

    NASA Astrophysics Data System (ADS)

    Zepeda, Salvador; Nakaya, Hiroyuki; Uda, Yukihiro; Yokoyama, Etsuro; Furukawa, Yoshinori

    2007-03-01

    AFPs and AFGPs found in some fish, plants and insects are a necessary tool for surviving sub-freezing environments. They occur in a wide range of compositions and structure, but to some extent they all accomplish the same functions: they suppress the freezing temperature, inhibit recrystallization, and modify ice crystal growth. Here, we observe the exact location of AFGPs, Type I and Type III AFPs by 1-directional growth experiments using fluorescence and phase contrast microscopy as well as free growth experiments using 3-d confocal microscopy. In all cases, the proteins clearly adsorb at the interface. By comparing the fluorescent image with the corresponding phase contrast image we find that AFGPs incorporate only into the solid in veins and not into the ice lattice structure. Type I AFPs show similar behavior as AFGPs, but type III AFPs adsorb to specific planes within the ice lattice. We have also calculated the diffusion constants and the surface adsorption concentration from both types of experiments. Our results indicated that the different types of AFPs or AFGPs accomplish essentially the same function in slightly different ways and that it is not necessary for the protein adsorption to the ice interface to be as rigid as once thought.

  12. Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1α activation

    PubMed Central

    Ambade, Aditya; Satishchandran, Abhishek; Szabo, Gyongyi

    2016-01-01

    Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro-inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated in livers of alcohol-fed DEN-injected mice compared to controls. In livers with tumors, loss of miR-122 expression with a significant up-regulation of miR-122 target HIF-1α is seen. We conclude that alcoholic steatohepatitis accelerates hepatobiliary tumors with characteristic molecular features of HCC by up-regulating inflammation, cell proliferation, stemness, and miR-122 loss. PMID:26888602

  13. Lineage restriction and differentiation of human embryonic stem cells into hepatic progenitors and zone 1 hepatocytes.

    PubMed

    Pei, Haiyun; Yang, Yinxiang; Xi, Jiafei; Bai, Zongliang; Yue, Wen; Nan, Xue; Bai, Cixian; Wang, Yunfang; Pei, Xuetao

    2009-03-01

    Human embryonic stem (hES) cells can self-renew, which enables them to have considerable expansion potential, and are pluripotent. If their differentiation can be controlled, they can offer promise for clinical programs in cell therapies. A novel strategy has been developed to derive early hepatocytic lineage stages from hES cells using four sequential inducing steps lasting 16 days. First, embryoid bodies (EBs) were generated by growing hES cells in suspension for 2 days; second, EBs were lineage restricted to definitive endoderm with 3 days of treatment with human activin A; third, cells were differentiated further by coculturing for 5 days with human fetal liver stromal cells (hFLSCs) made transgenic to stably release basic fibroblast growth factor (bFGF); fourth, treating them for 6 days with soluble signals comprised of hFLSC-derived bFGF, hepatocyte growth factor, oncostatin M, and dexamethasone. Induced cells displayed morphological, immunohistochemical, and biochemical characteristics of hepatocytic committed progenitors and of early lineage stage hepatocytes found in zone 1 of the liver acinus. They expressed alpha-fetoprotein, albumin, cytokeratin 18, glycogen, a fetal P450 isoform, and CYP1B1, and demonstrated indocyanine green uptake and excretion. In conclusion, we have developed a novel method to lineage restrict hES cells into early lineage stages of hepatocytic fates.

  14. [A case of AFP and PIVKA-II producing gastric carcinoma].

    PubMed

    Tanaka, Hiroki; Ishii, Suguru; Akutsu, Noriyuki; Ohashi, Hirokazu; Tokuno, Tetsuya; Suzuki, Takashi; Okuda, Hiroyuki; Shinomura, Yasuhisa; Imai, Kohzoh

    2006-04-01

    A 71-year-old man was admitted to our hospital with edema of the ambilateral crura and liver dysfunction. Serum levels of AFP and PIVKA-II were both abnormally high. An abdominal CT revealed many low density masses in both lobes of the liver. Endoscopic examination and gastric radiography showed a Type 1 tumor in the fornix of the stomach. Biopsy specimen showed poorly differentiated adenocarcinoma. Immunohistochemical stains demonstrated the presence of AFP and PIVKA-II in tumor cells. A diagnosis of AFP and PIVKA-II producing gastric carcinoma with liver metastasis was made and the internal use of S-1 was started. The result of treatment was determined to be partial response. However, the condition of his entire body gradually worsened and he died of hepatic insufficiency.

  15. Synergistic Activity of the Plant Defensin HsAFP1 and Caspofungin against Candida albicans Biofilms and Planktonic Cultures

    PubMed Central

    Harvey, Peta J.; Craik, David J.; Spincemaille, Pieter; Cassiman, David; Braem, Annabel; Vleugels, Jozef; Nibbering, Peter H.; Drijfhout, Jan Wouter; De Coninck, Barbara; Cammue, Bruno P. A.; Thevissen, Karin

    2015-01-01

    Plant defensins are small, cysteine-rich peptides with antifungal activity against a broad range of yeast and fungi. In this study we investigated the antibiofilm activity of a plant defensin from coral bells (Heuchera sanguinea), i.e. HsAFP1. To this end, HsAFP1 was heterologously produced using Pichia pastoris as a host. The recombinant peptide rHsAFP1 showed a similar antifungal activity against the plant pathogen Fusarium culmorum as native HsAFP1 purified from seeds. NMR analysis revealed that rHsAFP1 consists of an α-helix and a triple-stranded antiparallel β-sheet stabilised by four intramolecular disulfide bonds. We found that rHsAFP1 can inhibit growth of the human pathogen Candida albicans as well as prevent C. albicans biofilm formation with a BIC50 (i.e. the minimum rHsAFP1 concentration required to inhibit biofilm formation by 50% as compared to control treatment) of 11.00 ± 1.70 μM. As such, this is the first report of a plant defensin exhibiting inhibitory activity against fungal biofilms. We further analysed the potential of rHsAFP1 to increase the activity of the conventional antimycotics caspofungin and amphotericin B towards C. albicans. Synergistic effects were observed between rHsAFP1 and these compounds against both planktonic C. albicans cells and biofilms. Most notably, concentrations of rHsAFP1 as low as 0.53 μM resulted in a synergistic activity with caspofungin against pre-grown C. albicans biofilms. rHsAFP1 was found non-toxic towards human HepG2 cells up to 40 μM, thereby supporting the lack of a general cytotoxic activity as previously reported for HsAFP1. A structure-function study with 24-mer synthetic peptides spanning the entire HsAFP1 sequence revealed the importance of the γ-core and its adjacent regions for HsAFP1 antibiofilm activity. These findings point towards broad applications of rHsAFP1 and its derivatives in the field of antifungal and antibiofilm drug development. PMID:26248029

  16. Synergistic Activity of the Plant Defensin HsAFP1 and Caspofungin against Candida albicans Biofilms and Planktonic Cultures.

    PubMed

    Vriens, Kim; Cools, Tanne L; Harvey, Peta J; Craik, David J; Spincemaille, Pieter; Cassiman, David; Braem, Annabel; Vleugels, Jozef; Nibbering, Peter H; Drijfhout, Jan Wouter; De Coninck, Barbara; Cammue, Bruno P A; Thevissen, Karin

    2015-01-01

    Plant defensins are small, cysteine-rich peptides with antifungal activity against a broad range of yeast and fungi. In this study we investigated the antibiofilm activity of a plant defensin from coral bells (Heuchera sanguinea), i.e. HsAFP1. To this end, HsAFP1 was heterologously produced using Pichia pastoris as a host. The recombinant peptide rHsAFP1 showed a similar antifungal activity against the plant pathogen Fusarium culmorum as native HsAFP1 purified from seeds. NMR analysis revealed that rHsAFP1 consists of an α-helix and a triple-stranded antiparallel β-sheet stabilised by four intramolecular disulfide bonds. We found that rHsAFP1 can inhibit growth of the human pathogen Candida albicans as well as prevent C. albicans biofilm formation with a BIC50 (i.e. the minimum rHsAFP1 concentration required to inhibit biofilm formation by 50% as compared to control treatment) of 11.00 ± 1.70 μM. As such, this is the first report of a plant defensin exhibiting inhibitory activity against fungal biofilms. We further analysed the potential of rHsAFP1 to increase the activity of the conventional antimycotics caspofungin and amphotericin B towards C. albicans. Synergistic effects were observed between rHsAFP1 and these compounds against both planktonic C. albicans cells and biofilms. Most notably, concentrations of rHsAFP1 as low as 0.53 μM resulted in a synergistic activity with caspofungin against pre-grown C. albicans biofilms. rHsAFP1 was found non-toxic towards human HepG2 cells up to 40 μM, thereby supporting the lack of a general cytotoxic activity as previously reported for HsAFP1. A structure-function study with 24-mer synthetic peptides spanning the entire HsAFP1 sequence revealed the importance of the γ-core and its adjacent regions for HsAFP1 antibiofilm activity. These findings point towards broad applications of rHsAFP1 and its derivatives in the field of antifungal and antibiofilm drug development. PMID:26248029

  17. [A surgically resected case of AFP and PIVKA-II producing gastric cancer with hepatic metastasis].

    PubMed

    Tomono, Ayako; Wakahara, Tomoyuki; Kanemitsu, Kiyonori; Toyokawa, Akihiro; Teramura, Kazuhiro; Iwasaki, Takeshi

    2013-05-01

    A 78-year-old man was admitted for workup for a liver tumor. Both serum AFP and PIVKA-II levels were high (2260ng/ml and 806mAU/ml, respectively). Contrast-enhanced CT scan and MRI using Gd-EOB-DTPA demonstrated a liver tumor in segment 6 resembling the imaging patterns of hepatocellular carcinoma (HCC), while the upper gastrointestinal endoscopy revealed a type 2 gastric cancer in the gastric antrum. Although the liver metastasis of the gastric cancer was undeniable, we performed partial resection of segment 6 of the liver and distal gastrectomy under a preoperative diagnosis of double cancer. Histopathologically, gastric tumor consisted of two components, such as well differentiated adenocarcinoma and hepatoid adenocarcinoma. The histology of the liver tumor was similar to that of the hepatoid component in the stomach lesion. Immunohistochemical staining revealed both the gastric and the liver tumors to be positive for AFP and PIVKA-II, yielding a definite diagnosis of AFP and PIVKA-II producing gastric cancer with liver metastasis. Because many cases of this disease have liver metastases at presentation with confusing images with HCC, the diagnosis of liver tumors should be carefully differentiated in the gastric cancer patients with liver tumors, high serum AFP and PIVKA-II levels.

  18. ENVIRONMENTAL TECHNOLOGY VERIFICATION, TEST REPORT OF CONTROL OF BIOAEROSOLS IN HVAC SYSTEMS, AIRFLOW PRODUCTS AFP30

    EPA Science Inventory

    The Environmental Technology Verification report discusses the technology and performance of the AFP30 air filter for dust and bioaerosol filtration manufactured by Airflow Products. The pressure drop across the filter was 62 Pa clean and 247 Pa dust loaded. The filtration effici...

  19. Influence of 4-hydroxynonenal and spleen cells on primary hepatocyte culture and a novel liver-derived cell line resembling hepatocyte stem cells.

    PubMed

    Cipak, Ana; Borovic, Suzana; Jaganjac, Morana; Bresgen, Nikolaus; Kirac, Iva; Grbesa, Ivana; Mrakovcic, Lidija; Cindric, Marina; Scukanec-Spoljar, Mira; Gall-Troselj, Koraljka; Coric, Marijana; Eckl, Peter; Zarkovic, Neven

    2010-01-01

    Liver is a unique mammalian organ with a great capacity of regeneration related to its function. After surgical resection or injury, hepatic cells, especially hepatocytes, can proliferate rapidly to repair the damage and to regenerate the structure without affecting the function of the liver. Loss of catalase activity during regeneration indicates that oxidative stress is present in the liver not only in pathological conditions but also as a 'physiological' factor during regeneration. As we have shown in our previous work, liver stem cell-like cells treated with 4-hydroxynonenal (HNE), a cytotoxic and growth regulating lipid peroxidation product, recover in the presence of spleen cells. In the current study we characterized this novel cell line as liver-derived progenitor/oval-like cells, (LDP/OCs), i.e. functional liver stem-like cells. We showed that LDP/OC were OV6 positive, with abundant glycogen content in the cytoplasm and expressed alpha-fetoprotein, albumin, biliverdin reductase and gamma-glutamyl transferase. Also, we compared their growth in vitro with the growth of cultured primary hepatocytes stressed with HNE and co-cultured with autologous spleen cells. The influence of spleen cells on HNE-treated primary hepatocytes and on LDP/OCs showed that spleen cells support in a similar manner the recovery of both types of liver cells indicating their important role in regeneration. Hence, LDP/OC cells may provide a valuable tool to study cell interactions and the role on HNE in liver regeneration.

  20. STS-39 AFP-675 CIRRIS-1A in OV-103's payload bay (PLB)

    NASA Technical Reports Server (NTRS)

    1991-01-01

    STS-39's Air Force Program 675 (AFP-675) Uniformly Redundant Array (URA) and Cryogenic Infrared Radiance Instrumentation for Shuttle 1A (CIRRIS-1A) mounted on the experiment support system (ESS) pallet are documented in Discovery's, Orbiter Vehicle (OV) 103's, payload bay (PLB). Part of the ESS pallet power distribution system thermal covering is visible at the bottom of the frame. AFP-675 is a Department of Defense (DOD)-sponsored collection of experiments whose objective is to gather data on the Earth's atmosphere (aurora, Earth limb, and airglow), celestial objects, and the environment in and around the PLB. In the background are the aft PLB bulkhead, the vertical tail, and the orbital maneuvering system (OMS) pods.

  1. STS-39 AFP-675 and STP-1 MPESS in OV-103's payload bay (PLB)

    NASA Technical Reports Server (NTRS)

    1991-01-01

    An overview of Discovery's, Orbiter Vehicle (OV) 103's, aft payload bay (PLB) documents a variety of STS-39's payloads. In the foreground is the Space Test Payload 1 (STP-1) multipurpose experiment support structure (MPESS) with the Spacecraft Kinetic Infrared Test (SKIRT) (left), ascent particle monitor (APM) (center), and advanced liquid feed experiment (ALFE) (two canisters) visible. Behind the STP-1 is the Air Force Program 675 (AFP-675) experiment support structure (ESS) with ESS tape recorders (left), Uniformly Redundant Array (URA) (front),and Cryogenic Infrared Radiance Instrumentation for Shuttle 1A (CIRRIS-1A) (center back) visible. The ESS pallet power distribution system thermal covering (gold-colored) is visible at the bottom. AFP-675 is a Department of Defense (DOD)-sponsored collection of experiments whose objective is to gather data on the Earth's atmosphere (aurora, Earth limb, and airglow), celestial objects, and the environment in and around the PLB. In the backgroun

  2. Forming Simulation of Thick AFP Laminates and Comparison with Live CT Imaging

    NASA Astrophysics Data System (ADS)

    Leutz, Daniel; Vermilyea, Mark; Bel, Sylvain; Hinterhölzl, Roland

    2016-08-01

    Automated fiber placement (AFP) process can be used to manufacture laminates by laying up unidirectional slit tapes along a desired path and placing multiple layers on top of each other. Usually, the slit tapes are placed direct onto the tooling to attain the final part geometry. Alternatively, the laminate can be built up on a planar substrate and can be subsequently formed into the final shape. This kind of processing allows manufacturing highly curved parts, which may not be possible with the direct placement. In the present work a forming simulation of thick AFP laminates is developed to predict the tapes' orientations and delamination as well as transverse tape spread-ups and separations during the forming process. The simulation model is built up through the material characterization experiments. Validation is performed comparing the results of the simulation vs. the experimental forming on two generic geometries. An optical inspection is made on the external layers of the laminates. In a second step, live computer tomography (CT) scans are used to inspect the tapes within an AFP laminate during forming of an L- and a Z-flange. Tapes re-orientation, gaps and tapes widening are observed experimentally and compared to the simulation results. The simulation is capable to predict the tows orientation and provides indicators concerning the tows spread-up and separation.

  3. Cloning and expression of a novel antifreeze protein AFP72 from the beetle Tenebrio molitor.

    PubMed

    Yan, Qing-Hua; Yang, Li; Wang, Qing; Zhang, Hui-Rong; Shao, Qiang

    2012-01-01

    A novel antifreeze protein AFP72 cDNA (GenBbank accession No. AY929389) was obtained by RT-PCR from Tenebrio molitor. The 216 bp fragment encodes a protein of 72 amino acid residues. Sequence analysis revealed that the cDNA displays a high degree of homology with T. molitor antifreeze proteins, ranging up to 90.78%. Recombinant plasmids pMAL-p2X-afp72 and pMAL-c2X-afp72 were transferred into E. coil TBI to induce a MBP fusion protein by IPTG. The target fusion protein was released from the periplasm and cytoplasm by the cold osmotic shock procedure and sonication respectively. The content of the fusion protein came up to 38.9 and 41.5% of the total dissolved protein, respectively. The fusion protein was purified through an amylose affinity column, and incised by factor Xa. Molecular sieve chromatography was used to achieve a high state of purity of the target protein. The purified target protein displayed a single band in SDS-PAGE. The fusion protein was shown to increase resistance to low temperatures in bacteria. This finding could help in further investigations of the properties and function of antifreeze proteins. PMID:23113345

  4. Self-oscillatory ice crystal growth in antifreeze protein (AFP) and glycoprotein (AFGP) solutions

    NASA Astrophysics Data System (ADS)

    Zepeda, Salvador; Nakaya, Hiroyuki; Uda, Yukihiro; Yokoyama, Etsuro; Furukawa, Yoshinori

    2006-03-01

    AFPs and AFGPs allow many organisms including fish, plants and insects to survive sub-freezing environments. They occur in a wide range of compositions and structure, but to some extent they all accomplish the same functions: they suppress the freezing temperature, inhibit recrystallization, and modify ice crystal growth. A complete description of the AFGP/AFP surface mechanism as well as other ice surface phenomenon has eluded scientists primarily due to a lack of direct surface studies. We study ice crystal growth in AFGP and AFP solutions with phase contrast microscopy during free solution growth under various conditions including microgravity. Free-solution growth experiments show an anisotropic self-oscillatory growth mode of the steps and interface near the freezing temperature and enhancement of the growth rates in the c-axis. These results contradict the previous ?tight-binding? mechanism thought to be responsible for antifreeze function. To study the effects of temperature driven convective flows on the interface kinetics, microgravity experiments were performed in a jet airplane during a parabolic flight path. Step propagation on the basal plane slows down considerably when entering the microgravity condition and reaches a critical condition just below 0.2g.

  5. [Demonstration of PIVKA-II and AFP production by gastric cancer by indirect immunoenzymatic staining of paraffin sections].

    PubMed

    Nakamura, K; Sakizono, K; Oita, T; Kudo, M; Shirane, H; Uchida, H; Kasakura, S

    1991-06-01

    The patient had elevated plasma PIVKA-II and serum AFP levels. However, no tumor was detected with an ultrasonography, angiography, abdominal computed tomography (CT), and magnetic resonance imaging (MR). Gastric endoscopic examination disclosed gastric cancer and then subtotal gastrectomy was done. Shortly after the surgery, both plasma PIVKA-II and serum AFP levels returned to each normal level. The extirpated tumor revealed histologically immature and mature cancer cells. It was pathologically diagnosed as IIc early cancer. The localization of PIVKA-II and AFP in gastric cancer cells was demonstrated by the immunostaining method using monoclonal antibody. Taken together, these results indicate that cancer cells may produce PIVKA-II or AFP in this patient.

  6. Reasons and circumstances for the late notification of Acute Flaccid Paralysis (AFP) cases in health facilities in Luanda

    PubMed Central

    Macama, Arciolanda; Okeibunor, Joseph; Grando, Silvia; Djibaoui, Karim; Yameogo, Robert Koudounoaga; Morais, Alda; Gasasira, Alex Ntale; Mbaye, Salla; Mihigo, Richard; Nshimirimana, Deo

    2014-01-01

    Introduction As the polio eradication effort enters the end game stage, surveillance for Acute Flaccid Paralysis in children becomes a pivotal tool. Thus given the gaps in AFP surveillance as identified in the cases of late notification, this study was designed to explore the reasons and circumstances responsible for late notification of AFP and collection of inadequate stools (more than 14 days of onset of paralysis until collection of the 2nd stool specimen) of AFP cases in health facilities equipped to manage AFP cases. Methods Eleven AFP cases with inadequate stools were reported from January 2 to July 8, 2012 - Epidemiological Weeks 1-27. The families of these cases were interviewed with an in-depth interview guide. The staff of the seven health units, where they later reported, was also enlisted for the study which used in-depth interview guide in eliciting information from them. Results Ignorance and wrong perception of the etiology of the cases as well as dissatisfaction with the health units as the major reasons for late reporting of AFP cases. The first port of call is usually alternative health care system such as traditional healers and spiritualists because the people hold the belief that the problem is spiritually induced. The few, who make it to health units, are faced with ill equipped rural health workers who wait for the arrival of more qualified staff, who may take days to do so. Conclusion An understanding of the health seeking behavior of the population is germane to effective AFP surveillance. There is thus a need to tailor AFP surveillance to the health seeking behavior of the populations and expand it to community structures. PMID:25426197

  7. Growth inhibition and stability of PgAFP from Penicillium chrysogenum against fungi common on dry-ripened meat products.

    PubMed

    Delgado, Josué; Acosta, Raquel; Rodríguez-Martín, Andrea; Bermúdez, Elena; Núñez, Félix; Asensio, Miguel A

    2015-07-16

    Dry-ripened foods favor the development of a superficial fungal population that may include toxigenic molds. To combat unwanted molds, an antifungal protein from Penicillium chrysogenum (PgAFP) can be useful. The aim of the present work was to study the antimicrobial activity of PgAFP against microorganisms common in dry-ripened foods, and to evaluate its sensitivity to proteolytic enzymes and heat treatments that may be applied to foods, as well as to different pH values. The inhibitory effect of the purified protein on 38 microbial strains grown in culture medium was determined. PgAFP sensitivity to various proteases, heat treatments, and preincubation at different pH values was tested by means of the residual activity on selected reference strains. Inhibitory activity of PgAFP against unwanted molds was tested in a dry-fermented sausage. This protein exhibited potent inhibitory activity against unwanted molds, including the main mycotoxin-producing species of Aspergillus and Penicillium of concern for dry-ripened foods. PgAFP withstood most proteases, intense heat and a wide range of pH values. PgAFP efficiently reduced counts of A. flavus and P. restrictum inoculated on a dry-fermented sausage. This protein can be of interest to control hazardous molds in dry-ripened foods.

  8. Cryoprotective effect of an insect antifreeze protein MpAFP 698 and its mutants from the desert beetle Microdera punctipennis.

    PubMed

    Jiang, M; Ma, J; Qiu, L M

    2011-01-01

    An insect antifreeze protein, MpAFP698, from the desert beetle Microdera punctipennis, shares 77% similarity with TmTHP (YL-3) from Tenebrio molitor. The predicted tertiary structure for MpAFP698 was modeled as a regular A-helix with TCT motifs arrayed to form the putative ice-binding surface. This model was validated via site-directed mutagenesis. The results suggest that the desert beetle in central Asia has evolved antifreeze proteins similar to those from North America continent. In an additional study, the recombinant MpAFP698 and its mutants were expressed in Escherichia coli strain BL21 (DE3). The thermal hysteresis activity of MpAFP698 was 1.73 degree C at 1.0 mg/ml. MpAFP698 was also tested by in vitro antifreeze activity assay to evaluate its cryoprotective effect at -20 degree C. MpAFP698 displays high cryoprotective effect on bacteria cells at freezing temperatures. PMID:22020466

  9. [Tumor markers for hepatocellular carcinoma].

    PubMed

    Tateishi, Ryosuke; Enooku, Kenichiro; Shiina, Shuichiro; Koike, Kazuhiko

    2012-05-01

    Three tumor markers for hepatocellular carcinoma (HCC) are available in Japan: alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonists-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). Although AFP has drawbacks in its specificity, it is widely utilized in treatment evaluation and prognosis prediction. PIVKA-II is a unique marker that does not correlate with AFP value and can predict microvascular invasion. AFP-L3 is a highly specific marker and strong predictor of poor prognosis. These three markers are indispensable in every aspect of clinical practice of hepatocellular carcinoma including surveillance, diagnosis, treatment evaluation, and prognosis prediction.

  10. Pluripotent Stem Cell-Derived Hepatocyte-Like Cells

    PubMed Central

    Schwartz, R. E.; Fleming, H.E.; Bhatia, S. N.

    2014-01-01

    Liver disease is an important clinical problem, impacting over 30 million Americans and over 600 million people worldwide. It is the 12th leading cause of death in the United States and the 16th worldwide. Due to a paucity of donor organs, several thousand Americans die yearly while waiting for liver transplantation. Unfortunately, alternative tissue sources such as fetal hepatocytes and hepatic cell lines are unreliable, difficult to reproduce, and do not fully recapitulate hepatocyte phenotype and function. As a consequence, alternative cell sources that do not have these limitations have been sought. Human embryonic stem (hES) cell- and induced pluripotent stem (iPS) cell-derived hepatocyte-like cells may enable cell based therapeutics, the study of the mechanisms of human disease and human development, and provide a platform for pharmacology and toxicology drug screening. iPS cells can be differentiated in a stepwise fashion with high efficiency and reproducibility into hepatocyte-like cells that exhibit morphologic and phenotypic characteristics of hepatocytes. In addition, iPS-derived hepatocyte-like cells possess some functional hepatic activity as they secrete urea, alpha-1-antitrypsin, and albumin. However, the combined phenotypic and functional traits exhibited by iPS-derived hepatocyte-like cells resemble a relatively immature hepatic phenotype that more closely resembles that of fetal hepatocytes rather than adult hepatocytes. Specifically, iPS-derived hepatocyte-like cells express fetal markers such as alpha fetoprotein and lack key mature hepatocyte functions, as reflected by drastically reduced activity (0.1%) of many detoxification enzymes (i.e. CYP2A6, CYP3A4). These key differences between iPS-derived hepatocyte-like cells and adult hepatocytes have limited the use of stem cells as a renewable source of functional adult human hepatocytes for in vitro and in vivo applications. Unfortunately, the developmental pathways that control hepatocyte

  11. Non-polio enteroviruses associated with acute flaccid paralysis (AFP) and facial paralysis (FP) cases in Romania, 2001-2008.

    PubMed

    Persu, Ana; Băicuş, Anda; Stavri, Simona; Combiescu, Mariana

    2009-01-01

    Acute flaccid paralysis is a complex clinical syndrome, with a wide variety of possible etiologies and with clinical manifestations that can vary according to age or geographical region. Enteroviruses (polioviruses and non-polio enteroviruses) are among the viral agents that can cause AFP. AFP surveillance is important for public health through its use in monitoring poliomyelitis, in the context of the Global Initiative to eradicate this disease. The current paper aims to assess the non-polio enteroviruses (NPEV) association with AFP and FP cases registered in Romania in the period 2001-2008 and to identify prevalent serotypes. Within the framework of Surveillance of AFP Cases Program, were collected samples from 579 children with AFP or FP (3.069 samples). The samples were processed and inoculated onto two types of cell culture (RD and L20B), according to WHO protocol. The identification of isolated viruses has been done by the reaction of seroneutralization with pools of specific antiserum and then with monospecific antiserum for confirmation. NPEV were isolated from 58 cases (123 positive samples). During the analyzed period, 23 NPEV serotypes have circulated (15 Echo serotypes and 8 coxsackie serotypes). The most frequently identified were the Echoviruses 13 and 11 and the coxsackie A viruses. 88% of positive cases have occurred in children between 1 and 5 years. As seasonal distribution, the peak of NPEV circulation was in the months August-September (36.2%). The paper provides information about NPEV circulation in Romania in the past 8 years, about its association with the AFP and FP and it indicates the need for monitoring NPEV circulation even after the eradication of poliomyelitis.

  12. Stem-loop oligonucleotide beacons as switches for amplifying-fluorescent-polymer-based biological warfare sensors

    NASA Astrophysics Data System (ADS)

    Clinkenbeard, Kenneth D.; Ramachandran, Akhilesh; Malayer, Jerry R.; Moon, Joong Ho; Hancock, Lawrence F.

    2003-09-01

    Sensors that are exceptionally sensitive with real-time outputs and minimal consumption of reagents are needed to continuously monitor air and water against bioterrorist incidents. Amplifying fluorescent polymers (AFP) provide exceptionally sensitive real-time reagentless sensor platforms as applied to detection of nitroaromatic explosives. This platform technology has the potential to be adapted to detect biological warfare (BW) agents by covalently attaching the 5" end of stem-loop molecular beacons to AFP as DNA hybridization signal transduction switches. Molecular beacons with loop sequences specific for sequence signatures of a target BW agent are configured with a quencher on the end of the 3" arm of the stem-loop. The AFP is quenched in the absence of target DNA, but upon hybridization with target the stem is melted, the duplex loop extended, and the AFP dequenched. This signal transduction is reversible upon removal of the target sequence with the molecular beacon reforming the stem-loop conformation. Proof-of-concept research has demonstrated that molecular beacons for signature sequences of Francisella tularensis result in correct identification of the presence of this agent in samples, but no false positives were seen with Escherichia coli.

  13. A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome

    PubMed Central

    Petit, François M; Hébert, Marylise; Picone, Olivier; Brisset, Sophie; Maurin, Marie-Laure; Parisot, Frédéric; Capel, Liliane; Benattar, Clarisse; Sénat, Marie-Victoire; Tachdjian, Gérard; Labrune, Philippe

    2009-01-01

    Alpha feto-protein (AFP) is a major plasma protein produced by the yolk sac and the liver during the fetal period. During the second trimester of pregnancy, APF and βhCG serum concentrations are commonly used for screening Down syndrome. AFP deficiency is rare (estimated to be 1/105 000 newborns) and only one sequence alteration has previously been reported in the AFP gene. We report a new mutation in exon 5 of the AFP gene, leading to a total absence of AFP on 2nd-trimester maternal serum screening for Down syndrome, confirmed on the amniotic fluid. Despite this, fetal development and birth were normal. After PCR-amplification, the whole AFP gene was sequenced. The new mutation was a guanine to adenine transition in position 543 creating a premature stop codon in position 181. In order to search for eventual modifications of the amniotic fluid profile, proteins were separated by electrophoresis and compared with 10 normal amniotic fluids sampled at the same developmental age (18 weeks). In the amniotic fluid of our patient albumin rate was reduced whereas alpha1 and beta protein fractions were increased, suggesting that AFP deficiency may modify the distribution of protein fractions. This observation emphasizes the complex molecular mechanisms of compensation of serum protein deficiency. Studies on other families with AFP deficiency are necessary to confirm this observation. PMID:18854864

  14. Increased chitin biosynthesis contributes to the resistance of Penicillium polonicum against the antifungal protein PgAFP.

    PubMed

    Delgado, Josué; Owens, Rebecca A; Doyle, Sean; Asensio, Miguel A; Núñez, Félix

    2016-01-01

    Antifungal proteins from molds have been proposed as a valuable tool against unwanted molds, but the resistance of some fungi limits their use. Resistance to antimicrobial peptides has been suggested to be due to lack of interaction with the mold or to a successful response. The antifungal protein PgAFP produced by Penicillium chrysogenum inhibits the growth of various ascomycetes, but not Penicillium polonicum. To study the basis for resistance to this antifungal protein, localization of PgAFP and metabolic, structural, and morphological changes were investigated in P. polonicum. PgAFP bound the outer layer of P. polonicum but not regenerated chitin, suggesting an interaction with specific molecules. Comparative two-dimensional gel electrophoresis (2D-PAGE) and comparative quantitative proteomics revealed changes in the relative abundance of several proteins from ribosome, spliceosome, metabolic, and biosynthesis of secondary metabolite pathways. The proteome changes and an altered permeability reveal an active reaction of P. polonicum to PgAFP. The successful response of the resistant mold seems to be based on the higher abundance of protein Rho GTPase Rho1 that would lead to the increased chitin deposition via cell wall integrity (CWI) signaling pathway. Thus, combined treatment with chitinases could provide a complementary means to combat resistance to antifungal proteins.

  15. Heterologous expression of antifreeze protein gene AnAFP from Ammopiptanthus nanus enhances cold tolerance in Escherichia coli and tobacco.

    PubMed

    Deng, Long-Qun; Yu, Hao-Qiang; Liu, Yan-Ping; Jiao, Pei-Pei; Zhou, Shu-Feng; Zhang, Su-Zhi; Li, Wan-Chen; Fu, Feng-Ling

    2014-04-10

    Antifreeze proteins are a class of polypeptides produced by certain animals, plants, fungi and bacteria that permit their survival under the subzero environments. Ammopiptanthus nanus is the unique evergreen broadleaf bush endemic to the Mid-Asia deserts. It survives at the west edge of the Tarim Basin from the disappearance of the ancient Mediterranean in the Tertiary Period. Its distribution region is characterized by the arid climate and extreme temperatures, where the extreme temperatures range from -30 °C to 40 °C. In the present study, the antifreeze protein gene AnAFP of A. nanus was used to transform Escherichia coli and tobacco, after bioinformatics analysis for its possible function. The transformed E. coli strain expressed the heterologous AnAFP gene under the induction of isopropyl β-D-thiogalactopyranoside, and demonstrated significant enhancement of cold tolerance. The transformed tobacco lines expressed the heterologous AnAFP gene in response to cold stress, and showed a less change of relative electrical conductivity under cold stress, and a less wilting phenotype after 16 h of -3 °C cold stress and thawing for 1h than the untransformed wild-type plants. All these results imply the potential value of the AnAFP gene to be used in genetic modification of commercially important crops for improvement of cold tolerance. PMID:24502990

  16. Heterologous expression of antifreeze protein gene AnAFP from Ammopiptanthus nanus enhances cold tolerance in Escherichia coli and tobacco.

    PubMed

    Deng, Long-Qun; Yu, Hao-Qiang; Liu, Yan-Ping; Jiao, Pei-Pei; Zhou, Shu-Feng; Zhang, Su-Zhi; Li, Wan-Chen; Fu, Feng-Ling

    2014-04-10

    Antifreeze proteins are a class of polypeptides produced by certain animals, plants, fungi and bacteria that permit their survival under the subzero environments. Ammopiptanthus nanus is the unique evergreen broadleaf bush endemic to the Mid-Asia deserts. It survives at the west edge of the Tarim Basin from the disappearance of the ancient Mediterranean in the Tertiary Period. Its distribution region is characterized by the arid climate and extreme temperatures, where the extreme temperatures range from -30 °C to 40 °C. In the present study, the antifreeze protein gene AnAFP of A. nanus was used to transform Escherichia coli and tobacco, after bioinformatics analysis for its possible function. The transformed E. coli strain expressed the heterologous AnAFP gene under the induction of isopropyl β-D-thiogalactopyranoside, and demonstrated significant enhancement of cold tolerance. The transformed tobacco lines expressed the heterologous AnAFP gene in response to cold stress, and showed a less change of relative electrical conductivity under cold stress, and a less wilting phenotype after 16 h of -3 °C cold stress and thawing for 1h than the untransformed wild-type plants. All these results imply the potential value of the AnAFP gene to be used in genetic modification of commercially important crops for improvement of cold tolerance.

  17. Preliminary data on an association between blood groups and serum markers used for the so-called "triple screening": free oestriol MoM values are decreased in rhesus-negative (Rh-) women.

    PubMed

    Sancken, U; Bartels, I

    2001-03-01

    The serum markers human chorionic gonadotrophin (hCG), alpha-fetoprotein (AFP) and unconjugated oestriol (uE3) in 606 rhesus-negative (Rh-) women have been compared with 18 960 controls. There were no significant differences in the distribution of hCG and AFP between these two cohorts. However the uE3 values in Rh- women were significantly lowered (median: 0.85 MoM).

  18. Prenatal Testing - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Arabic (العربية) Chinese - Simplified (简体中文) Chinese - Traditional (繁體中文) French (français) Hindi (हिन्दी) Japanese (日本語) Korean (한국어) ... 繁體中文 (Chinese - Traditional) Bilingual PDF Health Information Translations French (français) AFP (Alpha-Fetoprotein) Test Test AFP (alpha- ...

  19. STEM, STEM Education, STEMmania

    ERIC Educational Resources Information Center

    Sanders, Mark

    2009-01-01

    In this article, the author introduces integrative STEM (science, technology, engineering, and/or mathematics) education and discusses the importance of the program. The notion of integrative STEM education includes approaches that explore teaching and learning between/among any two or more of the STEM subject areas, and/or between a STEM subject…

  20. Stem Cells

    MedlinePlus

    Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  1. Extrarenal teratoid Wilms' tumor: two cases in unusual locations, one associated with elevated serum AFP.

    PubMed

    Song, Joon Seon; Kim, In Koo; Kim, Yong Man; Khang, Shin-Kwang; Kim, Kyu-Rae; Lee, Yonghee

    2010-01-01

    Teratoid Wilms' tumor is an unusual morphological entity characterized by a classic triphasic malignancy with predominantly heterologous tissue. The authors describe two cases of teratoid Wilms' tumor with an extrarenal site: one in a 13-year-old girl with vaginal spotting (patient 1) and another in a 1-day-old girl with a sacrococcygeal mass (patient 2). The tumors were located in the vagina and coccyx, respectively. Under the initial clinical diagnosis of sarcoma botryoides in patient 1 and teratoma in patient 2, the masses were removed. Microscopically, both tumors were composed of typical triphasic Wilms' tumor tissue with primitive cartilage and skeletal muscle, and squamous and columnar mucinous epithelia. The patient with sacrococcygeal mass (patient 2) had an elevated serum AFP level. The patients were given chemotherapy and have now remained disease free for 7 years 1 month, and 2 years 5 months after surgery, respectively. Familiarity with this rare variant of Wilms' tumor might be important in arriving at a correct diagnosis.

  2. The antifungal plant defensin RsAFP2 from radish induces apoptosis in a metacaspase independent way in Candida albicans.

    PubMed

    Aerts, An M; Carmona-Gutierrez, Didac; Lefevre, Sophie; Govaert, Gilmer; François, Isabelle E J A; Madeo, Frank; Santos, Renata; Cammue, Bruno P A; Thevissen, Karin

    2009-08-01

    We show that the antifungal plant defensin Raphanus sativus antifungal protein 2 (RsAFP2) from radish induces apoptosis and concomitantly triggers activation of caspases or caspase-like proteases in the human pathogen Candida albicans. Furthermore, we demonstrate that deletion of C. albicans metacaspase 1, encoding the only reported (putative) caspase in C. albicans, significantly affects caspase activation by the apoptotic stimulus acetic acid, but not by RsAFP2. To our knowledge, this is the first report on the induction of apoptosis with concomitant caspase activation by a defensin in this pathogen. Moreover, our data point to the existence of at least two different types of caspases or caspase-like proteases in C. albicans. PMID:19596007

  3. Environmental potential of the use of CO2 from alcoholic fermentation processes. The CO2-AFP strategy.

    PubMed

    Alonso-Moreno, Carlos; García-Yuste, Santiago

    2016-10-15

    A novel Carbon Dioxide Utilization (CDU) approach from a relatively minor CO2 emission source, i.e., alcoholic fermentation processes (AFP), is presented. The CO2 produced as a by-product from the AFP is estimated by examining the EtOH consumed per year reported by the World Health Organization in 2014. It is proposed that the extremely pure CO2 from the AFP is captured in NaOH solutions to produce one of the Top 10 commodities in the chemical industry, Na2CO3, as a good example of an atomic economy process. The novel CDU strategy could yield over 30.6Mt of Na2CO3 in oversaturated aqueous solution on using ca. 12.7Mt of captured CO2 and this process would consume less energy than the synthetic methodology (Solvay ammonia soda process) and would not produce low-value by-products. The quantity of Na2CO3 obtained by this strategy could represent ca. 50% of the world Na2CO3 production in one year. In terms of the green economy, the viability of the strategy is discussed according to the recommendations of the CO2Chem network, and an estimation of the CO2negative emission achieved suggests a capture of around 280.0Mt of CO2 from now to 2020 or ca. 1.9Gt from now to 2050. Finally, the results obtained for this new CDU proposal are discussed by considering different scenarios; the CO2 production in a typical winemaking corporation, the CO2 released in the most relevant wine-producing countries, and the use of CO2 from AFP as an alternative for the top Na2CO3-producing countries. PMID:27300565

  4. Environmental potential of the use of CO2 from alcoholic fermentation processes. The CO2-AFP strategy.

    PubMed

    Alonso-Moreno, Carlos; García-Yuste, Santiago

    2016-10-15

    A novel Carbon Dioxide Utilization (CDU) approach from a relatively minor CO2 emission source, i.e., alcoholic fermentation processes (AFP), is presented. The CO2 produced as a by-product from the AFP is estimated by examining the EtOH consumed per year reported by the World Health Organization in 2014. It is proposed that the extremely pure CO2 from the AFP is captured in NaOH solutions to produce one of the Top 10 commodities in the chemical industry, Na2CO3, as a good example of an atomic economy process. The novel CDU strategy could yield over 30.6Mt of Na2CO3 in oversaturated aqueous solution on using ca. 12.7Mt of captured CO2 and this process would consume less energy than the synthetic methodology (Solvay ammonia soda process) and would not produce low-value by-products. The quantity of Na2CO3 obtained by this strategy could represent ca. 50% of the world Na2CO3 production in one year. In terms of the green economy, the viability of the strategy is discussed according to the recommendations of the CO2Chem network, and an estimation of the CO2negative emission achieved suggests a capture of around 280.0Mt of CO2 from now to 2020 or ca. 1.9Gt from now to 2050. Finally, the results obtained for this new CDU proposal are discussed by considering different scenarios; the CO2 production in a typical winemaking corporation, the CO2 released in the most relevant wine-producing countries, and the use of CO2 from AFP as an alternative for the top Na2CO3-producing countries.

  5. Hydrometallurgical recovery of heavy metals from low grade automobile shredder residue (ASR): An application of advanced Fenton process (AFP).

    PubMed

    Singh, Jiwan; Lee, Byeong-Kyu

    2015-09-15

    To investigate the leaching and recovery of heavy metals from low-grade automobile shredder residue (ASR), the effects of nitric acid (HNO3) and hydrogen peroxide (H2O2) concentrations, liquid/solid (L/S) ratio, leaching temperature and ASR particle size fractions on the heavy metal leaching rate were determined. The heavy metals were recovered by fractional precipitation and advanced Fenton process (AFP) at different pHs. The toxicity characteristic leaching procedure (TCLP) test was also performed in the residue remaining after heavy metal leaching to evaluate the potential toxicity of ASR. The heavy metal leaching efficiency was increased with increasing HNO3 and H2O2 concentrations, L/S ratio and temperature. The heavy metal leaching efficiencies were maximized in the lowest ASR size fraction at 303 K and L/S ratio of 100 mL/g. The kinetic study showed that the metal leaching was best represented by a second-order reaction model, with a value of R(2) > 0.99 for all selected heavy metals. The determined activation energy (kJ/mol) was 21.61, 17.10, 12.15, 34.50, 13.07 and 11.45 for Zn, Fe, Ni, Pb, Cd and Cr, respectively. In the final residue, the concentrations of Cd, Cr and Pb were under their threshold limits in all ASR size fractions. Hydrometallurgical metal recovery was greatly increased by AFP up to 99.96% for Zn, 99.97% for Fe, 95.62% for Ni, 99.62% for Pb, 94.11% for Cd and 96.79% for Cr. AFP is highly recommended for the recovery of leached metals from solution even at low concentrations. PMID:26143080

  6. Hydrometallurgical recovery of heavy metals from low grade automobile shredder residue (ASR): An application of advanced Fenton process (AFP).

    PubMed

    Singh, Jiwan; Lee, Byeong-Kyu

    2015-09-15

    To investigate the leaching and recovery of heavy metals from low-grade automobile shredder residue (ASR), the effects of nitric acid (HNO3) and hydrogen peroxide (H2O2) concentrations, liquid/solid (L/S) ratio, leaching temperature and ASR particle size fractions on the heavy metal leaching rate were determined. The heavy metals were recovered by fractional precipitation and advanced Fenton process (AFP) at different pHs. The toxicity characteristic leaching procedure (TCLP) test was also performed in the residue remaining after heavy metal leaching to evaluate the potential toxicity of ASR. The heavy metal leaching efficiency was increased with increasing HNO3 and H2O2 concentrations, L/S ratio and temperature. The heavy metal leaching efficiencies were maximized in the lowest ASR size fraction at 303 K and L/S ratio of 100 mL/g. The kinetic study showed that the metal leaching was best represented by a second-order reaction model, with a value of R(2) > 0.99 for all selected heavy metals. The determined activation energy (kJ/mol) was 21.61, 17.10, 12.15, 34.50, 13.07 and 11.45 for Zn, Fe, Ni, Pb, Cd and Cr, respectively. In the final residue, the concentrations of Cd, Cr and Pb were under their threshold limits in all ASR size fractions. Hydrometallurgical metal recovery was greatly increased by AFP up to 99.96% for Zn, 99.97% for Fe, 95.62% for Ni, 99.62% for Pb, 94.11% for Cd and 96.79% for Cr. AFP is highly recommended for the recovery of leached metals from solution even at low concentrations.

  7. The mesenchymal transcription factor SNAI-1 instructs human liver specification.

    PubMed

    Goldman, Orit; Valdes, Victor Julian; Ezhkova, Elena; Gouon-Evans, Valerie

    2016-07-01

    Epithelial-mesenchymal transition (EMT) and the mesenchymal-epithelial transition (MET) are processes required for embryo organogenesis. Liver develops from the epithelial foregut endoderm from which the liver progenitors, hepatoblasts, are specified. The migrating hepatoblasts acquire a mesenchymal phenotype to form the liver bud. In mid-gestation, hepatoblasts mature into epithelial structures: the hepatocyte cords and biliary ducts. While EMT has been associated with liver bud formation, nothing is known about its contribution to hepatic specification. We previously established an efficient protocol from human embryonic stem cells (hESC) to generate hepatic cells (Hep cells) resembling the hepatoblasts expressing alpha-fetoprotein (AFP) and albumin (ALB). Here we show that Hep cells express both epithelial (EpCAM and E-cadherin) and mesenchymal (vimentin and SNAI-1) markers. Similar epithelial and mesenchymal hepatoblasts were identified in human and mouse fetal livers, suggesting a conserved interspecies phenotype. Knock-down experiments demonstrated the importance of SNAI-1 in Hep cell hepatic specification. Moreover, ChIP assays revealed direct binding of SNAI-1 in the promoters of AFP and ALB genes consistent with its transcriptional activator function in hepatic specification. Altogether, our hESC-derived Hep cell cultures reveal the dual mesenchymal and epithelial phenotype of hepatoblast-like cells and support the unexpected transcriptional activator role of SNAI-1 in hepatic specification. PMID:27240252

  8. KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes

    PubMed Central

    Kim, Sae Won; Yang, Hyun Gul; Kang, Moon Cheol; Lee, Seungwon; Namkoong, Hong; Lee, Seung-Woo; Sung, Young Chul

    2014-01-01

    Identification of novel biomarkers for tumor-initiating cells (TICs) is of critical importance for developing diagnostic and therapeutic strategies against cancers. Here we identified the role of KIAA1114, a full-length translational product of the trophinin gene, as a distinctive marker for TICs in human liver cancer by developing a DNA vaccine-induced monoclonal antibody targeting the putative extracellular domain of KIAA1114. Compared with other established markers of liver TICs, KIAA1114 was unique in that its expression was detected in both alpha fetoprotein (AFP)-positive and AFP-negative hepatocellular carcinoma (HCC) cell lines with the expression levels of KIAA1114 being positively correlated to their tumorigenic potentials. Notably, KIAA1114 expression was strongly detected in primary hepatic tumor, but neither in the adjacent non-tumorous tissue from the same patient nor normal liver tissue. KIAA1114high cells isolated from HCC cell lines displayed TIC-like features with superior functional and phenotypic traits compared to their KIAA1114low counterparts, including tumorigenic abilities in xenotransplantation model, in vitro colony- and spheroid-forming capabilities, expression of stemness-associated genes, and migratory capacity. Our findings not only address the value of a novel antigen, KIAA1114, as a potential diagnostic factor of human liver cancer, but also as an independent biomarker for identifying TIC populations that could be broadly applied to the heterogeneous HCC subtypes. PMID:24713374

  9. Types of Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... stem cells blog from the International Society for Stem Cell Research. Learn About Stem Cells From Lab to You ...

  10. STEM Sell

    ERIC Educational Resources Information Center

    Pantic, Zorica

    2007-01-01

    Between 1994 and 2003, employment in science, technology, engineering and math (STEM) fields grew by a remarkable 23 percent, compared with 17 percent in non-STEM fields, according to federal data. The Bureau of Labor Statistics predicts continued strong growth in STEM job openings through 2014, with emphasis on life sciences, environmental…

  11. Time courses of PIVKA-II and AFP levels after hepatic artery embolization and hepatic artery infusion against hepatocellular carcinoma: relation between the time course and tumor necrosis.

    PubMed

    Kishi, K; Sonomura, T; Mitsuzane, K; Nishida, N; Kimura, M; Satoh, M; Yamada, R; Kodama, N; Kinoshita, M; Tanaka, H

    1992-01-01

    We examined 35 untreated patients with unresectable hepatocellular carcinoma who exhibited positivity for both plasma PIVKA-II and serum AFP, and studied the weekly course of these markers from the pre-TAE or -HAI period to the third week of treatment. We correlated changes in these markers with the tumor necrosis rate and the time course on X-ray CT images. One week after TAE, the tumor necrosis rate and the time course of PIVKA-II showed a significant correlation (r = 0.7), while the correlation was between the time course of AFP and the tumor necrosis rate was insignificant (r = 0.2). At two and three weeks after TAE, both the time course of AFP and PIVKA-II showed significant correlations with the tumor necrosis rate. In 16 patients with tumor necrosis rates of not less than 90%, the mean of the actual half-life (AHL) of PIVKA-II was 3.2 days, the shortest was 1.83 days, and 75% of all AHLs clustered from two days to four days, while the mean and shortest AHLs of AFP were six days and 2.98 days, respectively, exhibiting a broader distribution. On the other hand, in three out of the nine cases of hepatocellular carcinoma complicated with portal tumor thrombi, PIVKA-II increased after HAI in spite of a reduction in tumor size. It was suggested that the PIVKA-II level requires careful interpretation in cases of portal vein obstruction after intensive hepatic arterial infusion of anticancer agents.

  12. JAK2 inhibitor combined with DC-activated AFP-specific T-cells enhances antitumor function in a Fas/FasL signal-independent pathway

    PubMed Central

    Liu, Yang; Wang, Yue-ru; Ding, Guang-hui; Yang, Ting-song; Yao, Le; Hua, Jie; He, Zhi-gang; Qian, Ming-ping

    2016-01-01

    Objective Combination therapy for cancer is more effective than using only standard chemo- or radiotherapy. Our previous results showed that dendritic cell-activated α-fetoprotein (AFP)-specific T-cells inhibit tumor in vitro and in vivo. In this study, we focused on antitumor function of CD8+ T-cells combined with or without JAK2 inhibitor. Methods Proliferation and cell cycle were analyzed by CCK-8 and flow cytometry. Western blot was used to analyze the expression level of related protein and signaling pathway. Results We demonstrated reduced viability and induction of apoptosis of tumor cells with combination treatment. Intriguingly, cell cycle was blocked at the G1 phase by using AFP-specific CD8+ T-cells combined with JAK2 inhibitor (AG490). Furthermore, an enhanced expression of BAX but no influence on Fas/FasL was detected from the tumor cells. Conclusion These results indicate a Fas/FasL-independent pathway for cellular apoptosis in cancer therapies with the treatment of AFP-specific CD8+ T-cells combined with JAK2 inhibitor. PMID:27499636

  13. Hepatoid adenocarcinoma of the gallbladder: a mimicker of hepatocellular carcinoma.

    PubMed

    van den Bos, I C; Hussain, S M; Dwarkasing, R S; Stoop, H; Zondervan, P E; Krestin, G P; de Man, R A

    2007-12-01

    We present a case of a large gallbladder tumour in a patient with no known liver disease and elevated alpha-fetoprotein (AFP), in whom a differential diagnosis from hepatocellular carcinoma (HCC) in a non-cirrhotic liver was particularly difficult given the combination of the size of the tumour, solitary nature, elevated AFP and striking resemblance with HCC at histology. In presenting this patient, we would like to emphasise the role of MRI as a problem-solving tool for analysis of rare tumours of non-hepatocellular origin, including hepatoid adenocarcinoma of the gallbladder. PMID:18065642

  14. Formation of human hepatocyte-like cells with different cellular phenotypes by human umbilical cord blood-derived cells in the human-rat chimeras

    SciTech Connect

    Sun, Yan; Xiao, Dong; Zhang, Ruo-Shuang; Cui, Guang-Hui; Wang, Xin-Hua; Chen, Xi-Gu . E-mail: xiguchen1516@yahoo.com.cn

    2007-06-15

    We took advantage of the proliferative and permissive environment of the developing pre-immune fetus to develop a noninjury human-rat xenograft small animal model, in which the in utero transplantation of low-density mononuclear cells (MNCs) from human umbilical cord blood (hUCB) into fetal rats at 9-11 days of gestation led to the formation of human hepatocyte-like cells (hHLCs) with different cellular phenotypes, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), cytokeratin 19 (CK19), cytokeratin 8 (CK8), cytokeratin 18 (CK18), and albumin (Alb), and with some animals exhibiting levels as high as 10.7% of donor-derived human cells in the recipient liver. More interestingly, donor-derived human cells stained positively for CD34 and CD45 in the liver of 2-month-old rat. Human hepatic differentiation appeared to partially follow the process of hepatic ontogeny, as evidenced by the expression of AFP gene at an early stage and albumin gene at a later stage. Human hepatocytes generated in this model retained functional properties of normal hepatocytes. In this xenogeneic system, the engrafted donor-derived human cells persisted in the recipient liver for at least 6 months after birth. Taken together, these findings suggest that the donor-derived human cells with different cellular phenotypes are found in the recipient liver and hHLCs hold biological activity. This humanized small animal model, which offers an in vivo environment more closely resembling the situations in human, provides an invaluable approach for in vivo investigating human stem cell behaviors, and further in vivo examining fundamental mechanisms controlling human stem cell fates in the future.

  15. STEM Education

    PubMed Central

    Xie, Yu; Fang, Michael; Shauman, Kimberlee

    2015-01-01

    Improving science, technology, engineering, and mathematics (STEM) education, especially for traditionally disadvantaged groups, is widely recognized as pivotal to the U.S.’s long-term economic growth and security. In this article, we review and discuss current research on STEM education in the U.S., drawing on recent research in sociology and related fields. The reviewed literature shows that different social factors affect the two major components of STEM education attainment: (1) attainment of education in general, and (2) attainment of STEM education relative to non-STEM education conditional on educational attainment. Cognitive and social psychological characteristics matter for both major components, as do structural influences at the neighborhood, school, and broader cultural levels. However, while commonly used measures of socioeconomic status (SES) predict the attainment of general education, social psychological factors are more important influences on participation and achievement in STEM versus non-STEM education. Domestically, disparities by family SES, race, and gender persist in STEM education. Internationally, American students lag behind those in some countries with less economic resources. Explanations for group disparities within the U.S. and the mediocre international ranking of US student performance require more research, a task that is best accomplished through interdisciplinary approaches. PMID:26778893

  16. Stem Cell Basics

    MedlinePlus

    ... stem cells? What are the potential uses of human stem cells and the obstacles that must be overcome before ... two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells . ...

  17. Learn About Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... ISSCR Get Involved Media © 2015 International Society for Stem Cell Research Terms of Use Disclaimer Privacy Policy

  18. The three-dimensional solution structure of NaD1, a new floral defensin from Nicotiana alata and its application to a homology model of the crop defense protein alfAFP.

    PubMed

    Lay, Fung T; Schirra, Horst Joachim; Scanlon, Martin J; Anderson, Marilyn A; Craik, David J

    2003-01-01

    NMR spectroscopy and simulated annealing calculations have been used to determine the three-dimensional structure of NaD1, a novel antifungal and insecticidal protein isolated from the flowers of Nicotiana alata. NaD1 is a basic, cysteine-rich protein of 47 residues and is the first example of a plant defensin from flowers to be characterized structurally. Its three-dimensional structure consists of an alpha-helix and a triple-stranded antiparallel beta-sheet that are stabilized by four intramolecular disulfide bonds. NaD1 features all the characteristics of the cysteine-stabilized alphabeta motif that has been described for a variety of proteins of differing functions ranging from antibacterial insect defensins and ion channel-perturbing scorpion toxins to an elicitor of the sweet taste response. The protein is biologically active against insect pests, which makes it a potential candidate for use in crop protection. NaD1 shares 31% sequence identity with alfAFP, an antifungal protein from alfalfa that confers resistance to a fungal pathogen in transgenic potatoes. The structure of NaD1 was used to obtain a homology model of alfAFP, since NaD1 has the highest level of sequence identity with alfAFP of any structurally characterized antifungal defensin. The structures of NaD1 and alfAFP were used in conjunction with structure-activity data for the radish defensin Rs-AFP2 to provide an insight into structure-function relationships. In particular, a putative effector site was identified in the structure of NaD1 and in the corresponding homology model of alfAFP.

  19. Serum copper, ceruloplasmin, protein thiols and thiobarbituric acid reactive substance status in liver cancer associated with elevated levels of alpha-fetoprotein.

    PubMed

    Nayak, Shivananda B; Yashwanth, S; Pinto, Sneha M; Bhat, Vinutha R; Mayya, Srimathi S

    2005-01-01

    Serum copper, ceruloplasmin, protein thiols and thiobarbituric acid reactive substances (TEARS) were estimated in 25 patients of liver cancer. The copper to ceruloplasmin ratio was moderately increased (P<0.05) but the copper (P<0.001) and ceruloplasmin (P<0.001) levels were significantly increased in liver cancer patients when compared to controls. Protein thiols levels were found to be highly significant (P<0.001). Where as the TEARS levels were not found to be significant. Trace elements and free radicals have been implicated in the etiology of cancer. Hence the estimation of ceruloplasmin and protein thiols along with the copper may be of high value in the early diagnosis of cancer.

  20. Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis

    PubMed Central

    Zhang, Hongyu; Siegel, Christopher T.; Shuai, Ling; Lai, Jiejuan; Zeng, Linli; Zhang, Yujun; Lai, Xiangdong; Bie, Ping; Bai, Lianhua

    2016-01-01

    NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2+ cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver, and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 106 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2+ cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2+ cells may be novel adult liver progenitors that participate in liver regeneration. PMID:26905303

  1. STEM Thinking!

    ERIC Educational Resources Information Center

    Reeve, Edward M.

    2015-01-01

    Science, Technology, Engineering, and Mathematics (STEM) is a term seen almost daily in the news. In 2009, President Obama launched the Educate to Innovate initiative to move American students from the middle to the top of the pack in science and math achievement over the next decade (The White House, n.d.). Learning about the attributes of STEM…

  2. Why STEM?

    ERIC Educational Resources Information Center

    Mitts, Charles R.

    2016-01-01

    The International Technology and Engineering Educators Association (ITEEA) defines STEM as a new transdisciplinary subject in schools that integrates the disciplines of science, technology, engineering, and mathematics into a single course of study. There are three major problems with this definition: There is no consensus in support of the ITEEA…

  3. Tandem combination of Trigonella foenum-graecum defensin (Tfgd2) and Raphanus sativus antifungal protein (RsAFP2) generates a more potent antifungal protein.

    PubMed

    Karri, Vasavirama; Bharadwaja, Kirti Pulugurtha

    2013-11-01

    Plant defensins are small (45 to 54 amino acids) positively charged antimicrobial peptides produced by the plant species, which can inhibit the growth of a broad range of fungi at micro-molar concentrations. These basic peptides share a common characteristic three-dimensional folding pattern with one α-helix and three β-sheets that are stabilized by eight disulfide-linked cysteine residues. Instead of using two single-gene constructs, it is beneficial when two effective genes are made into a single fusion gene with one promoter and terminator. In this approach, we have linked two plant defensins namely Trigonella foenum-graecum defensin 2 (Tfgd2) and Raphanus sativus antifungal protein 2 (RsAFP2) genes by a linker peptide sequence (occurring in the seeds of Impatiens balsamina) and made into a single-fusion gene construct. We used pET-32a+ vector system to express Tfgd2-RsAFP2 fusion gene with hexahistidine tag in Escherichia coli BL21 (DE3) pLysS cells. Induction of these cells with 1 mM IPTG achieved expression of the fusion protein. The solubilized His6-tagged recombinant fusion protein was purified by immobilized-metal (Ni2+) affinity column chromatography. The final yield of the fusion protein was 500 ng/μL. This method produced biologically active recombinant His6-tagged fusion protein, which exhibited potent antifungal action towards the plant pathogenic fungi (Botrytis cinerea, Fusarium moniliforme, Fusarium oxysporum, Phaeoisariopsis personata and Rhizoctonia solani along with an oomycete pathogen Phytophthora parasitica var nicotianae) at lower concentrations under in vitro conditions. This strategy of combining activity of two defensin genes into a single-fusion gene will definitely be a promising utility for biotechnological applications. PMID:24022215

  4. Tandem combination of Trigonella foenum-graecum defensin (Tfgd2) and Raphanus sativus antifungal protein (RsAFP2) generates a more potent antifungal protein.

    PubMed

    Karri, Vasavirama; Bharadwaja, Kirti Pulugurtha

    2013-11-01

    Plant defensins are small (45 to 54 amino acids) positively charged antimicrobial peptides produced by the plant species, which can inhibit the growth of a broad range of fungi at micro-molar concentrations. These basic peptides share a common characteristic three-dimensional folding pattern with one α-helix and three β-sheets that are stabilized by eight disulfide-linked cysteine residues. Instead of using two single-gene constructs, it is beneficial when two effective genes are made into a single fusion gene with one promoter and terminator. In this approach, we have linked two plant defensins namely Trigonella foenum-graecum defensin 2 (Tfgd2) and Raphanus sativus antifungal protein 2 (RsAFP2) genes by a linker peptide sequence (occurring in the seeds of Impatiens balsamina) and made into a single-fusion gene construct. We used pET-32a+ vector system to express Tfgd2-RsAFP2 fusion gene with hexahistidine tag in Escherichia coli BL21 (DE3) pLysS cells. Induction of these cells with 1 mM IPTG achieved expression of the fusion protein. The solubilized His6-tagged recombinant fusion protein was purified by immobilized-metal (Ni2+) affinity column chromatography. The final yield of the fusion protein was 500 ng/μL. This method produced biologically active recombinant His6-tagged fusion protein, which exhibited potent antifungal action towards the plant pathogenic fungi (Botrytis cinerea, Fusarium moniliforme, Fusarium oxysporum, Phaeoisariopsis personata and Rhizoctonia solani along with an oomycete pathogen Phytophthora parasitica var nicotianae) at lower concentrations under in vitro conditions. This strategy of combining activity of two defensin genes into a single-fusion gene will definitely be a promising utility for biotechnological applications.

  5. Three Independent Techniques Localize Expression of Transcript afp-11 and Its Bioactive Peptide Products to the Paired AVK Neurons in Ascaris suum: In Situ Hybridization, Immunocytochemistry, and Single Cell Mass Spectrometry

    PubMed Central

    2012-01-01

    We utilized three independent techniques, immunocytochemistry (ICC), single cell mass spectrometry (MS), and in situ hybridization (ISH), to localize neuropeptides and their transcripts in the nervous system of the nematode Ascaris suum. AF11 (SDIGISEPNFLRFa) is an endogenous peptide with potent paralytic effects on A. suum locomotory behavior. A highly specific antibody to AF11 showed robust immunostaining for AF11 in the paired AVK neurons in the ventral ganglion. We traced the processes from the AVK neurons into the ventral nerve cord and identified them as ventral cord interneurons. MS and MS/MS of single dissected AVKs detected AF11, two previously characterized peptides (AF25 and AF26), seven novel sequence-related peptides, including several sharing a PNFLRFamide C-terminus, and peptide NY, a peptide with an unrelated sequence. Also present in a subset of AVKs was AF2, a peptide encoded by the afp-4 transcript. By sequencing the afp-11 transcript, we discovered that it encodes AF11, all the AF11-related peptides detected by MS in AVK, and peptide NY. ISH detected the afp-11 transcript in AVK neurons, consistent with other techniques. ISH did not detect afp-11 in the ALA neuron, although both ICC and MS found AF11 in ca. 30% of ALAs. All 10 AF11-related peptides reduced acetylcholine-induced muscle contraction, but they differed in their rate of reversal of inhibition after removal of the peptide. PMID:23509978

  6. Three independent techniques localize expression of transcript afp-11 and its bioactive peptide products to the paired AVK neurons in Ascaris suum: in situ hybridization, immunocytochemistry, and single cell mass spectrometry.

    PubMed

    Jarecki, Jessica L; Viola, India R; Andersen, Kari M; Miller, Andrew H; Ramaker, Megan A; Vestling, Martha M; Stretton, Antony O

    2013-03-20

    We utilized three independent techniques, immunocytochemistry (ICC), single cell mass spectrometry (MS), and in situ hybridization (ISH), to localize neuropeptides and their transcripts in the nervous system of the nematode Ascaris suum . AF11 (SDIGISEPNFLRFa) is an endogenous peptide with potent paralytic effects on A. suum locomotory behavior. A highly specific antibody to AF11 showed robust immunostaining for AF11 in the paired AVK neurons in the ventral ganglion. We traced the processes from the AVK neurons into the ventral nerve cord and identified them as ventral cord interneurons. MS and MS/MS of single dissected AVKs detected AF11, two previously characterized peptides (AF25 and AF26), seven novel sequence-related peptides, including several sharing a PNFLRFamide C-terminus, and peptide NY, a peptide with an unrelated sequence. Also present in a subset of AVKs was AF2, a peptide encoded by the afp-4 transcript. By sequencing the afp-11 transcript, we discovered that it encodes AF11, all the AF11-related peptides detected by MS in AVK, and peptide NY. ISH detected the afp-11 transcript in AVK neurons, consistent with other techniques. ISH did not detect afp-11 in the ALA neuron, although both ICC and MS found AF11 in ca. 30% of ALAs. All 10 AF11-related peptides reduced acetylcholine-induced muscle contraction, but they differed in their rate of reversal of inhibition after removal of the peptide.

  7. Gender impact on first trimester markers in Down syndrome screening.

    PubMed

    Larsen, Severin Olesen; Wøjdemann, Karen R; Shalmi, Anne-Cathrine; Sundberg, Karin; Christiansen, Michael; Tabor, Ann

    2002-12-01

    The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male fetuses. PMID:12478634

  8. Stem Cell Sciences plc.

    PubMed

    Daniels, Sebnem

    2006-09-01

    Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

  9. Sensitive electrochemical immunosensor based on three-dimensional nanostructure gold electrode.

    PubMed

    Zhong, Guangxian; Lan, Ruilong; Zhang, Wenxin; Fu, Feihuan; Sun, Yiming; Peng, Huaping; Chen, Tianbin; Cai, Yishan; Liu, Ailin; Lin, Jianhua; Lin, Xinhua

    2015-01-01

    A sensitive electrochemical immunosensor was developed for detection of alpha-fetoprotein (AFP) based on a three-dimensional nanostructure gold electrode using a facile, rapid, "green" square-wave oxidation-reduction cycle technique. The resulting three-dimensional gold nanocomposites were characterized by scanning electron microscopy and cyclic voltammetry. A "sandwich-type" detection strategy using an electrochemical immunosensor was employed. Under optimal conditions, a good linear relationship between the current response signal and the AFP concentrations was observed in the range of 10-50 ng/mL with a detection limit of 3 pg/mL. This new immunosensor showed a fast amperometric response and high sensitivity and selectivity. It was successfully used to determine AFP in a human serum sample with a relative standard deviation of <5% (n=5). The proposed immunosensor represents a significant step toward practical application in clinical diagnosis and monitoring of prognosis.

  10. Sensitive electrochemical immunosensor based on three-dimensional nanostructure gold electrode

    PubMed Central

    Zhong, Guangxian; Lan, Ruilong; Zhang, Wenxin; Fu, Feihuan; Sun, Yiming; Peng, Huaping; Chen, Tianbin; Cai, Yishan; Liu, Ailin; Lin, Jianhua; Lin, Xinhua

    2015-01-01

    A sensitive electrochemical immunosensor was developed for detection of alpha-fetoprotein (AFP) based on a three-dimensional nanostructure gold electrode using a facile, rapid, “green” square-wave oxidation-reduction cycle technique. The resulting three-dimensional gold nanocomposites were characterized by scanning electron microscopy and cyclic voltammetry. A “sandwich-type” detection strategy using an electrochemical immunosensor was employed. Under optimal conditions, a good linear relationship between the current response signal and the AFP concentrations was observed in the range of 10–50 ng/mL with a detection limit of 3 pg/mL. This new immunosensor showed a fast amperometric response and high sensitivity and selectivity. It was successfully used to determine AFP in a human serum sample with a relative standard deviation of <5% (n=5). The proposed immunosensor represents a significant step toward practical application in clinical diagnosis and monitoring of prognosis. PMID:25834434

  11. Human embryonic stem cell proliferation and differentiation as parameters to evaluate developmental toxicity.

    PubMed

    Pal, Rajarshi; Mamidi, Murali Krishna; Das, Anjan Kumar; Bhonde, Ramesh

    2011-06-01

    In vitro models based on embryonic stem cells (ESC) are highly promising for improvement of predictive toxicology screening in humans. After the successful validation of embryonic stem cell test (EST) in 2001; concerns have been raised on the usage of mouse ESC and also the morphological evaluation of beating cell clusters. This requires specialized skill-sets and is highly prone to misjudgement and false positive results. To overcome these limitations, we undertook the present study incorporating improvisations over the conventional EST. Here, we explored the potential of a human ESC (hESC)-based assay to evaluate the potential toxicity of penicillin-G, caffeine, and hydroxyurea. Drug treatment inhibited hESC adhesion and substantially altered the morphology and viability (∼ 50%) of embryoid bodies (EBs). Flow cytometry analysis not only showed a significant increase of apoptotic cells in the highest doses but also induced a diverse pattern in DNA content and cell cycle distribution relative to control. Both semi-quantitative and quantitative RT-PCR studies revealed a selective down regulation of markers associated with stemness (Nanog, Rex1, SOX-2, and hTERT); cardiac mesoderm (Cripto1, MEF-2C, and Brachyury); hepatic endoderm (AFP, HNF-3β, HNF-4α, GATA-4, and SOX-17); and neuroectoderm (Nestin, SOX-1, NURR1, NEFH, Synaptophysin, TH, and Olig2) in a drug as well as dose dependent manner indicating abnormal differentiation. Furthermore, a decrease in the expression of AFP and GFAP proteins followed by a dose-dependent reduction in the levels of hCG-β, progesterone-II, and estradiol hormones was demonstrated by immunocytochemistry and ECLIA, respectively. This new and unique approach comprising of DNA cell cycle analysis, germ layer-specific marker expression and hormone levels as endpoints might offer a clinically relevant and commercially viable alternative for predicting in vivo developmental toxicity. PMID:20945368

  12. Antioxidant and ACE-inhibitory activities of hemp (Cannabis sativa L.) protein hydrolysates produced by the proteases AFP, HT, Pro-G, actinidin and zingibain.

    PubMed

    Teh, Sue-Siang; Bekhit, Alaa El-Din A; Carne, Alan; Birch, John

    2016-07-15

    Hemp protein isolates (HPIs) were hydrolysed by proteases (AFP, HT, ProG, actinidin and zingibain). The enzymatic hydrolysis of HPIs was evaluated through the degree of hydrolysis and SDS-PAGE profiles. The bioactive properties of the resultant hydrolysates (HPHs) were accessed through ORAC, DPPḢ scavenging and ACE-inhibitory activities. The physical properties of the resultant HPHs were evaluated for their particle sizes, zeta potential and surface hydrophobicity. HT had the highest rate of caseinolytic activity at the lowest concentration (0.1 mg mL(-1)) compared to other proteases that required concentration of 100 mg mL(-1) to achieve their maximum rate of caseinolytic activity. This led to the highest degree of hydrolysis of HPIs by HT in the SDS-PAGE profiles. Among all proteases and substrates, HT resulted in the highest bioactivities (ORAC, DPPḢ scavenging and ACE-inhibitory activities) generated from alkali extracted HPI in the shortest time (2 h) compared to the other protease preparations.

  13. Antioxidant and ACE-inhibitory activities of hemp (Cannabis sativa L.) protein hydrolysates produced by the proteases AFP, HT, Pro-G, actinidin and zingibain.

    PubMed

    Teh, Sue-Siang; Bekhit, Alaa El-Din A; Carne, Alan; Birch, John

    2016-07-15

    Hemp protein isolates (HPIs) were hydrolysed by proteases (AFP, HT, ProG, actinidin and zingibain). The enzymatic hydrolysis of HPIs was evaluated through the degree of hydrolysis and SDS-PAGE profiles. The bioactive properties of the resultant hydrolysates (HPHs) were accessed through ORAC, DPPḢ scavenging and ACE-inhibitory activities. The physical properties of the resultant HPHs were evaluated for their particle sizes, zeta potential and surface hydrophobicity. HT had the highest rate of caseinolytic activity at the lowest concentration (0.1 mg mL(-1)) compared to other proteases that required concentration of 100 mg mL(-1) to achieve their maximum rate of caseinolytic activity. This led to the highest degree of hydrolysis of HPIs by HT in the SDS-PAGE profiles. Among all proteases and substrates, HT resulted in the highest bioactivities (ORAC, DPPḢ scavenging and ACE-inhibitory activities) generated from alkali extracted HPI in the shortest time (2 h) compared to the other protease preparations. PMID:26948606

  14. Differentiation of bone mesenchymal stem cells into hepatocyte-like cells induced by liver tissue homogenate.

    PubMed

    Xing, X K; Feng, H G; Yuan, Z Q

    2016-01-01

    This study investigated the efficacy and feasibility of inducing the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into hepatocyte-like cells in vitro using Sprague Dawley rats, as a model of hepatocyte generation for cell transplantation. BMSCs were isolated and grown using the adherent method and exposed to 5 or 10% liver tissue homogenate, before being collected for analysis after 0, 7, 14, and 21 days. Immunofluorescence and western blotting were employed to detect the liver-specific markers a-fetoprotein (AFP) and albumin (ALB). Supernatant urea content was also measured to verify that differentiation had been induced. After 7 days in the presence of 10% liver tissue homogenate, BMSCs demonstrated hepatocyte-like morphological characteristics, and with prolonged culture time, liver-specific markers were gradually produced at levels indicating cell maturation. AFP expression peaked at 14 days then began to decrease, while both urea and ALB levels increased with induction time. Overall, marker expression in the 5% homogenate group was less than or equal to the 10% group at each time point. Thus, in a rat model, liver tissue homogenate obtained from partial hepatectomy can induce the differentiation of BMSCs into hepatocyte-like cells. This method is simple, feasible, and has remarkable real-world application potential. PMID:27525848

  15. Serum levels of CA15-3, AFP, CA19-9 and CEA tumor markers in cancer care and treatment of patients with impaired renal function on hemodialysis.

    PubMed

    Estakhri, Rasoul; Ghahramanzade, Ali; Vahedi, Amir; Nourazarian, Alireza

    2013-01-01

    Since renal failure causes decrease in tumor marker excretion, use of these markers in cancer care and treatment in patients with renal insufficiency or hemodialysis is controversial. The aim of this study was to investigate differences of serum levels of tumor markers CA15-3, AFP, CA19-9 and CEA in patients with impaired renal function. A total of 100 patients referred to the Tabriz Immam Reza and Amiralmomenin hospital from June 2010 to November 2011 were selected for study. Subjects were divided to 3 groups of healthy, dialysis and renal failure but non hemodialysis cases, the last category being re-grouped based on creatinine clearance. No significant relationship between different groups in serum levels of CEA (P=0.99) and CA19-9 (P=0.29) tumor markers was found. A significant correlation was observed between serum levels of AFP (P<0.001) and CA15-3 (P<0.001) and also a tendency between creatinine clearance and CEA (r=0.05, P=0.625). Creatinine clearance significantly correlated with AFP (P<0.001, r=0.53) and CA15-3 (p=0.00, r=-0.412), but not CA19-9 (P=0.089, r=-0.171). According to results of this study it appears that use of tumor markers in patients with impaired renal function should be performed with special precautions.

  16. Rotatable stem and lock

    DOEpatents

    Deveney, J.E.; Sanderson, S.N.

    1981-10-27

    A valve stem and lock is disclosed which includes a housing surrounding a valve stem, a solenoid affixed to an interior wall of the housing, an armature affixed to the valve stem and a locking device for coupling the armature to the housing body. When the solenoid is energized, the solenoid moves away from the housing body, permitting rotation of the valve stem.

  17. Rotatable stem and lock

    DOEpatents

    Deveney, Joseph E.; Sanderson, Stephen N.

    1984-01-01

    A valve stem and lock include a housing surrounding a valve stem, a solenoid affixed to an interior wall of the housing, an armature affixed to the valve stem and a locking device for coupling the armature to the housing body. When the solenoid is energized, the solenoid moves away from the housing body, permitting rotation of the valve stem.

  18. Stem cell biobanks.

    PubMed

    Bardelli, Silvana

    2010-04-01

    Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment. PMID:20560026

  19. Stem cells supporting other stem cells

    PubMed Central

    Leatherman, Judith

    2013-01-01

    Adult stem cell therapies are increasingly prevalent for the treatment of damaged or diseased tissues, but most of the improvements observed to date are attributed to the ability of stem cells to produce paracrine factors that have a trophic effect on existing tissue cells, improving their functional capacity. It is now clear that this ability to produce trophic factors is a normal and necessary function for some stem cell populations. In vivo adult stem cells are thought to self-renew due to local signals from the microenvironment where they live, the niche. Several niches have now been identified which harbor multiple stem cell populations. In three of these niches – the Drosophila testis, the bulge of the mammalian hair follicle, and the mammalian bone marrow – one type of stem cell has been found to produce factors that contribute to the maintenance of a second stem cell population in the shared niche. In this review, I will examine the architecture of these three niches and discuss the molecular signals involved. Together, these examples establish a new paradigm for stem cell behavior, that stem cells can promote the maintenance of other stem cells. PMID:24348512

  20. Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts.

    PubMed

    Martin-Padura, Ines; Marighetti, Paola; Agliano, Alice; Colombo, Federico; Larzabal, Leyre; Redrado, Miriam; Bleau, Anne-Marie; Prior, Celia; Bertolini, Francesco; Calvo, Alfonso

    2012-07-01

    Hepatocellular carcinoma (HCC) is the fifth most common solid tumor and the third leading cause of cancer-related deaths. Currently available chemotherapeutic options are not curative due in part to tumor resistance to conventional therapies. We generated orthotopic HCC mouse models in immunodeficient NOD/SCID/IL2rγ null mice by injection of human alpha-feto protein (hAFP)- and/or luciferase-expressing HCC cell lines and primary cells from patients, where tumor growth and spread can be accurately monitored in a non-invasive way. In this model, low-dose metronomic administration of cyclophosphamide (LDM-CTX) caused complete regression of the tumor mass. A significant increase in survival (P<0.0001), reduced aberrant angiogenesis and hyperproliferation, and decrease in the number of circulating tumor cells were found in LDM-CTX-treated animals, in comparison with untreated mice. Co-administration of LDM-CTX with anti-VEGF therapy further improved the therapeutic efficacy. However, the presence of residual circulating hAFP levels suggested that some tumor cells were still present in livers of treated mice. Immunohistochemistry revealed that those cells had a hAFP+/CD13+/PCNA- phenotype, suggesting that they were dormant cancer stem cells (CSC). Indeed, discontinuation of therapy resulted in tumor regrowth. Moreover, in-vitro LDM-CTX treatment reduced hepatosphere formation in both number and size, and the resulting spheres were enriched in CD13+ cells indicating that these cells were particularly resistant to therapy. Co-treatment of the CD13-targeting drug, bestatin, with LDM-CTX leads to slower tumor growth and a decreased tumor volume. Therefore, combining a CD13 inhibitor, which targets the CSC-like population, with LDM-CTX chemotherapy may be used to eradicate minimal residual disease and improve the treatment of liver cancer. PMID:22546866

  1. Information on Stem Cell Research

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS Information on Stem Cell Research Research @ NINDS Stem Cell Highlights Submit a hESC ... found here: Human Induced Pluripotent Stem Cells NINDS Stem Cell Research on Campus The Intramural Research Program of NINDS ...

  2. STEM Club Participation and STEM Schooling Outcomes

    ERIC Educational Resources Information Center

    Gottfried, Michael A.; Williams, Darryl N.

    2013-01-01

    To develop a more robust understanding of the relationship between non-formal, school-based STEM activities and students' success and persistence in STEM fields, this study evaluates how math club participation influences math GPA and how science club participation influences science GPA. Additionally, this study evaluates how math or science club…

  3. Stem Cell Research.

    PubMed

    Trounson, Alan; Kolaja, Kyle; Petersen, Thomas; Weber, Klaus; McVean, Maralee; Funk, Kathleen A

    2015-01-01

    Stem cells have great potential in basic research and are being slowly integrated into toxicological research. This symposium provided an overview of the state of the field, stem cell models, described allogenic stem cell treatments and issues of immunogenicity associated with protein therapeutics, and tehn concentrated on stem cell uses in regenerative medicine focusing on lung and testing strategies on engineered tissues from a pathologist's perspective.

  4. Understanding STEM: Current Perceptions

    ERIC Educational Resources Information Center

    Brown, Ryan; Brown, Joshua; Reardon, Kristin; Merrill, Chris

    2011-01-01

    In many ways, the push for STEM (science, technology, engineering, and mathematics) education appears to have grown from a concern for the low number of future professionals to fill STEM jobs and careers and economic and educational competitiveness. The proponents of STEM education believe that by increasing math and science requirements in…

  5. Hepatic differentiation of human embryonic stem cells as microscaled multilayered colonies leading to enhanced homogeneity and maturation.

    PubMed

    Yao, Rui; Wang, Jingyu; Li, Xiaokang; Jung Jung, Da; Qi, Hao; Kee, Keh Kooi; Du, Yanan

    2014-11-12

    Directed differentiation of human embryonic stem cells (hESCs) towards hepatocyte-like cells on planar tissue culture plates has been extensively investigated with great promise to provide alternative cell sources for drug metabolism/toxicity testing. Recently, hepatic differentiation of hESCs in 3D configuration with better mimicry of embryonic liver development represents incremental efforts to improve the differentiation efficiency and cellular maturation. However, most of the present 3D differentiation configurations involved interruptive operations during the multi-staged differentiation process, which might impose unwanted influence on cellular differentiation. Most of the current researches resulted in generation of hepatocytes with high expression of AFP, which is minimally expressed in primary hepatocytes. Here, off-the-shelf micro-stencil arrays are developed to generate adherent multilayered colonies composed of hESCs-derived cells. Uninterrupted cellular differentiation and proliferation is achieved to recapitulate the continuous and multi-stage liver development. Compared with conventional 2D format, the micro-scaled multilayered colonies with uniform and defined sizes constrained within the microwells are composed of more homogenous and mature hepatocyte-like cells with significantly lowered AFP expression and elevated hepatic functions. The multilayered colonies as novel 3D configuration for hepatic differentiation of hESCs represent a significant step toward efficient generation of functional hepatocytes for regenerative medicine and drug discovery. PMID:25059765

  6. Umbilical cord-derived mesenchymal stem cells inhibit growth and promote apoptosis of HepG2 cells.

    PubMed

    Tang, Ying-Mei; Bao, Wei-Min; Yang, Jin-Hui; Ma, Lin-Kun; Yang, Jing; Xu, Ying; Yang, Li-Hong; Sha, Feng; Xu, Zhi-Yuan; Wu, Hua-Mei; Zhou, Wei; Li, Yan; Li, Yu-Hua

    2016-09-01

    Hepatocellular carcinoma is the fifth most common type of cancer worldwide and remains difficult to treat. The aim of this study was to investigate the effects of mesenchymal stem cells (MSCs) derived from the umbilical cord (UC‑MSCs) on HepG2 hepatocellular carcinoma cells. UC‑MSCs were co‑cultured with HepG2 cells and biomarkers of UC‑MSCs were analyzed by flow cytometry. mRNA and protein expression of genes were determined by reverse transcription‑polymerase chain reaction and flow cytometry, respectively. Passage three and seven UC‑MSCs expressed CD29, CD44, CD90 and CD105, whereas CD34 and CD45 were absent on these cells. Co‑culture with UC‑MSCs inhibited proliferation and promoted apoptosis of HepG2 cells in a time‑dependent manner. The initial seeding density of UC‑MSCs also influenced the proliferation and apoptosis of HepG2 cells, with an increased number of UC‑MSCs causing enhanced proliferation inhibition and cell apoptosis. Co‑culture with UC‑MSCs downregulated mRNA and protein expression of α‑fetoprotein (AFP), Bcl‑2 and Survivin in HepG2 cells. Thus, UC‑MSCs may inhibit growth and promote apoptosis of HepG2 cells through downregulation of AFP, Bcl‑2 and Survivin. US-MSCs may be used as a novel therapy for treating hepatocellular carcinoma in the future. PMID:27485485

  7. Upregulation of MiR-122 via Trichostatin A Treatments in Hepatocyte-like Cells Derived from Mesenchymal Stem Cells.

    PubMed

    Alizadeh, Effat; Eslaminejad, MohamadReza Baghaban; Akbarzadeh, Abolfazl; Sadeghi, Zohre; Abasi, Mozghan; Herizchi, Roya; Zarghami, Nosratollah

    2016-02-01

    The miR-122 is a tissue-specific miRNA; its expression is abundant in liver. MiR-122 upregulation is crucial for differentiation, functionality, and maintenance of differentiated phenotype in hepatocytes. The improving effects of trichostatin A (TSA) on hepatic differentiation have been reported previously. The aim of this study was to determine whether TSA can affect the expression of miR-122 in hepatocyte-like cells (HLCs) generated from human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). The hepatic differentiation of hAT-MSCs induced by a mixture of growth factors and cytokines either with or without TSA treatments. The functionality of HLCs generated with or without TSA and the expression levels of miR-122 were studied. The expression levels of miR-122 in TSA-treated HLCs was significantly (p < 0.05) higher than those generated by growth factors and cytokines, only. The downregulation of a-fetoprotein (AFP) levels but enhanced albumin synthesis (p < 0.05) and upregulation of liver-enriched transcription factors (LETFs) HNF4α (hepatocyte nuclear factor 4α) and HNF6 (hepatocyte nuclear factor 6) were observed in TSA-treated HLCs (p < 0.05). In conclusion, administration of TSA in hepatogenic differentiation of hAT-MSCs resulted in higher expression levels of miR-122, facilitation of differentiation, and subsequently attenuation of AFP levels.

  8. Tumor Markers for Hepatocellular Carcinoma: Simple and Significant Predictors of Outcome in Patients with HCC

    PubMed Central

    Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Sone, Yasuhiro; Kaneoka, Yuji; Maeda, Atsuyuki

    2015-01-01

    Background The effectiveness of tumor markers in evaluating outcomes of patients with hepatocellular carcinoma (HCC) remains to be clarified. Summary The usefulness of the HCC tumor markers, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), and des-gamma-carboxy prothrombin (DCP) was reviewed. Elevations in these tumor markers at the time of HCC diagnosis correlate with disease progression as assessed by both imaging studies and pathologic examinations. The combination of these three tumor markers results in good predictive ability for patient survival after diagnosis. In addition, combination at the time of HCC diagnosis of these three tumor markers (as a measure of tumor progression) and serum albumin and bilirubin levels (as indicators of remnant liver function) can be used for HCC staging and further predicts prognosis in patients with HCC. Key Message The prognosis of patients with HCC can be well discriminated based solely on serum markers. Staging of HCC with serum markers is objective; if stored serum samples are available, HCC stages can be standardized across different countries and time periods. PMID:26020034

  9. Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients with Advanced Hepatitis C

    PubMed Central

    Sterling, Richard K.; Wright, Elizabeth C.; Morgan, Timothy R.; Seeff, Leonard B.; Hoefs, John C.; Di Bisceglie, Adrian M.; Dienstag, Jules L.; Lok, Anna S.

    2013-01-01

    Background Prospective studies of serum HCC biomarkers in patients with advanced hepatitis C are lacking. Aims To determine frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. Methods Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. Results 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20-199, while 2.3% had at least one AFP value ≥200 ng/mL; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90-149, and 14.7% had at least one DCP value ≥150 mAU/mL. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP >20 ng/mL. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/mL had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/mL had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. Conclusions Mild-moderate elevations in total AFP and DCP but not AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. PMID:21931376

  10. Plant stem cell niches.

    PubMed

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  11. Artificial Stem Cell Niches

    PubMed Central

    Lutolf, Matthias P.; Blau, Helen M.

    2011-01-01

    Stem cells are characterized by their dual ability to reproduce themselves (self-renew) and specialize (differentiate), yielding a plethora of daughter cells that maintain and regenerate tissues. In contrast to their embryonic counterparts, adult stem cells retain their unique functions only if they are in intimate contact with an instructive microenvironment, termed stem cell niche. In these niches, stem cells integrate a complex array of molecular signals that, in concert with induced cell-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such “artificial niches” constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration. PMID:20882496

  12. Investigating Preservice STEM Teacher Conceptions of STEM Education

    ERIC Educational Resources Information Center

    Radloff, Jeff; Guzey, Selcen

    2016-01-01

    Surrounding the national emphasis on improving STEM education, effective STEM educators are required. Connected, yet often overlooked, is the need for effective preservice STEM teaching instruction for incoming educators. At a basic level, preservice STEM teacher education should include STEM content, pedagogy, and conceptualization. However, the…

  13. Liver Rapid Reference Set Application: Hemken - Abbott (2015) — EDRN Public Portal

    Cancer.gov

    The aim for this testing is to find a small panel of biomarkers (n=2-5) that can be tested on the Abbott ARCHITECT automated immunoassay platform for the early detection of hepatocellular carcinoma (HCC). This panel of biomarkers should perform significantly better than alpha-fetoprotein (AFP) alone based on multivariate statistical analysis. This testing of the EDRN reference set will help expedite the selection of a small panel of ARCHITECT biomarkers for the early detection of HCC. The panel of ARCHITECT biomarkers Abbott plans to test include: AFP, protein induced by vitamin K absence or antagonist-II (PIVKA-II), golgi protein 73 (GP73), hepatocellular growth factor (HGF), dipeptidyl peptidase 4 (DPP4) and DPP4/seprase (surface expressed protease) heterodimer hybrid. PIVKA-II is abnormal des-carboxylated prothrombin (DCP) present in vitamin K deficiency.

  14. [Complete Resection of Non-seminomatous Germ Cell Tumor with Plastron Approach].

    PubMed

    Suzuki, Jun; Oizumi, Hiroyuki; Kato, Hirohisa; Endoh, Makoto; Watarai, Hikaru; Hamada, Akira; Suzuki, Katsuyuki; Nakahashi, Kenta; Sasage, Takayuki; Sadahiro, Mitsuaki

    2016-07-01

    A 17-year-old man was admitted to our hospital for the abnormal chest shadow. Chest computed tomography(CT) demonstrated mediastinal tumor, measuring 13 cm in diameter with high serum level of alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG). The lesions were diagnosed as mixed germ cell tumors including a non-seminomatous malignant component by CT guided needle biopsy. After 5 courses of chemotherapy, the serum AFP and hCG were decreased almost normal level but the tumor size was not changed. Because it seemed to be difficult to get sufficient operating field with standard median sternotomy and patient wanted to treat funnel chest, we selected tumor resection with plastron approach. The tumor was completely resected with a good operation field by this procedure. PMID:27365059

  15. Plasma Circulating Cell-free DNA Integrity as a Promising Biomarker for Diagnosis and Surveillance in Patients with Hepatocellular Carcinoma

    PubMed Central

    Huang, Ao; Zhang, Xin; Zhou, Shao-Lai; Cao, Ya; Huang, Xiao-Wu; Fan, Jia; Yang, Xin-Rong; Zhou, Jian

    2016-01-01

    The clinical significance of circulating cell-free DNA (cfDNA) integrity as diagnostic and surveillance biomarker in hepatocellular carcinoma (HCC) was investigated and compared to that of alpha fetoprotein (AFP). Liver cancer patients had lower cfDNA integrity than those with benign diseases (P = 0.0167) and healthy individuals (P = 0.0025). Patients with HCC and non-HCC liver cancers (P = 0.7356), and patients with benign diseases and healthy individuals (P = 0.9138) had comparable cfDNA integrity respectively. cfDNA integrity increased after hepatectomy in cancer patients (P = 0.0003). The AUCs for detecting HCC by cfDNA integrity and AFP were 0.705 (P = 0.005) and 0.605 (P = 0.156), respectively. We found cfDNA integrity decreased in HCC patients and has the potential as promising biomarker for HCC diagnosis and treatment surveillance.

  16. Liver cancer immunoassay with magnetic nanoparticles and MgO-based magnetic tunnel junction sensors

    NASA Astrophysics Data System (ADS)

    Lei, Z. Q.; Li, L.; Li, G. J.; Leung, C. W.; Shi, J.; Wong, C. M.; Lo, K. C.; Chan, W. K.; Mak, C. S. K.; Chan, S. B.; Chan, N. M. M.; Leung, C. H.; Lai, P. T.; Pong, P. W. T.

    2012-04-01

    We have demonstrated the detection of alpha-fetoprotein (AFP) labeled with magnetic nanoparticles (MNPs) using MgO-based magnetic tunnel junction (MTJ) sensors. AFP is an important hepatic tumor biomarker and the detection of AFP has significant applications for clinical diagnostics and immunoassay for early-stage liver cancer indications. In this work, MgO-based MTJ sensors and 20-nm iron-oxide magnetic nanoparticles (MNPs) were used for detecting AFP antigens by a sandwich-assay configuration. The MTJ sensors with a sensing area of 4 × 2 μm2 possess tunneling magnetoresistance (TMR) of 122% and sensitivity of 0.95%/Oe at room temperature. The target AFP antigens of three concentrations were successfully detected, and the experimental data indicate that the resistance variations of the MTJ sensor increased with the AFP concentration ratios proportionally. These results demonstrate that MgO-based MTJ sensors together with MNPs are a promising biosensing platform for liver cancer immunoassay.

  17. Automated support-resolution strategy for a one-way chemiluminescent multiplex immunoassay.

    PubMed

    Yang, Zhanjun; Liu, Hong; Zong, Chen; Yan, Feng; Ju, Huangxian

    2009-07-01

    An automated support-resolution strategy was designed to couple with a flow-through immunosensing system for performing a one-way chemiluminescent (CL) multiplex immunoassay. Different from multilabel and multichannel-based detection techniques, this immunoassay method employed a single horseradish peroxidase (HRP) label in one way. With the use of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as model analytes, the capture antibodies for CEA and AFP were immobilized on the inner wall of a glass tube and the surface of paramagnetic microspheres (PMs), respectively. The on-line incubation could be performed in the glass tube after introducing the mixture of CEA, HRP-labeled anti-CEA antibody, AFP, anti-AFP immobilized PMs, and HRP-labeled anti-AFP antibody. With the use of a wash step, the formed sandwich immunocomplexes were separated automatically and the immunocomplex immobilized PMs were captured in another unmodified glass tube with a magnet. The CL signals from the two glass tubes were near-simultaneously collected with the aid of an optical shutter to perform quantitative detection. CEA and AFP could be rapidly assayed in the ranges of 1.0-60 and 1.0-80 ng/mL within 27 min. The assay results of clinical serum samples with the proposed method were in an acceptable agreement with the reference values. This system provides a promising multiplex immunoassay approach for clinical applications.

  18. Global Collaborative STEM Education

    NASA Astrophysics Data System (ADS)

    Meabh Kelly, Susan; Smith, Walter

    2016-04-01

    Global Collaborative STEM Education, as the name suggests, simultaneously supports two sets of knowledge and skills. The first set is STEM -- science, technology, engineering and math. The other set of content knowledge and skills is that of global collaboration. Successful global partnerships require awareness of one's own culture, the biases embedded within that culture, as well as developing awareness of the collaborators' culture. Workforce skills fostered include open-mindedness, perseverance when faced with obstacles, and resourceful use of technological "bridges" to facilitate and sustain communication. In respect for the 2016 GIFT Workshop focus, Global Collaborative STEM Education projects dedicated to astronomy research will be presented. The projects represent different benchmarks within the Global Collaborative STEM Education continuum, culminating in an astronomy research experience that fully reflects how the global STEM workforce collaborates. To facilitate wider engagement in Global Collaborative STEM Education, project summaries, classroom resources and contact information for established international collaborative astronomy research projects will be disseminated.

  19. Stem cells and reproduction

    PubMed Central

    Du, Hongling; Taylor, Hugh S.

    2011-01-01

    Purpose of review To review the latest developments in reproductive tract stem cell biology. Recent findings In 2004, two studies indicated that ovaries contain stem cells which form oocytes in adults and that can be cultured in vitro into mature oocytes. A live birth after orthotopic transplantation of cyropreserved ovarian tissue in a woman whose ovaries were damaged by chemotherapy demonstrates the clinical potential of these cells. In the same year, another study provided novel evidence of endometrial regeneration by stem cells in women who received bone marrow transplants. This finding has potential for the use in treatment of uterine disorders. It also supports a new theory for the cause of endometriosis, which may have its origin in ectopic transdifferentiation of stem cells. Several recent studies have demonstrated that fetal cells enter the maternal circulation and generate microchimerism in the mother. The uterus is a dynamic organ permeable to fetal stem cells, capable of transdifferentiation and an end organ in which bone marrow stem cells may differentiate. Finally stem cell transformation can be an underlying cause of ovarian cancer. Summary Whereas we are just beginning to understand stem cells, the potential implications of stem cells to reproductive biology and medicine are apparent. PMID:20305558

  20. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  1. Stem cells in dermatology.

    PubMed

    Ogliari, Karolyn Sassi; Marinowic, Daniel; Brum, Dario Eduardo; Loth, Fabrizio

    2014-01-01

    Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today.

  2. STEM Careers Ambassadors

    ERIC Educational Resources Information Center

    Eaton, Denise

    2011-01-01

    This article is designed to help teachers feel more confident in their work with STEM Ambassadors to further enhance enrichment activities. Skills shortages in Science, Technology, Engineering, Maths (STEM) and the Built Environment are well documented, and will continue to be an issue whether people are in a period of recession or recovery. The…

  3. Stem cells in urology.

    PubMed

    Aboushwareb, Tamer; Atala, Anthony

    2008-11-01

    The shortage of donors for organ transplantation has stimulated research on stem cells as a potential resource for cell-based therapy in all human tissues. Stem cells have been used for regenerative medicine applications in many organ systems, including the genitourinary system. The potential applications for stem cell therapy have, however, been restricted by the ethical issues associated with embryonic stem cell research. Instead, scientists have explored other cell sources, including progenitor and stem cells derived from adult tissues and stem cells derived from the amniotic fluid and placenta. In addition, novel techniques for generating stem cells in the laboratory are being developed. These techniques include somatic cell nuclear transfer, in which the nucleus of an adult somatic cell is placed into an oocyte, and reprogramming of adult cells to induce stem-cell-like behavior. Such techniques are now being used in tissue engineering applications, and some of the most successful experiments have been in the field of urology. Techniques to regenerate bladder tissue have reached the clinic, and exciting progress is being made in other areas, such as regeneration of the kidney and urethra. Cell therapy as a treatment for incontinence and infertility might soon become a reality. Physicians should be optimistic that regenerative medicine and tissue engineering will one day provide mainstream treatment options for urologic disorders.

  4. Making STEM Connections

    ERIC Educational Resources Information Center

    Stump, Sheryl L.; Bryan, Joel A.; McConnell, Tom J.

    2016-01-01

    Integrated approaches to education in science, technology, engineering, and mathematics (STEM), especially those set in the context of real-world situations, can motivate and deepen students' learning of the STEM subjects (National Academy of Engineering and National Research Council 2014). This article describes two integrated investigations used…

  5. Teaching STEM by Design

    ERIC Educational Resources Information Center

    Billiar, Kristen; Hubelbank, Jeanne; Oliva, Thomas; Camesano, Terri

    2014-01-01

    Developing innovative science, technology, engineering and mathematics (STEM) curricula that elicit student excitement for learning is a continuous challenge for K-12 STEM teachers. Generating these lessons while meeting conflicting pedagogical objectives and constraints of time, content, and cost from various parties is truly a challenging task…

  6. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies.

  7. Bringing STEM to Life

    ERIC Educational Resources Information Center

    Berkeihiser, Mike; Ray, Dori

    2013-01-01

    The interdisciplinary approach that science, technology, engineering and mathematics (STEM) projects inspire in both teachers and students "brings to light a larger picture that promotes real-world scientific applications, which has in turn been shown to increase undergraduate persistence in STEM." The high school students have been warned…

  8. STEM School Discourse Patterns

    ERIC Educational Resources Information Center

    Tofel-Grehl, Colby; Callahan, Carolyn M.

    2016-01-01

    Analysis of discursive practices in science classrooms within STEM schools may provide meaningful information about the nature of these classrooms and, potentially, their uniqueness. Full descriptions of current practice can serve as a foundation for exploring the differences in instructional norms within STEM specialized schools and across…

  9. Lock For Valve Stem

    NASA Technical Reports Server (NTRS)

    Burley, Richard K.; Guirguis, Kamal S.

    1991-01-01

    Simple, cheap device locks valve stem so its setting cannot be changed by unauthorized people. Device covers valve stem; cover locked in place with standard padlock. Valve lock made of PVC pipe and packing band. Shears, drill or punch, and forming rod only tools needed.

  10. Designing for STEM Integration

    ERIC Educational Resources Information Center

    Berland, Leema K.

    2013-01-01

    We are increasingly seeing an emphasis on STEM integration in high school classrooms such that students will learn and apply relevant math and science content while simultaneously developing engineering habits of mind. However, research in both science education and engineering education suggests that this goal of truly integrating STEM is rife…

  11. Investigating Preservice STEM Teacher Conceptions of STEM Education

    NASA Astrophysics Data System (ADS)

    Radloff, Jeff; Guzey, Selcen

    2016-10-01

    Surrounding the national emphasis on improving STEM education, effective STEM educators are required. Connected, yet often overlooked, is the need for effective preservice STEM teaching instruction for incoming educators. At a basic level, preservice STEM teacher education should include STEM content, pedagogy, and conceptualization. However, the literature suggests no leading conception of STEM education, and little is known about how preservice STEM teachers are conceptualizing STEM education. In order to explore preservice STEM teacher conceptions of STEM education, preservice teachers at a large, Midwestern research university were given an open-ended survey eliciting both textual and visual responses. Here, we report and discuss the results of employing this instrument in relation with the current STEM conceptualization literature.

  12. Investigating Preservice STEM Teacher Conceptions of STEM Education

    NASA Astrophysics Data System (ADS)

    Radloff, Jeff; Guzey, Selcen

    2016-07-01

    Surrounding the national emphasis on improving STEM education, effective STEM educators are required. Connected, yet often overlooked, is the need for effective preservice STEM teaching instruction for incoming educators. At a basic level, preservice STEM teacher education should include STEM content, pedagogy, and conceptualization. However, the literature suggests no leading conception of STEM education, and little is known about how preservice STEM teachers are conceptualizing STEM education. In order to explore preservice STEM teacher conceptions of STEM education, preservice teachers at a large, Midwestern research university were given an open-ended survey eliciting both textual and visual responses. Here, we report and discuss the results of employing this instrument in relation with the current STEM conceptualization literature.

  13. Intraoperative Stem Cell Therapy

    PubMed Central

    Coelho, Mónica Beato; Cabral, Joaquim M.S.; Karp, Jeffrey M.

    2013-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium. PMID:22809140

  14. Expanding STEM Education | Poster

    Cancer.gov

    Editor’s note: This article is written as a reflection on experiential STEM education by a student who completed her Werner H. Kirsten internship in June 2015. Here, she advocates for incorporating hands-on experience into STEM curricula. If the only way for high school students to learn science, technology, engineering, and mathematics (STEM) is through textbooks, then count me out. But how then do you get students to learn STEM outside of the classroom? The focus of this article is to advocate for high school STEM education through experiential learning. Tom Freston, one of the founders and the chief executive officer (CEO) of MTV Productions, said in an interview in Men’s Journal that “innovation is taking two things that already exist and...

  15. Biphasic modulation of Wnt signaling supports efficient foregut endoderm formation from human pluripotent stem cells.

    PubMed

    Hoepfner, Jeannine; Kleinsorge, Mandy; Papp, Oliver; Ackermann, Mania; Alfken, Susanne; Rinas, Ursula; Solodenko, Wladimir; Kirschning, Andreas; Sgodda, Malte; Cantz, Tobias

    2016-05-01

    Pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) are of great promise in regenerative medicine, including molecular studies of disease mechanisms, if the affected cell type can be authentically generated during in vitro differentiation. Most existing protocols aim to mimic embryonic development steps by the supplementation of specific cytokines and small molecules, but the involved signaling pathways need further exploration. In this study, we investigated enhanced initial activation of Wnt signaling for definitive endoderm formation and subsequent rapid shutdown of Wnt signaling for proper foregut endoderm specification using 3 μM CHIR99021 and 0.5 μg/mL of secreted frizzled-related protein 5 (sFRP-5) for biphasic modulation of the Wnt pathway. The definitive endoderm and foregut endoderm differentiation capabilities of Wnt pathway-modulated cells were determined based on the expression levels of the endodermal transcription factors SOX17 and FOXA2 and those of the transcription activator GATA4 and the α-fetoprotein (AFP) gene, respectively. Furthermore, the resulting biphasic Wnt pathway modulation was investigated at the protein level by analyzing phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and β-catenin. Finally, Wnt target gene expression was determined using an improved lentiviral reporter construct that enabled robust T-cell transcription factor 4 (TCF4)/lymphoid enhancer-binding factor 1 (LEF1)-mediated luciferase expression in differentiating pluripotent stem cells. In conclusion, we demonstrated robust, homogeneous, and efficient derivation of foregut endodermal cells by inducing a biphasic modulation of the Wnt signaling pathway. PMID:26861571

  16. Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM) and alpha-L-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma.

    PubMed

    Mossad, Nehad A; Mahmoud, Enas H; Osman, Enas A; Mahmoud, Sherif H; Shousha, Hend I

    2014-11-01

    Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha-fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP may be elevated with cirrhosis in the absence of HCC. Serum alpha-L-fucosidase (AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM) were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40 patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM and AFU levels were significantly elevated in HCC group compared to cirrhotic group (P value<0.001 and <0.001, respectively). Receiver operating characteristic curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity 87.5% and specificity 66% and for AFU was 25 U/L with sensitivity 87.5% and specificity 98%. AFP cutoff value was 48 ng/mL with sensitivity of 70% and specificity of 53.3%. The simultaneous determination of AFP and SCCA-IgM activity increased the sensitivity to 92.5% and specificity to 62.1%. There were positive significant correlations between SCCA-IgM and each of AFU (r=0.296, P=0.005) and AFP (r=0.284, P=0.007) and no correlation between AFP and AFU. All markers did not correlate with the tumor size or affected by the Child score. The significant difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients suggests their use as potential diagnostic tools and allows identifying a new group of HCC patients even in the absence of elevated AFP. PMID:25129443

  17. Fish stem cell cultures.

    PubMed

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-04-13

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on "Fish Stem Cells and Nuclear Transfer", we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer.

  18. Autophagy in stem cells

    PubMed Central

    Guan, Jun-Lin; Simon, Anna Katharina; Prescott, Mark; Menendez, Javier A.; Liu, Fei; Wang, Fen; Wang, Chenran; Wolvetang, Ernst; Vazquez-Martin, Alejandro; Zhang, Jue

    2013-01-01

    Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future. PMID:23486312

  19. Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma

    PubMed Central

    Song, Pei-Pei; Xia, Ju-Feng; Inagaki, Yoshinori; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Kokudo, Norihiro; Tang, Wei

    2016-01-01

    The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice. PMID:26755875

  20. Genome-wide analysis of DNA methylation in hepatoblastoma tissues

    PubMed Central

    Cui, Ximao; Liu, Baihui; Zheng, Shan; Dong, Kuiran; Dong, Rui

    2016-01-01

    DNA methylation has a crucial role in cancer biology. In the present study, a genome-wide analysis of DNA methylation in hepatoblastoma (HB) tissues was performed to verify differential methylation levels between HB and normal tissues. As alpha-fetoprotein (AFP) has a critical role in HB, AFP methylation levels were also detected using pyrosequencing. Normal and HB liver tissue samples (frozen tissue) were obtained from patients with HB. Genome-wide analysis of DNA methylation in these tissues was performed using an Infinium HumanMethylation450 BeadChip, and the results were confirmed with reverse transcription-quantitative polymerase chain reaction. The Infinium HumanMethylation450 BeadChip demonstrated distinctively less methylation in HB tissues than in non-tumor tissues. In addition, methylation enrichment was observed in positions near the transcription start site of AFP, which exhibited lower methylation levels in HB tissues than in non-tumor liver tissues. Lastly, a significant negative correlation was observed between AFP messenger RNA expression and DNA methylation percentage, using linear Pearson's R correlation coefficients. The present results demonstrate differential methylation levels between HB and normal tissues, and imply that aberrant methylation of AFP in HB could reflect HB development. Expansion of these findings could provide useful insight into HB biology. PMID:27446465

  1. The Predictive Power of Serum α-Fetoprotein and Des-γ-Carboxy Prothrombin for Survival Varies by Tumor Size in Hepatocellular Carcinoma.

    PubMed

    Tsugawa, Daisuke; Fukumoto, Takumi; Kido, Masahiro; Takebe, Atsushi; Tanaka, Motofumi; Kuramitsu, Kaori; Matsumoto, Ippei; Ajiki, Tetsuo; Koyama, Tatsuki; Ku, Yonson

    2016-01-01

    Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are frequently used as tumor markers in hepatocellular carcinoma (HCC). The authors hypothesized different patient populations with varying tumor sizes would influence the predictive power of tumor markers for survival in HCC patients. The authors investigated the influence of tumor size on predictive powers of AFP and DCP. 181 patients underwent hepatectomy for HCC from 2003 to 2008 at Kobe University Hospital. Tumor markers were measured before and at 1 month post-hepatectomy. The Cox proportional-hazards model revealed that preoperative serum AFP was associated with survival; its effects depended on tumor size. Hazard ratios (HRs) for preoperative AFP were maximum for medium-sized HCC, and for DCP, HRs were maximum in small-sized tumors. Post-hepatectomy, both tumor markers were associated with survival, revealing significant interactions with tumor size. HRs for postoperative AFP were greater than 1 for relatively wide range tumors (3-11 cm). HRs for postoperative DCP increased with tumor size, with a strong prognostic predictive power for tumors >5 cm. The predictive power of serum tumor markers varied by tumor size in HCC patients. By selecting the appropriate tumor marker, its predictive power can be improved. PMID:27363395

  2. Innovation and STEM Schools

    ERIC Educational Resources Information Center

    Roberts, Julia Link

    2015-01-01

    How do schools with a focus on science, technology, engineering, and mathematics (STEM) fit in with state goals to increase innovation and to boost the economy? This article briefly discusses how educators can encourage creativity and innovation.

  3. Stem Cell Information: Glossary

    MedlinePlus

    ... based therapies Cell culture Cell division Chromosome Clone Cloning Cord blood stem cells Culture medium Differentiation Directed ... Pluripotent Polar body Preimplantation Proliferation Regenerative medicine Reproductive cloning Signals Somatic cell Somatic cell nuclear transfer (SCNT) ...

  4. Exploring the STEM shortage

    NASA Astrophysics Data System (ADS)

    Gates, S. James, Jr.; Bhulai, Alfred; IcePilot; JoeB

    2014-12-01

    In reply to Margaret Harris' article on "The STEM shortage paradox" (Graduate careers, October pp56-59, http://ow.ly/DXvIq) and a related post on the physicsworld.com blog ("The STEM employment paradox, revisited", http://ow.ly/DXvCl), both of which questioned reports that the UK is suffering from a severe shortage of graduates in science, technology, engineering and mathematics.

  5. Plant Stem Cells.

    PubMed

    Greb, Thomas; Lohmann, Jan U

    2016-09-12

    Among the trending topics in the life sciences, stem cells have received a fair share of attention in the public debate - mostly in connection with their potential for biomedical application and therapies. While the promise of organ regeneration and the end of cancer have captured our imagination, it has gone almost unnoticed that plant stem cells represent the ultimate origin of much of the food we eat, the oxygen we breathe, as well the fuels we burn. Thus, plant stem cells may be ranked among the most important cells for human well-being. Research by many labs in the last decades has uncovered a set of independent stem cell systems that fulfill the specialized needs of plant development and growth in four dimensions. Surprisingly, the cellular and molecular design of these systems is remarkably similar, even across diverse species. In some long-lived plants, such as trees, plant stem cells remain active over hundreds or even thousands of years, revealing the exquisite precision in the underlying control of proliferation, self-renewal and differentiation. In this minireview, we introduce the basic features of the three major plant stem cell systems building on these facts, highlight their modular design at the level of cellular layout and regulatory underpinnings and briefly compare them with their animal counterparts. PMID:27623267

  6. Chemotherapy targeting cancer stem cells.

    PubMed

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future.

  7. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  8. Valve stem and packing assembly

    DOEpatents

    Wordin, John J.

    1991-01-01

    A valve stem and packing assembly is provided in which a rotatable valve stem includes a first tractrix surface for sliding contact with a stem packing and also includes a second tractrix surface for sliding contact with a bonnet. Force is applied by means of a spring, gland flange, and gland on the stem packing so the stem packing seals to the valve stem and bonnet. This configuration serves to create and maintain a reliable seal between the stem packing and the valve stem. The bonnet includes a second complementary tractrix surface for contacting the second sliding tractrix surface, the combination serving as a journal bearing for the entire valve stem and packing assembly. The journal bearing so configured is known as a Schiele's pivot. The Schiele's pivot also serves to maintain proper alignment of the valve stem with respect to the bonnet. Vertical wear between the surfaces of the Schiele's pivot is uniform at all points of contact between the second sliding tractrix surface and the second complementary tractrix surface of a bonnet. The valve stem is connected to a valve plug by means of a slip joint. The valve is opened and closed by rotating the valve stem. The slip joint compensates for wear on the Schiele's pivot and on the valve plug. A ledge is provided on the valve bonnet for the retaining nut to bear against. The ledge prevents overtightening of the retaining nut and the resulting excessive friction between stem and stem packing.

  9. Valve stem and packing assembly

    DOEpatents

    Wordin, J.J.

    1991-09-03

    A valve stem and packing assembly is provided in which a rotatable valve stem includes a first tractrix surface for sliding contact with a stem packing and also includes a second tractrix surface for sliding contact with a bonnet. Force is applied by means of a spring, gland flange, and gland on the stem packing so the stem packing seals to the valve stem and bonnet. This configuration serves to create and maintain a reliable seal between the stem packing and the valve stem. The bonnet includes a second complementary tractrix surface for contacting the second sliding tractrix surface, the combination serving as a journal bearing for the entire valve stem and packing assembly. The journal bearing so configured is known as a Schiele's pivot. The Schiele's pivot also serves to maintain proper alignment of the valve stem with respect to the bonnet. Vertical wear between the surfaces of the Schiele's pivot is uniform at all points of contact between the second sliding tractrix surface and the second complementary tractrix surface of a bonnet. The valve stem is connected to a valve plug by means of a slip joint. The valve is opened and closed by rotating the valve stem. The slip joint compensates for wear on the Schiele's pivot and on the valve plug. A ledge is provided on the valve bonnet for the retaining nut to bear against. The ledge prevents over tightening of the retaining nut and the resulting excessive friction between stem and stem packing. 2 figures.

  10. Expression of biomarker genes of differentiation in D3 mouse embryonic stem cells after exposure to different embryotoxicant and non-embryotoxicant model chemicals

    PubMed Central

    Romero, Andrea C.; del Río, Eva; Vilanova, Eugenio; Sogorb, Miguel A.

    2015-01-01

    There is a necessity to develop in vitro methods for testing embryotoxicity (Romero et al., 2015) [1]. We studied the progress of D3 mouse embryonic stem cells differentiation exposed to model embryotoxicants and non-embryotoxicants chemicals through the expression of biomarker genes. We studied a set of 16 different genes biomarkers of general cellular processes (Cdk1, Myc, Jun, Mixl, Cer and Wnt3), ectoderm formation (Nrcam, Nes, Shh and Pnpla6), mesoderm formation (Mesp1, Vegfa, Myo1e and Hdac7) and endoderm formation (Flk1 and Afp). We offer dose response in order to derive the concentration causing either 50% or 200% of expression of the biomarker gene. These records revealed to be a valuable end-point to predict in vitro the embryotoxicity of chemicals (Romero et al., 2015) [1]. PMID:26568980

  11. 5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE, LOOKING NORTHWEST - High Mountain Dams in Upalco Unit, Drift Lake Dam, Ashley National Forest, 11.4 miles Northwest of Swift Creek Campground, Mountain Home, Duchesne County, UT

  12. 5. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE (28' WIDE HARDESTY CAST IRON SLIDE HEADGATE), LOOKING NORTHEAST - High Mountain Dams in Bonneville Unit, Duck Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  13. 5. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE, (12' DIAMETER HARDESTY MODEL 112 CIRCULAR GATE), LOOKING NORTHEAST - High Mountain Dams in Bonneville Unit, Island Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  14. 5. VIEW OF UPRIGHT OUTLET GATE, STEM, STEM GUIDE AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF UPRIGHT OUTLET GATE, STEM, STEM GUIDE AND WHEEL (10' HARDESTY CAST IRON VERTICAL LIFT GATE), LOOKING WEST - High Mountain Dams in Bonneville Unit, Weir Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  15. 4. VIEW OF INCLINED OUTLET GATE, STEM, STEM GUIDE AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VIEW OF INCLINED OUTLET GATE, STEM, STEM GUIDE AND WHEEL (10' HARDESTY VERTICAL LIFT GATE), LOOKING NORTHWEST - High Mountain Dams in Bonneville Unit, Pot Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  16. 6. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE (18' HARDESTY GATE), LOOKING SOUTHEAST - High Mountain Dams in Bonneville Unit, Long Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  17. 7. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE (15' HARDESTY MODEL 115 GATE), LOOKING NORTHWEST - High Mountain Dams in Bonneville Unit, Marjorie Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  18. 7. VIEW OF UPRIGHT OUTLET GATE, WHEEL STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. VIEW OF UPRIGHT OUTLET GATE, WHEEL STEM AND STEM GUIDE (14' DIAMETER CIRCULAR CALCO CAST IRON SLIDE GATE), LOOKING SOUTHEAST - High Mountain Dams in Bonneville Unit, Fire Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  19. 5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE (HARDESTY CAST IRON RECTANGULAR SLIDE GATE), LOOKING SOUTHWEST - High Mountain Dams in Bonneville Unit, Lost Lake Dam, Kamas, Summit County, UT

  20. Diagnostic value of serum Golgi protein 73 for HBV-related primary hepatic carcinoma

    PubMed Central

    Gao, Guosheng; Dong, Feibo; Xu, Xiaozhen; Hu, Airong; Hu, Yaoren

    2015-01-01

    Background: Alpha-fetoprotein (AFP) levels are routinely used for diagnosis and monitoring of hepatic diseases, but it has a limited value. Golgi protein 73 (GP73) has been suggested as a new marker for hepatic diseases. Objective: To explore the clinical value of serum GP73 in different diseases associated with hepatitis B virus (HBV) infection. Method: Between January 2010 and August 2014, serum samples from 88 patients with chronic hepatitis B (CHB), 78 patients with HBV-related liver cirrhosis (LC), and 194 patients with HBV-related primary hepatic cancer (PHC) were collected. Serum samples from 30 healthy volunteers were used as controls. ELISA and microparticle enzyme immunoassay were used to measure serum GP73 and AFP levels. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of serum GP73 and AFP for PHC. Results: For the diagnosis of PHC, GP73 showed a sensitivity of 65.5% and specificity of 66.3%, while AFP levels showed sensitivity of 64.4% and specificity of 76.5%. Serial testing (both tests are positive) could increase the specificity (sensitivity of 45.9% and specificity of 85.5%) while parallel testing (any single positive test result) could increase the sensitivity (sensitivity of 84.0% and specificity of 57.2%). Serum GP73 and AFP levels were significantly different between Child-Pugh grades (P<0.001 for GP73 and P=0.044 for AFP). Significant differences in serum GP73 and AFP were found between TNM stages (all P<0.001). Conclusion: Serum GP73 had limited diagnostic value for HBV-related PHC. The combined use of serum GP73 and AFP levels improved the diagnostic efficacy. PMID:26617863

  1. Simultaneous quantitative detection of multiple tumor markers with a rapid and sensitive multicolor quantum dots based immunochromatographic test strip.

    PubMed

    Wang, Chunying; Hou, Fei; Ma, Yicai

    2015-06-15

    A novel multicolor quantum dots (QDs) based immunochromatographic test strip (ICTS) was developed for simultaneous quantitative detection of multiple tumor markers, by utilizing alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) as models. The immunosensor could realize simultaneous quantitative detection of tumor markers with only one test line and one control line on the nitrocellulose membrane (NC membrane) due to the introduction of multicolor QDs. In this method, a mixture of mouse anti-AFP McAb and mouse anti-CEA McAb was coated on NC membrane as test line and goat anti-mouse IgG antibody was coated as control line. Anti-AFP McAb-QDs546 conjugates and anti-CEA McAb-QDs620 conjugates were mixed and applied to the conjugate pad. Simultaneous quantitative detection of multiple tumor markers was achieved by detecting the fluorescence intensity of captured QDs labels on test line and control line using a test strip reader. Under the optimum conditions, AFP and CEA could be detected as low as 3 ng/mL and 2 ng/mL in 15 min with a sample volume of 80 μL, and no obvious cross-reactivity was observed. The immunosensor was validated with 130 clinical samples and in which it exhibited high sensitivity (93% for AFP and 87% for CEA) and specificity (94% for AFP and 97% for CEA). The immunosensor also demonstrated high recoveries (87.5-113% for AFP and 90-97.3% for CEA) and low relative standard deviations (RSDs) (2.8-6.2% for AFP and 4.9-9.6% for CEA) when testing spiked human serum. This novel multicolor QDs based ICTS provides an easy and rapid, simultaneous quantitative detecting strategy for point-of-care testing of tumor markers. PMID:25562743

  2. Augmenting the antitumor effect of TRAIL by SOCS3 with double-regulated replicating oncolytic adenovirus in hepatocellular carcinoma.

    PubMed

    Wei, Rui-Cheng; Cao, Xin; Gui, Jing-Hua; Zhou, Xiu-Mei; Zhong, Dan; Yan, Qiao-Lin; Huang, Wei-Dan; Qian, Qi-Jun; Zhao, Feng-Li; Liu, Xin-Yuan

    2011-09-01

    Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was successfully constructed. Two therapeutic genes, suppressor of cytokine signaling 3 (SOCS3) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were chosen and incorporated into this vector system, respectively. The combined treatment of AFP-D55-SOCS3 and AFP-D55-TRAIL (2:3 ratio) exhibited potent antitumor activity in AFP-positive HCC cell lines compared with any other treatment both in vitro and in vivo. Specific replication and low progeny yield in AFP-positive HCC cell lines rendered these double-regulated oncolytic adenoviruses remarkably safe. Our data demonstrated that restoration of SOCS3, which inhibits the JAK/STAT3 pathway, by AFP-D55-SOCS3 not only could antagonize HCC therapeutic resistance to TRAIL and adenoviruses, but could also induce cell cycle arrest in HCC cell lines. SOCS3 could down-regulate Cyclin D1 and anti-apoptotic proteins such as XIAP, Survivin, Bcl-xL, and Mcl-1, which are responsible for the synergistic inhibitory effects of AFP-D55-SOCS3 and AFP-D55-TRAIL. Dual gene and double-regulated oncolytic adenoviruses may provide safety and excellent antitumor effects for liver cancer, which is the advantage of a cancer-targeting gene virotherapy strategy. PMID:21361790

  3. [Stem cells and cancer].

    PubMed

    Arvelo, Francisco; Cotte, Carlos; Sojo, Felipe

    2014-12-01

    Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Cancer stem cells are a subpopulation of the cells that form the tumor. The discovery of these human cancer cells opens a perspective for understanding tumor recurrence, drug resistance and metastasis; and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Therapeutic alternatives emerge from a better understanding of the biology and the environment of tumor stem cells. The present paper aims to summarize the characteristics and properties of cancer stem cells, the ongoing research, as well as the best strategies for prevention and control of the mechanisms of tumor recurrence.

  4. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  5. Catalyzing stem cell research.

    PubMed

    Willemse, Lisa; Lyall, Drew; Rudnicki, Michael

    2008-09-01

    In 2001, the Stem Cell Network was the first of its kind, a bold initiative to forge and nurture pan-Canadian collaborations involving researchers, engineers, clinicians and private and public sector partners. Canada's broad and deep pool of stem cell talent proved to be a fertile ground for such an initiative, giving rise to a strong, thriving network that, 7 years later, can list innovative cell expansion and screening technologies, early-phase clinical trials for stroke, pulmonary hypertension, muscular dystrophy and cornea replacement, and leading discourse on ethical, legal and social issues among its accomplishments. As it moves into its second and final phase of funding, the Stem Cell Network continues to push boundaries and has set its sights on overcoming the obstacles that impede the transfer of research findings to clinical applications, commercial products and public policy. PMID:18729799

  6. Aneuploidy in stem cells

    PubMed Central

    Garcia-Martinez, Jorge; Bakker, Bjorn; Schukken, Klaske M; Simon, Judith E; Foijer, Floris

    2016-01-01

    Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to reality. However, as somatic cells might have accumulated various chromosomal abnormalities, including aneuploidies throughout their lives, the resulting IPSCs might no longer carry the perfect blueprint for the tissue to be generated, or worse, become at risk of adopting a malignant fate. In this review, we discuss the contribution of aneuploidy to healthy tissues and how aneuploidy can lead to disease. Furthermore, we review the differences between how somatic cells and stem cells respond to aneuploidy. PMID:27354891

  7. Catalyzing stem cell research.

    PubMed

    Willemse, Lisa; Lyall, Drew; Rudnicki, Michael

    2008-09-01

    In 2001, the Stem Cell Network was the first of its kind, a bold initiative to forge and nurture pan-Canadian collaborations involving researchers, engineers, clinicians and private and public sector partners. Canada's broad and deep pool of stem cell talent proved to be a fertile ground for such an initiative, giving rise to a strong, thriving network that, 7 years later, can list innovative cell expansion and screening technologies, early-phase clinical trials for stroke, pulmonary hypertension, muscular dystrophy and cornea replacement, and leading discourse on ethical, legal and social issues among its accomplishments. As it moves into its second and final phase of funding, the Stem Cell Network continues to push boundaries and has set its sights on overcoming the obstacles that impede the transfer of research findings to clinical applications, commercial products and public policy.

  8. STEM on the radio

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2011-10-01

    Looking for an Internet radio station focusing on programing about science, technology, engineering, and math (STEM)? The U.S. National Science Foundation (NSF) announced on 26 September the launch of Science360 Radio, which it says is the first Internet radio stream dedicated to STEM programing. Science360 includes more than 100 radio shows and podcasts that are available on the Web as well as on iPhone and Android devices. The shows originate from a variety of sources, including NSF, other U.S. government agencies, science organizations, universities, and media outlets. For more information, see http://science360.gov/files/.

  9. Laser biomodulation on stem cells

    NASA Astrophysics Data System (ADS)

    Liu, Timon C.; Duan, Rui; Li, Yan; Li, Xue-Feng; Tan, Li-Ling; Liu, Songhao

    2001-08-01

    Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.

  10. STEM--Beyond the Acronym

    ERIC Educational Resources Information Center

    Vasquez, Jo Anne

    2015-01-01

    When most educators think of STEM education, they think of fully integrated projects seamlessly combining all four disciplines--science, technology, engineering, and mathematics. Although such transdisciplinary STEM units are ideal, writes Vasquez, they are not the only way to give students valuable STEM experiences. She gives examples of two…

  11. Cold Hardening in Citrus Stems

    PubMed Central

    Yelenosky, George

    1975-01-01

    Stem cold hardening developed to different levels in citrus types tested in controlled environments. Exotherms indicated ice spread was more uniform and rapid in unhardened than in cold-hardened stems. All attempts to inhibit the functioning of citrus leaves resulted in less cold hardening in the stems. Citrus leaves contribute a major portion of cold hardening in the wood. PMID:16659340

  12. Stem cells in microfluidics

    PubMed Central

    Wu, Huei-Wen; Lin, Chun-Che; Lee, Gwo-Bin

    2011-01-01

    Microfluidic techniques have been recently developed for cell-based assays. In microfluidic systems, the objective is for these microenvironments to mimic in vivo surroundings. With advantageous characteristics such as optical transparency and the capability for automating protocols, different types of cells can be cultured, screened, and monitored in real time to systematically investigate their morphology and functions under well-controlled microenvironments in response to various stimuli. Recently, the study of stem cells using microfluidic platforms has attracted considerable interest. Even though stem cells have been studied extensively using bench-top systems, an understanding of their behavior in in vivo-like microenvironments which stimulate cell proliferation and differentiation is still lacking. In this paper, recent cell studies using microfluidic systems are first introduced. The various miniature systems for cell culture, sorting and isolation, and stimulation are then systematically reviewed. The main focus of this review is on papers published in recent years studying stem cells by using microfluidic technology. This review aims to provide experts in microfluidics an overview of various microfluidic systems for stem cell research. PMID:21522491

  13. STEMMING the Gap

    ERIC Educational Resources Information Center

    Kahler, Jim; Valentine, Nancy

    2011-01-01

    America has a gap when it comes to youth pursuing science and technology careers. In an effort to improve the knowledge and application of science, technology, engineering, and math (STEM), after-school programs can work in conjunction with formal in-school curriculum to improve science education. One organization that actively addresses this…

  14. Helping STEM Take Root

    ERIC Educational Resources Information Center

    Schachter, Ron

    2011-01-01

    STEM--the catchy shorthand for "science, technology, engineering and mathematics"--has been part of the school improvement discussion for more than a decade, as educational leaders and policy makers have underscored the importance of these areas in preparing students for an internationally competitive, 21st-century economy. But while the acronym…

  15. Helping STEM Take Root

    ERIC Educational Resources Information Center

    Schachter, Ron

    2011-01-01

    STEM--shorthand for "science, technology, engineering, and mathematics"--has been part of the school improvement discussion for more than a decade, as educational leaders and policy makers have underscored the importance of these areas in an internationally competitive, 21st-century economy. But building and implementing programs that emphasize…

  16. A Problem with STEM

    ERIC Educational Resources Information Center

    Marder, Michael

    2013-01-01

    Striking differences between physics and biology have important implications for interdisciplinary science, technology, engineering, and mathematics (STEM) education. The author is a physicist with interdisciplinary connections. The research group in which he works, the Center for Nonlinear Dynamics at the University of Texas at Austin, is…

  17. SMOOTH MUSCLE STEM CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well-studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, includ...

  18. STEM Sense and Nonsense

    ERIC Educational Resources Information Center

    Charette, Robert N.

    2015-01-01

    If you can believe the daily flood of mass media stories, journal articles, and white papers, the United States is facing a STEM worker crisis. Business leaders and politicians warn that the nation is falling hopelessly behind in the global economic race because our students are unprepared for and uninterested in science, technology, engineering,…

  19. "Excellence" in STEM Education

    ERIC Educational Resources Information Center

    Clark, Aaron C.

    2012-01-01

    So what does it take to achieve excellence in STEM education? That is the title of the author's presentation delivered at International Technology and Engineering Educators Association's (ITEEA's) FTEE "Spirit of Excellence" Breakfast on March 16, 2012, in Long Beach, California. In preparation for this presentation, the author went back and read…

  20. Equivalency of buffalo (Bubalus bubalis) embryonic stem cells derived from fertilized, parthenogenetic, and hand-made cloned embryos.

    PubMed

    Muzaffar, Musharifa; Selokar, Naresh L; Singh, Karn P; Zandi, Mohammad; Singh, Manoj K; Shah, Riaz A; Chauhan, Manmohan S; Singla, Suresh K; Palta, Prabhat; Manik, Radheysham

    2012-06-01

    This study was aimed at establishing buffalo embryonic stem cells (ESCs) from in vitro fertilized (IVF), parthenogenetic, and hand-made cloned (HMC) embryos and to check their equivalency in terms of stem cell marker expression, longevity, proliferation, and differentiation pattern. ESCs derived from all three sources were found by immunofluorescence to express the pluripotency markers SSEA-4, TRA-1-60, TRA-1-81, OCT4, and SOX2 and were able to form embryoid bodies containing cells expressing genes specific to endoderm (AFP, HNF4, and GATA4), mesoderm (MSX1, BMP4, and ASA), and ectoderm (cytokeratin 8 and NF68). Reverse transcriptase PCR (RT-PCR) showed cells from all sources to be positive for pluripotency markers OCT4, SOX2, NANOG, STAT3, REX1, FOXD3, NUCLEOSTEMIN, and TELOMERASE. Pluripotency markers OCT4, SOX2, NANOG, and c-MYC were also analyzed by real-time PCR. No significant differences were observed among ESCs from all three sources for all these genes except NANOG, whose expression was higher (p<0.05) in HMC-derived ESCs (6.897±2.3) compared to that in parthenogenesis- and IVF-derived cells (1.603±0.315 and 1±0, respectively). Pluripotent, stable buffalo ESC lines derived from IVF, parthenogenesis, and HMC embryos may be genetically manipulated to provide a powerful tool for studies involving embryonic development, genomic imprinting, gene targeting, cloning, chimera formation, and transgenic animal production.

  1. Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas

    PubMed Central

    Riegler, Johannes; Ebert, Antje; Qin, Xulei; Shen, Qi; Wang, Mouer; Ameen, Mohamed; Kodo, Kazuki; Ong, Sang-Ging; Lee, Won Hee; Lee, Grace; Neofytou, Evgenios; Gold, Joseph D.; Connolly, Andrew J.; Wu, Joseph C.

    2016-01-01

    Summary The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm3. A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm3 and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking. PMID:26777057

  2. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    2016-01-01

    Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

  3. Gravitropism in Leafy Dicot Stems

    NASA Technical Reports Server (NTRS)

    Salisbury, F. B.

    1985-01-01

    A polarizing research microscope with rotating stage and associated camera equipment were ordered, and techniques of fixation and preparation of specimens were perfected for studying possible changes in orientation of cellulose microfibrils in cell walls of gravistimulated dicot stems. Acid ethephon solutions or acid without ethephon caused elongation of stem tissues where they were applied; stems bent away from the side of application. Acid solutions applied to the bottom of horizontal stems greatly delayed bending. Research in tissue sensitivity changes during gravitropic bending of soybean hypocotyls while immersed in auxin and in castor bean stems is also reported.

  4. Stem cells and transplant arteriosclerosis.

    PubMed

    Xu, Qingbo

    2008-05-01

    Stem cells can differentiate into a variety of cells to replace dead cells or to repair damaged tissues. Recent evidence indicates that stem cells are involved in the pathogenesis of transplant arteriosclerosis, an alloimmune initiated vascular stenosis that often results in transplant organ failure. Although the pathogenesis of transplant arteriosclerosis is not yet fully understood, recent developments in stem cell research have suggested novel mechanisms of vascular remodeling in allografts. For example, stem cells derived from the recipient may repair damaged endothelial cells of arteries in transplant organs. Further evidence suggests that stem cells or endothelial progenitor cells may be released from both bone marrow and non-bone marrow tissues. Vascular stem cells appear to replenish cells that died in donor vessels. Concomitantly, stem/progenitor cells may also accumulate in the intima, where they differentiate into smooth muscle cells. However, several issues concerning the contribution of stem cells to the pathogenesis of transplant arteriosclerosis are controversial, eg, whether bone marrow-derived stem cells can differentiate into smooth muscle cells that form neointimal lesions of the vessel wall. This review summarizes recent research on the role of stem cells in transplant arteriosclerosis, discusses the mechanisms of stem cell homing and differentiation into mature endothelial and smooth muscle cells, and highlights the controversial issues in the field.

  5. Materials as stem cell regulators

    NASA Astrophysics Data System (ADS)

    Murphy, William L.; McDevitt, Todd C.; Engler, Adam J.

    2014-06-01

    The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine.

  6. Statins and stem cell modulation.

    PubMed

    Xu, Hui; Yang, Yue-Jin; Yang, Tao; Qian, Hai-Yan

    2013-01-01

    Stem cell-based therapy is a promising option for the treatment of ischemic heart diseases. As to a successful stem cell-based therapy, one of the most important issues is that the stable engraftment and survival of implanted stem cells in cardiac microenvironment. There are evidences suggest that pharmacological treatment devoted to regulate stem cell function might represent a potential new therapeutic strategy and are drawing nearer to becoming a part of treatment in clinical settings. Statins could exert cholesterol-independent or pleiotropic effects to cardiovascular system. Recent studies have shown that statins could modulate the biological characteristics and function of various stem cells, thus could be an effective method to facilitate stem cell therapy. This review will focus on statins and their modulation effects on various stem cells.

  7. [Perinatal sources of stem cells].

    PubMed

    Piskorska-Jasiulewicz, Magdalena Maria; Witkowska-Zimny, Małgorzata

    2015-03-08

    Recently, stem cell biology has become an interesting topic. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Successful application of hematopoietic stem cells in hematology has led to the search for other sources of stem cells and expanding the scale of their application. Perinatal stem cells are a versatile cell population, and they are interesting for both scientific and practical objectives. Stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in the case of genetic disorders. In this review paper we focus on the extraction and therapeutic potential of stem cells derived from perinatal tissues such as the placenta, the amnion, amniotic fluid, umbilical cord blood and Wharton's jelly.

  8. Materials as stem cell regulators

    PubMed Central

    Murphy, William L.; McDevitt, Todd C.; Engler, Adam J.

    2014-01-01

    The stem cell/material interface is a complex, dynamic microenvironment in which the cell and the material cooperatively dictate one another's fate: the cell by remodelling its surroundings, and the material through its inherent properties (such as adhesivity, stiffness, nanostructure or degradability). Stem cells in contact with materials are able to sense their properties, integrate cues via signal propagation and ultimately translate parallel signalling information into cell fate decisions. However, discovering the mechanisms by which stem cells respond to inherent material characteristics is challenging because of the highly complex, multicomponent signalling milieu present in the stem cell environment. In this Review, we discuss recent evidence that shows that inherent material properties may be engineered to dictate stem cell fate decisions, and overview a subset of the operative signal transduction mechanisms that have begun to emerge. Further developments in stem cell engineering and mechanotransduction are poised to have substantial implications for stem cell biology and regenerative medicine. PMID:24845994

  9. Evaluation of serum PIVKA-II and MIF as diagnostic markers for HCV/HBV induced hepatocellular carcinoma.

    PubMed

    Kamel, Mahmoud M; Saad, Mohamed F; Mahmoud, Amal A; Edries, Awatief A; Abdel-Moneim, Ahmed S

    2014-12-01

    Viral hepatitis is the most significant predisposing factor for hepatocellular carcinoma (HCC). Liver cancer grows silently with mild or no symptoms until the disease is advanced and with little hope of cure. Early recognition of the onset of HCC would help to select more effective therapies for patients leading to a better prognosis and life span. The current study aims to evaluate two diagnostic and prognostic markers - Prothrombin induced by vitamin K absence-II (PIVKA-II) and macrophage migration inhibitory factor (MIF) in the serum of patients with HCC and those with a high risk of developing hepatic cancers. Serum samples from hepatocellular carcinoma, hepatitis C and normal subjects were subjected to quantitative determinations of different parameters including alpha-fetoprotein (AFP), PIVKA-II and MIF. Significant differences between the various groups were recorded. PIVKA-II and AFP showed a higher specificity and sensitivity compared to MIF, and there was considerable correlation between AFP and both PIVKA and MIF. It is concluded that analysis of PIVKA-II and AFP can serve as useful non-invasive markers for the early detection of HCC with good sensitivity and specificity.

  10. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation

    PubMed Central

    Cillo, Umberto; Giuliani, Tommaso; Polacco, Marina; Herrero Manley, Luz Maria; Crivellari, Gino; Vitale, Alessandro

    2016-01-01

    Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients. PMID:26755873

  11. Integrated microfluidic device for serum biomarker quantitation using either standard addition or a calibration curve.

    PubMed

    Yang, Weichun; Sun, Xiuhua; Wang, Hsiang-Yu; Woolley, Adam T

    2009-10-01

    Detection and accurate quantitation of biomarkers such as alpha-fetoprotein (AFP) can be a key aspect of early stage cancer diagnosis. Microfluidic devices provide attractive analysis capabilities, including low sample and reagent consumption, as well as short assay times. However, to date microfluidic analyzers have relied almost exclusively on calibration curves for sample quantitation, which can be problematic for complex mixtures such as human serum. We have fabricated integrated polymer microfluidic systems that can quantitatively determine fluorescently labeled AFP in human serum using either the method of standard addition or a calibration curve. Our microdevices couple an immunoaffinity purification step with rapid microchip electrophoresis separation in a laser-induced fluorescence detection system, all under automated voltage control in a miniaturized polymer microchip. In conjunction with laser-induced fluorescence detection, these systems can quantify AFP at approximately 1 ng/mL levels in approximately 10 microL of human serum in a few tens of minutes. Our polymer microdevices have been applied in determining AFP in spiked serum samples. These integrated microsystems offer excellent potential for rapid, simple, and accurate biomarker quantitation in a point-of-care setting.

  12. Liver Full Reference Set Application: Hiro Yamada - Wako (2011) — EDRN Public Portal

    Cancer.gov

    Wako has received new 510(k) clearance for Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and Des-gamma-carboxy prothrombin (DCP) tests on an innovative μTASWako i30 analyzer from FDA. The AFP-L3 and DCP assayed on an older platform LiBASys have been cleared with indication of use for risk assessment of hepatocellular carcinoma (HCC) in patient at risk for the liver malignancy. Wako believes that early detection of HCC is critical for improving HCC patient outcome. Therefore, Wako is currently seeking collaborative opportunities to retrospectively measure clinical samples using the AFP-L3 and DCP for further determining of effectiveness of the HCC biomarkers in early detection which are collected prospectively during HCC surveillance. The Reference Sample Set in the EDRN biorepository are well characterized and studied. Access to these samples would allow Wako to quickly determine the clinical effectiveness of AFP-L3 and DCP in detecting early HCC

  13. Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

    PubMed

    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Ludovico Rapaccini, Gian; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-04-01

    Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

  14. Evaluation of serum PIVKA-II and MIF as diagnostic markers for HCV/HBV induced hepatocellular carcinoma.

    PubMed

    Kamel, Mahmoud M; Saad, Mohamed F; Mahmoud, Amal A; Edries, Awatief A; Abdel-Moneim, Ahmed S

    2014-12-01

    Viral hepatitis is the most significant predisposing factor for hepatocellular carcinoma (HCC). Liver cancer grows silently with mild or no symptoms until the disease is advanced and with little hope of cure. Early recognition of the onset of HCC would help to select more effective therapies for patients leading to a better prognosis and life span. The current study aims to evaluate two diagnostic and prognostic markers - Prothrombin induced by vitamin K absence-II (PIVKA-II) and macrophage migration inhibitory factor (MIF) in the serum of patients with HCC and those with a high risk of developing hepatic cancers. Serum samples from hepatocellular carcinoma, hepatitis C and normal subjects were subjected to quantitative determinations of different parameters including alpha-fetoprotein (AFP), PIVKA-II and MIF. Significant differences between the various groups were recorded. PIVKA-II and AFP showed a higher specificity and sensitivity compared to MIF, and there was considerable correlation between AFP and both PIVKA and MIF. It is concluded that analysis of PIVKA-II and AFP can serve as useful non-invasive markers for the early detection of HCC with good sensitivity and specificity. PMID:25448465

  15. A comparative study of four serological tumor markers for the detection of breast cancer.

    PubMed

    Clinton, Shawn R; Beason, Kevin L; Bryant, Sabrina; Johnson, James T; Jackson, Margaret; Wilson, Cynthia; Holifield, Kay; Vincent, Charlton; Hall, Margot

    2003-01-01

    Breast cancer is currently the third most common cause of cancer in the world. Circulating tumor antigens are often used as a minimally invasive tool for noting breast cancer progression. The objective of this study was to compare four tumor antigens (CA 15-3, CA 27.29, alpha-fetoprotein [AFP], and carcinoembryonic antigen [CEA]) for their diagnostic efficacy in breast cancer patients. It was hypothesized that CA 15-3 would proved to be superior to CA 27.29, CEA, and AFP in assay performance. Tumor marker assays were performed according to the manufacturers' directions. Assays used in this study were CA 15-3 and CA 27.29 (Fujirebio Diagnostics/Centocor Inc.), AFP (Abbott Inc.), and CEA (Hybritech Inc.). A total of 554 patient samples were obtained from an area hospital, plus 200 healthy adult samples which were used for the determination of normal reference intervals. The patients included patients with no disease (184), with non-malignant disease (11), with breast cancer (87), and with other types of cancer (272). Diagnostic percent sensitivities for each marker were: CA 15-3 (63%), CA 27.29 (39%), CEA (22%), and AFP (22%). Diagnostic specificities for each marker were comparable, ranging from 80-88%. Analytical parameters were evaluated for the assays and compared favorably. We concluded that CA 15-3 was the best tumor antigen for use as a diagnostic aid and monitoring agent.

  16. Impact Factors for Microinvasion in Patients With Hepatocellular Carcinoma: Possible Application to the Definition of Clinical Tumor Volume

    SciTech Connect

    Wang Minhua; Ji Yuan; Zeng Zhaochong; Tang Zhaoyou; Fan Jia; Zhou Jian; Zeng Mengsu; Bi Aihong; Tan Yunshan

    2010-02-01

    Purpose: To evaluate the degree of invasion of hepatocellular carcinoma (HCC) microscopically that will provide a potential application for gross tumor volume to clinical tumor volume (GTV-to-CTV) expansion. Methods and Materials: From January 2002 to January 2006, 149 HCC patients were selected from those who had undergone surgical resection. Pathology slides and clinical data of all patients were reviewed, including platelet counts, serum alpha-fetoprotein (AFP) levels, degree of liver cirrhosis, tumor size, capsular status, portal vein invasion, TNM stage, and histologic tumor grade. The distance between the tumor margin (or fibrous capsule) and the invasive lesions was measured by senior pathologists. Results: Of these 149 patients, 79 (53.0%) patients presented with tumor microinvasion between 0.5 and 4 mm. This degree of microinvasion was inversely correlated with lower platelet counts and positively correlated with higher AFP levels, larger tumor sizes, portal vein invasion, and advanced TNM stage. Microinvasion distances less than or equal to 2 mm were found in 96.1% of patients (74/77) with tumor dimensions less than or equal to 5 cm and in 94.5% of patients (85/90) with AFP levels less than 400 mug/l. Conclusions: Based on our study findings, GTV-to-CTV expansions of 4 mm for HCC are required to conceal the gross tumor and any microscopic disease with 100% accuracy. Tumor size and AFP levels are the simplest indicators for determining the GTV-to-CTV distance for HCC.

  17. Association of abnormal plasma bilirubin with aggressive hepatocellular carcinoma phenotype.

    PubMed

    Carr, Brian I; Guerra, Vito; Giannini, Edoardo G; Farinati, Fabio; Ciccarese, Francesca; Ludovico Rapaccini, Gian; Di Marco, Maria; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-04-01

    Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness.

  18. Self-renewal of human embryonic stem cells on defined synthetic electrospun nanofibers.

    PubMed

    Kumar, Deepak; Dale, Tina P; Yang, Ying; Forsyth, Nicholas R

    2015-12-01

    Human embryonic stem cells (hESCs) are conventionally expanded and maintained in vitro on biological substrates. Synthetic electrospun polymer nanofibers have the potential to act as non-biological substrates in the culture of hESCs. Three synthetic, FDA approved polymers: poly-ɛ-caprolactone (PCL), poly-L-lactic acid (PLLA) and poly lactic-co-glycolic acid (PLGA) were electrospun as nanofibers (random or aligned conformations) on glass coverslips and their supportive role in hESC culture examined. Clonogenicity experiments demonstrated that nanofibrous scaffolds (PCL aligned and random, PLLA aligned and PLGA aligned) supported hESC adhesion and expansion. A significantly greater number of colonies were observed on PCL-aligned nanofibrous scaffolds in comparison to PLLA-aligned and PLGA-aligned substrates (p < 0.05). hESC colonies were significantly larger on PCL aligned nanofibrous substrates when compared to other polymer substrates (p < 0.05-0.001), where fiber diameter played a pivotal role in support of hESC clonogenicity (on PCL). Retention of pluripotentiality was confirmed by expression of Alkaline phosphatase, OCT-3/4 and Nanog expression on PCL scaffolds and the expression of transcripts representative of mesoderm (ACTC1), ectoderm (SOX1) and endoderm (AFP) during subsequent spontaneous in vitro differentiation. These results demonstrate the potential of nanofibers as xeno-free scaffolds supportive of hESC adhesion, self-renewal and differentiation in in vitro culture conditions. PMID:26610861

  19. Shortening and Improving the Embryonic Stem Cell Test through the Use of Gene Biomarkers of Differentiation

    PubMed Central

    Romero, Andrea C.; Vilanova, Eugenio; Sogorb, Miguel A.

    2011-01-01

    The embryonic Stem cell Test (EST) is a validated assay for testing embryotoxicity in vitro. The total duration of this protocol is 10 days, and its main end-point is based on histological determinations. It is suggested that improvements on EST must be focused toward molecular end-points and, if possible, to reduce the total assay duration. Five days of exposure of D3 cells in monolayers under spontaneous differentiation to 50 ng/mL of the strong embryotoxic 5-fluorouracil or to 75 μg/mL of the weak embryotoxic 5,5-diphenylhydeantoin caused between 20 and 74% of reductions in the expression of the following genes: Pnpla6, Afp, Hdac7, Vegfa, and Nes. The exposure to 1 mg/mL of nonembryotoxic saccharin only caused statistically significant reductions in the expression of Nes. These exposures reduced cell viability of D3 cells by 15, 28, and 34%. We applied these records to the mathematical discriminating function of the EST method to find that this approach is able to correctly predict the embryotoxicity of all three above-mentioned chemicals. Therefore, this work proposes the possibility of improve EST by reducing its total duration and by introducing gene expression as biomarker of differentiation, which might be very interesting for in vitro risk assessment embryotoxicity. PMID:21876691

  20. Assessment of the role of interleukin-6 in diagnosis of hepatocellular carcinoma.

    PubMed

    El-Folly, Runia Fouad; El-Kabarity, Rania Hamdy; Arafa, Naglaa A

    2010-01-01

    Interleukin-6 (IL-6) is a promising tumor marker for hepatocellular carcinoma; HCC. IL-6 may help to identify a subset of HCC patients with low alpha-fetoprotein (AFP) level, and may serve as complementary tumor marker, however, this has to be clarified. This study assesses the value of measuring serum level of interleukin-6 in patients with chronic liver disease and HCC, and evaluates its sensitivity and specificity in comparison to AFP in early diagnosis of HCC. Seventy five patients with chronic liver disease (CLD) with or without HCC and 25 healthy controls were included. Patients were divided into Group I: 25 patients with CLD but no evidence of HCC. Group II: 25 patients with HCC on top of post-viral hepatitic with elevation in AFP (> 200 ng); and Group III: 25 patients with HCC on top of post-viral hepatitic but without elevation in AFP (< 200 ng). Analysis of the mean serum IL-6 levels revealed a statistically significant difference between all groups (P < 0.01). A significant positive correlation was found between mean levels of IL- 6 & AFP in HCC (P < 0.05), the mean IL-6 levels in patients with Child classification C was higher than in those with Child A and B.After adjustment using multiple logistic regressions, only loss of weight and AFP were found to be significantly associated with HCC (P < 0.05). It is concluded that the diagnostic value of IL-6 increased when it is associated with AFP measurement. Combining the two markers can provide a new perspective in the diagnosis of HCC.

  1. Dental mesenchymal stem cells.

    PubMed

    Sharpe, Paul T

    2016-07-01

    Mammalian teeth harbour mesenchymal stem cells (MSCs), which contribute to tooth growth and repair. These dental MSCs possess many in vitro features of bone marrow-derived MSCs, including clonogenicity, expression of certain markers, and following stimulation, differentiation into cells that have the characteristics of osteoblasts, chondrocytes and adipocytes. Teeth and their support tissues provide not only an easily accessible source of MSCs but also a tractable model system to study their function and properties in vivo In addition, the accessibility of teeth together with their clinical relevance provides a valuable opportunity to test stem cell-based treatments for dental disorders. This Review outlines some recent discoveries in dental MSC function and behaviour and discusses how these and other advances are paving the way for the development of new biologically based dental therapies. PMID:27381225

  2. Global STEM Navigators

    ERIC Educational Resources Information Center

    Dalimonte, Cathy

    2013-01-01

    In the STEM classroom, students can work in collaborative teams to build those essential skills needed for the 21st-century world. In project-based learning (PBL), teams of four to six students are often randomly selected to describe a realistic situation that may occur in today's workplace; this may be done by counting off in fours, fives,…

  3. Common stemness regulators of embryonic and cancer stem cells.

    PubMed

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-10-26

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.

  4. Common stemness regulators of embryonic and cancer stem cells

    PubMed Central

    Hadjimichael, Christiana; Chanoumidou, Konstantina; Papadopoulou, Natalia; Arampatzi, Panagiota; Papamatheakis, Joseph; Kretsovali, Androniki

    2015-01-01

    Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies. PMID:26516408

  5. Melanocytes, melanocyte stem cells, and melanoma stem cells.

    PubMed

    Lang, Deborah; Mascarenhas, Joseph B; Shea, Christopher R

    2013-01-01

    Melanocyte stem cells differ greatly from melanoma stem cells; the former provide pigmented cells during normal tissue homeostasis and repair, and the latter play an active role in a lethal form of cancer. These 2 cell types share several features and can be studied by similar methods. Aspects held in common by both melanocyte stem cells and melanoma stem cells include their expression of shared biochemical markers, a system of similar molecular signals necessary for their maintenance, and a requirement for an ideal niche microenvironment for providing these factors. This review provides a perspective of both these cell types and discusses potential models of stem cell growth and propagation. Recent findings provide a strong foundation for the development of new therapeutics directed at isolating and manipulating melanocyte stem cells for tissue engineering or at targeting and eradicating melanoma specifically, while sparing nontumor cells.

  6. Stem cell aging

    PubMed Central

    Muller-Sieburg, Christa; Sieburg, Hans B.

    2009-01-01

    The question whether stem cells age remains an enigma. Traditionally, aging was thought to change the properties of hematopoietic stem cells (HSC). We discuss here a new model of stem cell aging that challenges this view. It is now well-established that the HSC compartment is heterogeneous, consisting of epigenetically fixed subpopulations of HSC that differ in self-renewal and differentiation capacity. New data show that the representation of these HSC subsets changes during aging. HSC that generate lymphocyte-rich progeny are depleted, while myeloid-biased HSC are enriched in the aged HSC compartment. Myeloid-biased HSC, even when isolated from young donors, have most of the characteristics that had been attributed to aged HSC. Thus, the distinct behavior of the HSC isolated from aged hosts is due to the accumulation of myeloid-biased HSC. By extension this means that the properties of individual HSC are not substantially changed during the lifespan of the organism and that aged hosts do not contain many aged HSC. Myeloid-biased HSC give rise to mature cells slowly but contribute for a long time to peripheral hematopoiesis. We propose that such slow, “lazy” HSC are less likely to be transformed and therefore may safely sustain hematopoiesis for a long time. PMID:19066464

  7. Undifferentiated embryonal sarcoma of the liver with an unusual presentation: case report and review of the literature

    PubMed Central

    Lei, Li; Zuppan, Craig W.; Raza, Anwar S.

    2016-01-01

    Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant mesenchymal neoplasm, relatively unique to the liver that occurs primarily in children and teenagers. Delay in diagnosis is not uncommon due to lack of a characteristic clinical presentation, serological markers and radiological changes. We report a case of UESL in a 9-year-old girl who presented with right upper quadrant pain and a palpable mass. Laboratory and imaging workup revealed a complex hepatic cyst, increased IgE, transient peripheral eosinophilia and a normal alpha-fetoprotein (AFP). Initial empirical treatment with albendazole was implemented for presumed hydatid cyst disease, but the child failed to improve. Subsequent surgical resection resulted in the correct diagnosis of UESL. She received 6 months of chemotherapy and remains well with no evidence of tumor about 12 months after resection. We herein review the typical clinical, radiologic and pathologic features of this rare tumor. PMID:27034807

  8. Labeling of human hepatocellular carcinoma cells by hexamethylene diamine modified fluorescent carbon dots

    NASA Astrophysics Data System (ADS)

    Dong, Wei; Dong, Yan; Wang, Ying; Zhou, Shiqi; Ge, Xin; Sui, Lili; Wang, Jingwen

    2013-12-01

    Fluorescent carbon dots (CDs) were synthesized by a solvothermal method with glucose as carbon source and surface-modified with 1,6-hexamethylene diamine. In this hybrid CDs, the modification played important role for improving the fluorescent performance by introducing nitrogenous compound to passivate CD's surface, making the CDs emit strong fluorescence. The as-prepared CDs were linked with mouse anti-human Alpha fetoprotein (AFP) antibody and goat anti-mouse immunoglobulin (IgG) to directly and indirectly label fixed human hepatocellular carcinoma cells, respectively. The cytotoxicity of these CDs were also tested using the human hepatocellular carcinoma cells. No apparent cytotoxicity was observed, which suggested the potential application of the as-prepared CDs in bioimaging.

  9. Biomarkers for hepatocellular carcinoma: progression in early diagnosis, prognosis, and personalized therapy

    PubMed Central

    2013-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Currently, surgical resection, liver transplantation, and local ablation are considered curative therapeutic practices for HCC. The diagnosis of HCC without pathologic confirmation is achieved by analyzing serum alpha-fetoprotein (AFP) levels combined with imaging techniques, including ultrasonography, magnetic resonance imaging, and computerized tomography. Although progress has been made in the diagnosis and management of HCC, its prognosis remains dismal. Various new technologies have identified numerous novel biomarkers with potential diagnostic as well as prognostic value, including Dickkopf-1 and Golgi protein 73. These biomarkers not only help in the early diagnosis and prediction of prognosis, but also assist in identifying potential targets for therapeutic interventions. In this article, we provide an up-to-date review of the biomarkers that are used for early diagnosis, prognosis prediction, and personalized treatment of HCC. PMID:24252133

  10. Stem cells and neurodegenerative diseases.

    PubMed

    Hou, LingLing; Hong, Tao

    2008-04-01

    Neurodegenerative diseases are characterized by the neurodegenerative changes or apoptosis of neurons involved in networks, which are important to specific physiological functions. With the development of old-aging society, the incidence of neurodegenerative diseases is on the increase. However, it is difficult to diagnose for most of neurodegenerative diseases. At present, there are too few effective therapies. Advances in stem cell biology have raised the hope and possibility for the therapy of neurodegenerative diseases. Recently, stem cells have been widely attempted to treat neurodegenerative diseases of animal model. Here we review the progress and prospects of various stem cells, including embryonic stem cells, mesenchymal stem cell and neural stem cells and so on, for the treatments of neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Huntington' disease and Amyotrophic lateral sclerosis/Lou Gehrig's disease.

  11. Clinical Significance of Plasma Osteopontin Level as a Biomarker of Hepatocellular Carcinoma

    PubMed Central

    Salem, Mona; Atti, Sahar Abdel; Raziky, Maisa El; Darweesh, Samar Kamal; Sharkawy, Marwa El

    2013-01-01

    Background Biomarkers of hepatocellular carcinoma (HCC) are helpful in screening, diagnosis and follow up of cases. Osteopontin (OPN) is a glycoprotein secreted by osteoblasts, osteoclasts, macrophages and T cells, and is over-expressed in a variety of tumors, including carcinomas of liver, stomach, breast, lung, colon, and prostate. So, the aim of this study was to verify the possibility of using the plasma Osteopontin level as a biomarker for diagnosis of HCC. Methods The study included 70 subjects divided into three groups: group I had 30 patients with HCC (proved by histopathology or combined spiral CT and elevated alpha-fetoprotein) on top of HCV, group II had 30 patients with HCV infection and group III had 10 healthy subjects serving as control. Osteopontin level was measured in plasma of the studied subjects by ELISA, serum alpha fetoprotein (AFP) level was also measured by EIA. Results Osteopontin levels were significantly elevated in patients with HCC and in HCV patients in comparison to control group (P: 0.005). There was significant correlation between OPN and AFP levels (P: 0.00). The sensitivity and specificity of OPN for selective detection of HCC group over the non-HCC group (HCV group and healthy control group) were73% and 54%, respectively, at a cut-off value of 128.5 ng/mL. Plasma OPN levels directly correlated with the tumor number but not with the size of the tumor (P: 0.00). Conclusion Plasma OPN level appears to be an additional biomarker for HCC detection.

  12. Contrasting views on STEM employment

    NASA Astrophysics Data System (ADS)

    Jones, Matthew; Huber, Michael

    2015-07-01

    In reply to “Unemployed and STEM” (Careers, May pp46-47), in which Penny Jackson described how her efforts to find a job in science, technology, engineering or mathematics (STEM) met with little success at first, even though she has a BSc in physics and a Master's in accelerator science. And in reply to “STEM paradox revisited” (Editorial, June p15), on why employers are expressing concerns about STEM shortages at a time when many recent STEM graduates are struggling to find jobs.

  13. Characterization of amniotic stem cells.

    PubMed

    Koike, Chika; Zhou, Kaixuan; Takeda, Yuji; Fathy, Moustafa; Okabe, Motonori; Yoshida, Toshiko; Nakamura, Yukio; Kato, Yukio; Nikaido, Toshio

    2014-08-01

    The amnion membrane is developed from embryo-derived cells, and amniotic cells have been shown to exhibit multidifferentiation potential. These cells represent a desirable source for stem cells for a variety of reasons. However, to date very few molecular analyses of amnion-derived cells have been reported, and efficient markers for isolating the stem cells remain unclear. This paper assesses the characterization of amnion-derived cells as stem cells by examining stemness marker expressions for amnion-derived epithelial cells and mesenchymal cells by flow cytometry, immunocytochemistry, and quantitative PCR. Flow cytometry revealed that amnion epithelial cells expressed CD133, CD 271, and TRA-1-60, whereas mecenchymal cells expressed CD44, CD73, CD90, and CD105. Immunohistochemistry showed that both cells expressed the stemness markers Oct3/4, Sox2, Klf4, and SSEA4. Stemness genes' expression in amnion epithelial cells, mesenchymal cells, fibroblast, bone marrow-derived mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs) was compared by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Amnion-derived epithelial cells and mesenchymal cells expressed Oct3/4, Nanog, and Klf4 more than bone marrow-derived MSCs. The sorted TRA1-60-positive cells expressed Oct3/4, Nanog, and Klf4 more than unsorted cells or TRA1-60-negative cells. TRA1-60 can be a marker for isolating amnion epithelial stem cells.

  14. Mechanotransduction: Tuning Stem Cells Fate

    PubMed Central

    D'Angelo, Francesco; Tiribuzi, Roberto; Armentano, Ilaria; Kenny, Josè Maria; Martino, Sabata; Orlacchio, Aldo

    2011-01-01

    It is a general concern that the success of regenerative medicine-based applications is based on the ability to recapitulate the molecular events that allow stem cells to repair the damaged tissue/organ. To this end biomaterials are designed to display properties that, in a precise and physiological-like fashion, could drive stem cell fate both in vitro and in vivo. The rationale is that stem cells are highly sensitive to forces and that they may convert mechanical stimuli into a chemical response. In this review, we describe novelties on stem cells and biomaterials interactions with more focus on the implication of the mechanical stimulation named mechanotransduction. PMID:24956164

  15. STEm Minority Graduate Program

    SciTech Connect

    Nicholas, Kaen E

    2012-09-20

    ABSTRACT The state of science, technology, engineering and math (STEM) education in the United States has seen some unfavorable assessments over the past decade. In early February, 2010 the House of Representatives heard testimony on undergraduate and graduate education. The message from the panel, which included experts from academia, STEM-based industries, and the National Science Foundation (NSF) was dire and required an urgent response. The experts along with the committee's chairperson, U. S. Representative Daniel Lipinski (D-IL) cited that the complexity of Science, Technology, Engineering, and Mathematics applications and coursework and the methodology utilized to teach these subjects are forcing students out of these disciplines. As the National Academies described in its 2007 report Rising Above the Gathering Storm, successful STEM education is not just an academic pursuit it's a necessity for competing in the knowledge-based economy that the United States had a key role in creating. The potential for action is being made available again as the America COMPETES Act of 2007 is up for reauthorization. Its initial focus was on STEM education at the K-12 levels, but efforts at the undergraduate and graduate levels are needed to retain students to fill the jobs left vacant as baby boomers retire. The Educational Advancement Alliance, Inc. (EAA) has for two decades created programs that have not only addressed the issues of ensuring that students are aptly prepared for college but have focused its efforts over the past decade on increasing the number of students who pursue degrees in STEM disciplines. For the EAA, the introduction of the wonders of science begins at the elementary and middle school level via the Learning Lab, a state-of-the-art mobile science laboratory that visits students in grades 4-6 at the various schools throughout Philadelphia and The Math/Tech Academy which meets on Saturdays for students in grades 5-7. For the past two years the EAA has

  16. Advancing the STEM Workforce through STEM-Centric Career Development

    ERIC Educational Resources Information Center

    Feller, Rich

    2011-01-01

    Preparing for the future is not what it used to be. Yet, advising students, preparing lessons, and promoting the value of STEM options remains constant. As a result, technical and engineering educators seek clarity about the future of careers, career development, and ways to promote STEM options. Recently, the ITEEA conference allowed the author…

  17. Stem Cells, Redox Signaling, and Stem Cell Aging

    PubMed Central

    Liang, Raymond

    2014-01-01

    Abstract Significance: Functional stem cell decline has been postulated to result in loss of maintenance of tissue homeostasis leading to organismal decline and diseases of aging. Recent Advances: Recent findings implicate redox metabolism in the control of stem cell pool and stem cell aging. Although reactive oxygen species (ROS) are better known for their damaging properties to DNA, proteins and lipids, recent findings suggest that ROS may also be an integral physiological mediator of cellular signaling in primary cells. Critical Issues: Here we review recent published work on major signaling pathways and transcription factors that are regulated by ROS and mediate ROS regulation of stem cell fate. We will specifically focus on how alterations in this regulation may be implicated in disease and particularly in diseases of stem cell aging. In general, based on the work described here we propose a model in which ROS function as stem cell rheostat. Future Directions: Future work in elucidating how ROS control stem cell cycling, apoptotic machinery, and lineage determination should shed light on mechanisms whereby ROS may control stem cell aging. Antioxid. Redox Signal. 20, 1902–1916. PMID:24383555

  18. An Ecological Model of STEM Education: Operationalizing STEM FOR ALL

    ERIC Educational Resources Information Center

    Basham, James D.; Israel, Maya; Maynard, Kathie

    2010-01-01

    This article describes a framework for how to provide more accessible, relevant, and effective instruction in science, technology, engineering, and mathematics (STEM) education to all students. The STEM for All initiative asserts that all students, including those with disabilities and other diverse learning needs, should be included in meaningful…

  19. Are STEM High School Students Entering the STEM Pipeline?

    ERIC Educational Resources Information Center

    Franco, M. Suzanne; Patel, Nimisha H.; Lindsey, Jill

    2012-01-01

    This study compared the career skills and interests for students in two STEM schools to national data. Students completed the KUDER skills assessment and career planning online tools. Results were compared across school, grade level, and sex. The results provided evidence that STEM high school students expressed career intents in predominately…

  20. 5. VIEW SHOWING UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW SHOWING UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE, WITH LOG ACCESS STRUCTURE, LOOKING SOUTHEAST - High Mountain Dams in Upalco Unit, Bluebell Lake Dam, Ashley National Forest, 11.2 miles Northwest of Swift Creek Campground, Mountain Home, Duchesne County, UT

  1. 6. VIEW SHOWING UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. VIEW SHOWING UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE, WITH LOG ACCESS STRUCTURE, LOOKING WEST - High Mountain Dams in Upalco Unit, Bluebell Lake Dam, Ashley National Forest, 11.2 miles Northwest of Swift Creek Campground, Mountain Home, Duchesne County, UT

  2. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2009-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  3. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2002-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  4. Skeletal stem cells

    PubMed Central

    Bianco, Paolo; Robey, Pamela G.

    2015-01-01

    Skeletal stem cells (SSCs) reside in the postnatal bone marrow and give rise to cartilage, bone, hematopoiesis-supportive stroma and marrow adipocytes in defined in vivo assays. These lineages emerge in a specific sequence during embryonic development and post natal growth, and together comprise a continuous anatomical system, the bone-bone marrow organ. SSCs conjoin skeletal and hematopoietic physiology, and are a tool for understanding and ameliorating skeletal and hematopoietic disorders. Here and in the accompanying poster, we concisely discuss the biology of SSCs in the context of the development and postnatal physiology of skeletal lineages, to which their use in medicine must remain anchored. PMID:25758217

  5. The advantages of hair follicle pluripotent stem cells over embryonic stem cells and induced pluripotent stem cells for regenerative medicine.

    PubMed

    Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2010-12-01

    Multipotent adult stem cells have many potential therapeutic applications. Our recent findings suggest that hair follicles are a promising source of easily accessible multipotent stem cells. Stem cells in the hair follicle area express the neural stem cell marker nestin, suggesting that hair-follicle stem cells and neural stem cells have common features. Nestin-expressing hair follicle stem cells can form neurons and other cell types, and thus adult hair follicle stem cells could have important therapeutic applications, particularly for neurologic diseases. Transplanted hair follicle stem cells promote the functional recovery of injured peripheral nerve and spinal cord. Recent findings suggest that direct transplantation of hair-follicle stem cells without culture can promote nerve repair, which makes them potentially clinically practical. Human hair follicle stem cells as well as mouse hair follicle stem cells promote nerve repair and can be applied to test the hypothesis that human hair follicle stem cells can provide a readily available source of neurologically therapeutic stem cells. The use of hair follicle stem cells for nerve regeneration overcomes critical problems of embryonic stem cells or induced pluripotent stem cells in that the hair follicle stem cells are multipotent, readily accessible, non-oncogenic, and are not associated with ethical issues.

  6. FDA Warns About Stem Cell Claims

    MedlinePlus

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Claims Share Tweet Linkedin Pin it More sharing ... blood-forming system. back to top Regulation of Stem Cells FDA regulates stem cells in the U.S. to ...

  7. Gastrointestinal stem cell up-to-date.

    PubMed

    Pirvulet, V

    2015-01-01

    Cellular and tissue regeneration in the gastrointestinal tract depends on stem cells with properties of self-renewal, clonogenicity, and multipotency. Progress in stem cell research and the identification of potential gastric, intestinal, colonic stem cells new markers and the signaling pathways provide hope for the use of stem cells in regenerative medicine and treatments for disease. This review provides an overview of the different types of stem cells, focusing on tissue-restricted adult stem cells.

  8. Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation.

    PubMed

    Chaiteerakij, Roongruedee; Zhang, Xiaodan; Addissie, Benyam D; Mohamed, Essa A; Harmsen, William S; Theobald, Paul J; Peters, Brian E; Balsanek, Joseph G; Ward, Melissa M; Giama, Nasra H; Moser, Catherine D; Oseini, Abdul M; Umeda, Naoki; Venkatesh, Sudhakar; Harnois, Denise M; Charlton, Michael R; Yamada, Hiroyuki; Satomura, Shinji; Algeciras-Schimnich, Alicia; Snyder, Melissa R; Therneau, Terry M; Roberts, Lewis R

    2015-05-01

    Growing evidence suggests that pretransplant alpha-fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-gamma-carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow-up of 90.8 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP-L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9-6.7; P < 0.0001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4-5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3-12.0; P < 0.0001) when AFP ≥ 250 ng/mL and DCP ≥7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4-4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0-24.6; P < 0.0001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8-18.1; P < 0.0001) for outside the Milan criteria and DCP ≥7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility. PMID:25789635

  9. Breast Cancer Stem Cells

    PubMed Central

    Velasco-Velázquez, Marco A.; Homsi, Nora; De La Fuente, Marisol; Pestell, Richard G.

    2012-01-01

    Breast cancer stem cells (BCSCs) constitute a subpopulation of tumor cells that express stem cell-associated markers and have a high capacity for tumor generation in vivo. Identification of BCSCs from tumor samples or breast cancer cell lines has been based mainly on CD44+/CD24−/low or ALDH+ phenotypes. BCSCs isolation has allowed the analysis of the molecular mechanisms involved in their origin, self-renewal, differentiation into tumor cells, resistance to radiation therapy and chemotherapy, and invasiveness and metastatic ability. Molecular genetic analysis using knockout animals and inducible transgenics have identified NF-κB, c-Jun, p21CIP1, and Forkhead-like-protein Dach1 in BCSC expansion and fate. Clinical analyses of BCSCs in breast tumors have found a correlation between the proportion of BCSCs and poor prognosis. Therefore, new therapies that specifically target BCSCs are an urgent need. We summarize recent evidence that partially explain the biological characteristics of BCSCs. PMID:22249027

  10. Building STEM Opportunities for All

    ERIC Educational Resources Information Center

    Lynch, Sharon J.; Peters-Burton, Erin; Ford, Michael

    2015-01-01

    In response to a report from the President's Council of Advisors on Science and Technology, President Obama issued a challenge to the U.S. education system to create more than 1,000 new STEM-focused schools, including 200 high schools. Inclusive STEM-focused high schools--which focus their efforts on females, minorities, and students who are…

  11. Excising the Root from STEM

    ERIC Educational Resources Information Center

    Lock, Roger

    2009-01-01

    There are a number of well-intentioned STEM initiatives, some designed to improve the recruitment and retention of science teachers. Sometimes it appears that the initiators are remote from direct contact with the "grass roots" issues that feed the "stem" on which the blossoms of young enthusiastic recruits to the science teaching profession are…

  12. Trouble at the stem end

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato tubers have an axial, stem to bud polarity that is apparent at all stages of growth and development. This polarity is most evident in elongate potatoes, but is also found in “round” varieties. These differences between the stem end and other regions of the tuber establish the context for rese...

  13. STEM: Science Technology Engineering Mathematics

    ERIC Educational Resources Information Center

    Carnevale, Anthony P.; Smith, Nicole; Melton, Michelle

    2011-01-01

    The generative economic power and social influence of Science, Technology, Engineering, and Mathematics (STEM) has made the production of a capable science and engineering workforce a priority among business and policy leaders. They are rightly concerned that without a robust STEM workforce, the nation will become less competitive in the global…

  14. STEM Regional Collaboratives: The Opportunity

    ERIC Educational Resources Information Center

    Couturier, Lara K.

    2014-01-01

    Recent research has helped shift the national understanding of the opportunities presented by Science, Technology, Engineering and Math (STEM) fields, drawing attention to the large number of STEM jobs that require less than a Bachelor's degree. The data have also highlighted the critical importance of community colleges as a primary provider…

  15. AccessSTEM: Building Capacity

    ERIC Educational Resources Information Center

    DO-IT, 2009

    2009-01-01

    A series of activities were undertaken to understand the underrepresentation of people with disabilities in science, technology, engineering, and mathematics (STEM) careers and increase their participation in these fields. "AccessSTEM" collaborated with key stakeholders to conduct a "Capacity-Building Institute" ("CBI") in April 2009; share…

  16. University Festival Promotes STEM Education

    ERIC Educational Resources Information Center

    Quagliata, Andrew B.

    2015-01-01

    STEM education is argued as an essential ingredient in preparing our children for careers of the future. This study describes a university festival that includes the promotion of STEM-related career interests in young people among its goals. A total of 203 participants between the age of 7 and 17 completed both pre-event and post-event surveys. In…

  17. Engaging Students in STEM Education

    ERIC Educational Resources Information Center

    Kennedy, T. J.; Odell, M. R. L.

    2014-01-01

    With the "flattening" of the global economy in the 21st century, the teaching of Science, Technology, Engineering, and Mathematics (STEM) has taken on new importance as economic competition has become truly global. STEM education has evolved into a meta-discipline, an integrated effort that removes the traditional barriers between these…

  18. Deconstruction Geography: A STEM Approach

    ERIC Educational Resources Information Center

    Gehlhar, Adam M.; Duffield, Stacy K.

    2015-01-01

    This article will define the engineering design process used to create an integrated curriculum at STEM Center Middle School, and it features the planning, implementation, and revision of the Deconstruction Geography unit. The Science Technology Engineering and Math (STEM) Center opened in the fall of 2009 as a way to relieve overcrowding at the…

  19. The Backbone of STEM Teaching

    ERIC Educational Resources Information Center

    Gillespie, Nicole

    2015-01-01

    If we want talented young teachers to develop the capacity to get students excited about high-quality science, technology, engineering, and mathematics (STEM) learning, we must develop a network of STEM teachers who can support teachers in their continued learning about their work and enable them to collaborate with others. If we want teachers to…

  20. LncRNAs in Stem Cells

    PubMed Central

    Hu, Shanshan; Shan, Ge

    2016-01-01

    Noncoding RNAs are critical regulatory factors in essentially all forms of life. Stem cells occupy a special position in cell biology and Biomedicine, and emerging results show that multiple ncRNAs play essential roles in stem cells. We discuss some of the known ncRNAs in stem cells such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, adult stem cells, and cancer stem cells with a focus on long ncRNAs. Roles and functional mechanisms of these lncRNAs are summarized, and insights into current and future studies are presented. PMID:26880946

  1. Bioprinting for stem cell research

    PubMed Central

    Tasoglu, Savas; Demirci, Utkan

    2012-01-01

    Recently, there has been a growing interest to apply bioprinting techniques to stem cell research. Several bioprinting methods have been developed utilizing acoustics, piezoelectricity, and lasers to deposit living cells onto receiving substrates. Using these technologies, spatially defined gradients of immobilized proteins can be engineered to direct stem cell differentiation into multiple subpopulations of different lineages. Stem cells can also be patterned in a high-throughput manner onto flexible implementation patches for tissue regeneration or onto substrates with the goal of accessing encapsulated stem cell of interest for genomic analysis. Here, we review recent achievements with bioprinting technologies in stem cell research, and identify future challenges and potential applications including tissue engineering and regenerative medicine, wound healing, and genomics. PMID:23260439

  2. Stem cells: review and update.

    PubMed

    Sylvester, Karl G; Longaker, Michael T

    2004-01-01

    Regenerative medicine and emerging biotechnologies stand to revolutionize the practice of medicine. Advancements in stem cell biology, including embryonic and postnatal somatic stem cells, have made the prospect of tissue regeneration a potential clinical reality. Short of reproductive cloning, these same technologies, properly used, could allow for the creation of replacement tissue for the deficient host. To provide a concise review for surgeons on the current science and biology of stem cells, we surveyed the scientific literature, MEDLINE, and relevant political headlines that illuminate the stem cell discussion; the issues are summarized in this review. Building on this conceptual framework, the related issues of clinical promise and the political debate enveloping this emerging technology are examined. A basic understanding of stem cell biology is paramount to stay informed of this emerging technology and the national debate.

  3. Ovarian cancer stem cells enrichment.

    PubMed

    Yang, Lijuan; Lai, Dongmei

    2013-01-01

    The concept of cancer stem cells (CSCs) provides a new paradigm for understanding cancer biology. Cancer stem cells are defined as a minority of cancer cells with stem cell properties responsible for maintenance and growth of tumors. The targeting of CSCs is a potential therapeutic strategy to combat ovarian cancer. Ovarian epithelial cancer cells cultured in serum-free medium can form sphere cells. These sphere cells may be enriched for cancer stem cells (CSCs). The isolation of sphere cells from solid tumors is an important technique in studying cancer cell biology. Here we describe the isolation of sphere cells from primary ovarian cancer tissue, ascites fluid, and the cancer cell line SKOV3 with stem cell selection medium. PMID:23913228

  4. Stem cells for spine surgery.

    PubMed

    Schroeder, Joshua; Kueper, Janina; Leon, Kaplan; Liebergall, Meir

    2015-01-26

    In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer's disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion.

  5. Bi-stem gripping apparatus

    NASA Technical Reports Server (NTRS)

    Sanders, Fred G. (Inventor)

    1988-01-01

    This invention relates to devices which grip cylindrical structures and more particularly to a device which has three arcuate gripping members having frictional surfaces for gripping and compressing a bi-stem. The bi-stem gripping apparatus is constructed having a pair of side gripping members, and an intermediate gripping member disposed between them. Sheets of a gum stock silicone rubber with frictional gripping surfaces are bonded to the inner region of the gripping members and provide frictional engagement between the bi-stem and the apparatus. A latch secures the gripping apparatus to a bi-stem, and removable handles are attached, allowing an astronaut to pull the bi-stem from its cassette. A tethering ring on the outside of the gripping apparatus provides a convenient point to which a lanyard may be attached.

  6. A Comparison of Culture Characteristics between Human Amniotic Mesenchymal Stem Cells and Dental Stem Cells.

    PubMed

    Yusoff, Nurul Hidayat; Alshehadat, Saaid Ayesh; Azlina, Ahmad; Kannan, Thirumulu Ponnuraj; Hamid, Suzina Sheikh Abdul

    2015-04-01

    In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells.

  7. Stem cells, colorectal cancer and cancer stem cell markers correlations.

    PubMed

    Cherciu, Irina; Bărbălan, A; Pirici, D; Mărgăritescu, C; Săftoiu, A

    2014-01-01

    : The idea of stem cells as being progenitors of cancer was initially controversial, but later supported by research in the field of leukemia and solid tumors. Afterwards, it was established that genetic abnormalities can affect the stem and progenitor cells, leading to uncontrolled replication and deregulated differentiation. These alterations will cause the changeover to cancerous stem cells (CSC) having two main characteristics: tumor initiation and maintenance. This review will focus on the colorectal cancer stem cell (CR-CSCs) theory which provides a better understanding of different tumor processes: initiation, aggressive growth, recurrence, treatment resistance and metastasis. A search in PubMed/Medline was performed using the following keywords: colorectal cancer stem cells (CR-CSCs), colorectal neoplasms stem cells, colorectal cancer stem cell (CR-CSCs) markers, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Isolation of CR-CSCs can be achieved by targeting and selecting subpopulation of tumor cells based on expression of one or multiple cell surface markers associated with cancer self-renewal, markers as: CD133, CD166, CD44, CD24, beta1 integrin-CD29, Lgr5, EpCAM (ESA), ALDH-1, Msi-1, DCAMLK1 or EphB receptors. The identification and localization of CR-CSCs through different markers will hopefully lead to a better stratification of prognosis and treatment response, as well as the development of new effective strategies for cancer management.

  8. Leaving STEM: STEM Ph.D. Holders in Non-STEM Careers. Issue Brief

    ERIC Educational Resources Information Center

    Turk-Bicakci, Lori; Berger, Andrea

    2014-01-01

    During the last few decades, national, state, and institutional-level initiatives have been implemented to build and expand the science, technology, engineering, and mathematics (STEM) workforce by recruiting and retaining groups of individuals that have been traditionally underrepresented in STEM in higher education. The underlying theory of…

  9. The 2008 Okuda lecture: Management of hepatocellular carcinoma: from surveillance to molecular targeted therapy.

    PubMed

    Kudo, Masatoshi

    2010-03-01

    Hepatocellular carcinoma (HCC) is responsible for approximately 600,000-700,000 deaths worldwide. It is highly prevalent in the Asia-Pacific region and Africa, and is increasing in Western countries. Alpha fetoprotein (AFP) alone is insufficient for HCC screening. A combination with other tumor markers, such as PIVKA-II and AFP-L3, and periodical ultrasound surveillance is necessary. Sensitivity of AFP in depicting HCC is highest, followed by PIVKA-II and AFP-L3, but the order of the specificity is inverse, AFP-L3, PIVKA-II, and AFP. Sonazoid-enhanced ultrasound (US) is extremely useful to characterize hepatic tumors equal to or more than multidetector row computed tomography (MDCT). Sonazoid-enhanced US with defect re-perfusion imaging is a breakthrough technique in the treatment of HCC. Defect re-perfusion imaging will markedly change the therapeutic strategy for liver cancer. Gd-EOB-DTPA-magnetic resonance imaging is a newly developed imaging technique in the detection and diagnosis of HCC. It is the most sensitive tool in the differentiation of early HCC from dysplastic nodules. Regarding the treatment strategy, there has been no established systemic chemotherapy for advanced HCC, except for Sorafenib. Empirically, intrahepatic arterial infusion chemotherapy using implanted reservoir port is known to be effective in response rate and overall survival for advanced HCC with vascular invasion. Sorafenib in combination with transcatheter arterial chemoembolization or adjuvant use after ablation or resection will significantly prolong the life expectancy if ongoing clinical trials provide positive results. In conclusion, it is expected that readers will gain deeper insight into the latest progress and updated diagnosis and treatment of HCC described in this review.

  10. Biomarkers: evaluation of clinical utility in surveillance and early diagnosis for hepatocellular carcinoma.

    PubMed

    Song, Peipei; Tang, Qi; Feng, Xiaobin; Tang, Wei

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of death from cancer worldwide. Strategies to surveil and diagnose HCC in an earlier stage are urgently needed since this is when curable interventions can be offered to achieve long-term disease-free survival. Over the past few decades, research has suggested measuring alpha-fetoprotein (AFP) concentration and performing abdominal ultrasound (US) as part of routine surveillance of HCC every 6 months for high-risk patients, and many HCC guidelines worldwide have also recommended these examinations. Over the past 5 years, however, the role of serum biomarkers in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by some Western countries. In Asian countries, serum biomarkers such as AFP, the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) are still recommended for HCC surveillance and are being used as an adjunctive diagnostic tool in accordance with HCC guidelines. Moreover, novel biomarkers including Dickkopf-1 (DKK1), midkine (MDK), and microRNA (miRNA) are being studied in this regard. China accounts for 50% of HCC cases worldwide, so identifying biomarkers of HCC is paramount. Recent studies have indicated the clinical utility of simultaneous measurement of AFP and DCP for the early detection of HCC in China. They are predominantly used for cases caused by HBV infection. Additional large-scale prospective studies should be conducted to establish the utility of these biomarkers. PMID:27438343

  11. Evaluation methods for pretransplant oncologic markers and their prognostic impacts in patient undergoing living donor liver transplantation for hepatocellular carcinoma.

    PubMed

    Shindoh, Junichi; Sugawara, Yasuhiko; Nagata, Rihito; Kaneko, Junichi; Tamura, Sumihito; Aoki, Taku; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Tanaka, Tomohiro; Kokudo, Norihiro

    2014-04-01

    Tumor markers [alpha-fetoprotein (AFP) or des-gamma-carboxyprothrombin (DCP)] and neutrophil/lymphocyte ratio (NLR) reportedly correlate with long-term outcomes for hepatocellular carcinoma (HCC). However, no standardized method has been established for evaluating the pretransplant data. One hundred and twenty-four patients who underwent living donor liver transplantation (LDLT) were retrospectively reviewed. The best predictive parameters for tumor recurrence were maximum values for AFP or DCP and 90-day mean values for NLR, respectively, and multivariate analysis confirmed these values were correlated with tumor recurrence. However, receiver operating characteristic analysis revealed that discriminative powers were sufficient only in maximum AFP [area under the curve (AUC) 0.88, P < 0.001] and maximum DCP (AUC 0.76, P < 0.001), while mean NLR was less predictive (AUC 0.62, P = 0.20). When incorporating AFP and DCP to the Tokyo criteria (≤5 tumors with each tumor ≤ 5 cm), the presence of at least two of the following factors: (i) beyond the Tokyo criteria, (ii) AFP>250 ng/ml, and (iii) DCP > 450 mAu/ml (>450 ng/ml), was correlated with a worse 5-year disease-free survival rate (20.0% vs. 96.8%, P < 0.001) and 5-year overall survival rate (20.0% vs. 84.0%, P < 0.001). The prognosis of patients undergoing LDLT for HCC strongly relies on maximum AFP or DCP values before transplantation, while the prognostic impact of NLR is limited. PMID:24472068

  12. Pancreatic cancer stem cells

    PubMed Central

    Zhu, Ya-Yun; Yuan, Zhou

    2015-01-01

    Studies are emerging in support of the cancer stem cells (CSCs) theory which considers that a tiny subset of cancer cells is exclusively responsible for the initiation and malignant behavior of a cancer. This cell population, also termed CSCs, possesses the capacity both to self-renew, producing progeny that have the identical tumorigenic potential, and to differentiate into the bulk of cancer cells, helping serve the formation of the tumor entities, which, altogether, build the hierarchically organized structure of a cancer. In this review, we try to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic CSCs, and in the wake of which, we seek to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever. PMID:26045976

  13. Modular stems in DDH.

    PubMed

    Benazzo, F; Cuzzocrea, F; Stroppa, S; Ravasi, F; Dalla Pria, P

    2007-01-01

    The Modulus (Lima-Lto) system has been created on the association of a conical stem and a modular neck in order to address the so called "difficult hip". Modularity can maximize the options for a correct reconstruction in a total hip replacement of the coxofemoral anatomy as well as biomechanics. Modulus should be used in CDH, primary hip arthritis, the sequelae of osteotomies and in each case in which we face a congenital or acquired hip deformity. The Modulus stem has been commonly utilised in association with the Delta cup (Lima-Lto) with the chance to use big diameter heads (32-36 mm) and ceramic on ceramic coupling. Modulus has been used in association with Delta cup since November 2002. 51 patients affected by CDH have been treated. Clinical and radiographic results can be considered very good. The average evaluation based on Merle D'Aubigné schedule is equal to 17.5 with a significant increase in the results with respect to the preoperatory score (with an average score equal to 10). In the light of the above, Modulus should be considered a valuable system to optimize the results of total hip replacement also in those more complex situations with a modified femoral morphology, allowing the restoration of a normal biomechanics in terms of off-set and anteversion with benefit in terms of stability and length of the implant as well as in terms of satisfaction of the patient as far as limb length and ROM are concerned. The association of Modulus with big diameter heads gives a higher guarantee in terms of duration of the implant and restoration of the functionality in young patients with a serious deformity and increased functional demands.

  14. [Stem cells and cardiac regeneration].

    PubMed

    Perez Millan, Maria Ines; Lorenti, Alicia

    2006-01-01

    Stem cells are defined by virtue of their functional attributes: absence of tissue specific differentitated markers, capable of proliferation, able to self-maintain the population, able to produce a large number of differentiated, functional progeny, able to regenerate the tissue after injury. Cell therapy is an alternative for the treatment of several diseases, like cardiac diseases (cell cardiomyoplasty). A variety of stem cells could be used for cardiac repair: from cardiac and extracardiac sources. Each cell type has its own profile of advantages, limitations, and practicability issues in specific clinical settings. Differentiation of bone marrow stem cells to cardiomyocyte-like cells have been observed under different culture conditions. The presence of resident cardiac stem cell population capable of differentiation into cardiomyocyte or vascular lineage suggests that these cells could be used for cardiac tissue repair, and represent a great promise for clinical application. Stem cells mobilization by cytokines may also offer a strategy for cardiac regeneration. The use of stem cells (embryonic and adult) may hold the key to replacing cells lost in many devastating diseases. This potential benefit is a major focus for stem cell research.

  15. Adult Stem and Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Geraerts, Martine; Verfaillie, Catherine M.

    The discovery of adult stem cells in most adult tissues is the basis of a number of clinical studies that are carried out, with therapeutic use of hematopoietic stem cells as a prime example. Intense scientific debate is still ongoing as to whether adult stem cells may have a greater plasticity than previously thought. Although cells with some features of embryonic stem cells that, among others, express Oct4, Nanog and SSEA1 are isolated from fresh tissue, it is not clear if the greater differentiation potential is acquired during cell culture. Moreover, adult more pluripotent cells do not have all pluripotent characteristics typical for embryonic stem cells. Recently, some elegant studies were published in which adult cells could be completely reprogrammed to embryonic stem cell-like cells by overexpression of some key transcription factors for pluripotency (Oct4, Sox2, Klf4 and c-Myc). It will be interesting for the future to investigate the exact mechanisms underlying this reprogramming and whether similar transcription factor pathways are present and/or can be activated in adult more pluripotent stem cells.

  16. The new stem cell biology.

    PubMed Central

    Quesenberry, Peter J.; Colvin, Gerald A.; Lambert, Jean-Francois; Frimberger, Angela E.; Dooner, Mark S.; Mcauliffe, Christina I.; Miller, Caroline; Becker, Pamela; Badiavas, Evangelis; Falanga, Vincent J.; Elfenbein, Gerald; Lum, Lawrence G.

    2002-01-01

    Recent studies have indicated that bone marrow stem cells are capable of generating muscle, cardiac, hepatic, renal, and bone cells. Purified hematopoietic stem cells have generated cardiac and hepatic cells and reversed disease manifestations in these tissues. Hematopoietic stem cells also alter phenotype with cell cycle transit or circadian phase. During a cytokine stimulated cell cycle transit, reversible alterations of differentiation and engraftment occur. Primitive hematopoietic stem cells express a wide variety of adhesion and cytokine receptors and respond quickly with migration and podia extensions on exposure to cytokines. These data suggest an "Open Chromatin" model of stem cell regulation in which there is a fluctuating continuum in the stem cell/progenitor cell compartments, rather than a hierarchical relationship. These observations, along with progress in using low dose treatments and tolerization approaches, suggest many new therapeutic strategies involving stem cells and the creation of a new medical specialty; stemology. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:12053709

  17. Keratinocyte stem cells: a commentary.

    PubMed

    Potten, Christopher S; Booth, Catherine

    2002-10-01

    For many years it has been widely accepted that stem cells play a crucial role in adult tissue maintenance. The concept that the renewing tissues of the body contain a small subcompartment of self-maintaining stem cells, upon which the entire tissue is dependent, is also now accepted as applicable to all renewing tissues. Gene therapy and tissue engineering are driving considerable interest in the clinical application of such hierarchically organized cellular compartments. Recent initial observations have provided a tantalizing insight into the large pluripotency of these cells. Indeed, scientists are now beginning to talk about the possible totipotency of some adult tissue stem cells. Such work is currently phenomenologic, but analysis of data derived from genomics and proteomics, identifying the crucial control signals involved, will soon provide a further impetus to stem cell biology with far reaching applications. The epidermis with its relatively simple structure, ease of accessibility, and the ability to grow its cells in vitro is one obvious target tissue for testing stem cell manipulation theories. It is crucial, however, that the normal keratinocyte stem cell is thoroughly characterized prior to attempting to manipulate its pluripotency. This commentary assesses the data generated to date and critically discusses the conclusions that have been drawn. Our current level of understanding, or lack of understanding, of the keratinocyte stem cell is reviewed.

  18. Stem cells in pharmaceutical biotechnology.

    PubMed

    Zuba-Surma, Ewa K; Józkowicz, Alicja; Dulak, Józef

    2011-11-01

    Multiple populations of stem cells have been indicated to potentially participate in regeneration of injured organs. Especially, embryonic stem cells (ESC) and recently inducible pluripotent stem cells (iPS) receive a marked attention from scientists and clinicians for regenerative medicine because of their high proliferative and differentiation capacities. Despite that ESC and iPS cells are expected to give rise into multiple regenerative applications when their side effects are overcame during appropriate preparation procedures, in fact their most recent application of human ESC may, however, reside in their use as a tool in drug development and disease modeling. This review focuses on the applications of stem cells in pharmaceutical biotechnology. We discuss possible relevance of pluripotent cell stem populations in developing physiological models for any human tissue cell type useful for pharmacological, metabolic and toxicity evaluation necessary in the earliest steps of drug development. The present models applied for preclinical drug testing consist of primary cells or immortalized cell lines that show limitations in terms of accessibility or relevance to their in vivo counterparts. The availability of renewable human cells with functional similarities to their in vivo counterparts is the first landmark for a new generation of cell-based assays. We discuss the approaches for using stem cells as valuable physiological targets of drug activity which may increase the strength of target validation and efficacy potentially resulting in introducing new safer remedies into clinical trials and the marketplace. Moreover, we discuss the possible applications of stem cells for elucidating mechanisms of disease pathogenesis. The knowledge about the mechanisms governing the development and progression of multitude disorders which would come from the cellular models established based on stem cells, may give rise to new therapeutical strategies for such diseases. All

  19. Harvesting dental stem cells - Overview

    PubMed Central

    Sunil, P. M.; Manikandan, Ramanathan; Muthumurugan; Yoithapprabhunath, Thukanayakanpalayam Ragunathan; Sivakumar, Muniapillai

    2015-01-01

    Dental stem cells have recently become one of the widely researched areas in dentistry. Ever since the identification of stem cells from various dental tissues like deciduous teeth, dental papilla, periodontal ligament and third molars, storing them for future use for various clinical applications was being explored. Dental stem cells were harvested and isolated using various techniques by different investigators and laboratories. This article explains the technical aspects of preparing the patient, atraumatic and aseptic removal of the tooth and its safe transportation and preservation for future expansion. PMID:26538883

  20. Stem cells, dot-com.

    PubMed

    Liang, Bryan A; Mackey, Tim K

    2012-09-12

    Direct-to-consumer (DTC) advertising of suspect goods and services has burgeoned because of the Internet. Despite very limited approval for use, DTC stem cell-marketed "treatments" have emerged for an array of conditions, creating global public health and safety risks. However, it remains unclear whether such use of stem cells is subject to drugs or biologics regulations. To address this gap, regulatory agencies should be given clear authority, and the international community should create a framework for appropriate stem cell use. In addition, consumer protection laws should be used to scrutinize providers.

  1. Bone regeneration and stem cells

    PubMed Central

    Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

    2011-01-01

    Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

  2. 30 CFR 75.1322 - Stemming boreholes

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Stemming boreholes 75.1322 Section 75.1322... MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Explosives and Blasting § 75.1322 Stemming boreholes (a) Only noncombustible material shall be used for stemming boreholes. (b) Stemming materials other...

  3. 30 CFR 75.1322 - Stemming boreholes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Stemming boreholes. 75.1322 Section 75.1322... MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Explosives and Blasting § 75.1322 Stemming boreholes. (a) Only noncombustible material shall be used for stemming boreholes. (b) Stemming materials other...

  4. 7 CFR 29.6039 - Stem rot.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Stem rot. 29.6039 Section 29.6039 Agriculture... INSPECTION Standards Definitions § 29.6039 Stem rot. The deterioration of an uncured or frozen stem resulting from bacterial action. Although stem rot results from bacterial action, it is inactive in cured...

  5. 30 CFR 75.1322 - Stemming boreholes

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Stemming boreholes 75.1322 Section 75.1322... MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Explosives and Blasting § 75.1322 Stemming boreholes (a) Only noncombustible material shall be used for stemming boreholes. (b) Stemming materials other...

  6. 7 CFR 29.6039 - Stem rot.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Stem rot. 29.6039 Section 29.6039 Agriculture... INSPECTION Standards Definitions § 29.6039 Stem rot. The deterioration of an uncured or frozen stem resulting from bacterial action. Although stem rot results from bacterial action, it is inactive in cured...

  7. 30 CFR 75.1322 - Stemming boreholes

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Stemming boreholes 75.1322 Section 75.1322... MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Explosives and Blasting § 75.1322 Stemming boreholes (a) Only noncombustible material shall be used for stemming boreholes. (b) Stemming materials other...

  8. 30 CFR 75.1322 - Stemming boreholes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Stemming boreholes. 75.1322 Section 75.1322... MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Explosives and Blasting § 75.1322 Stemming boreholes. (a) Only noncombustible material shall be used for stemming boreholes. (b) Stemming materials other...

  9. 7 CFR 29.6039 - Stem rot.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Stem rot. 29.6039 Section 29.6039 Agriculture... INSPECTION Standards Definitions § 29.6039 Stem rot. The deterioration of an uncured or frozen stem resulting from bacterial action. Although stem rot results from bacterial action, it is inactive in cured...

  10. 7 CFR 29.6039 - Stem rot.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Stem rot. 29.6039 Section 29.6039 Agriculture... INSPECTION Standards Definitions § 29.6039 Stem rot. The deterioration of an uncured or frozen stem resulting from bacterial action. Although stem rot results from bacterial action, it is inactive in cured...

  11. The Current Status of STEM Education Research

    ERIC Educational Resources Information Center

    Brown, Josh

    2012-01-01

    This paper explores the current Science, Technology, Engineering and Mathematics (STEM) education research base through an analysis of articles from eight journals focused on the STEM disciplines. Analyzed are both practitioner and research publications to determine the current scope of STEM education research, where current STEM education…

  12. 7 CFR 29.6039 - Stem rot.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Stem rot. 29.6039 Section 29.6039 Agriculture... INSPECTION Standards Definitions § 29.6039 Stem rot. The deterioration of an uncured or frozen stem resulting from bacterial action. Although stem rot results from bacterial action, it is inactive in cured...

  13. Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines

    PubMed Central

    Ghosheh, Nidal; Olsson, Björn; Edsbagge, Josefina; Küppers-Munther, Barbara; Van Giezen, Mariska; Asplund, Annika; Andersson, Tommy B.; Björquist, Petter; Carén, Helena; Simonsson, Stina; Sartipy, Peter; Synnergren, Jane

    2016-01-01

    Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models. PMID:26949401

  14. RNA transcripts for the quantification of differentiation allow marked improvements in the performance of embryonic stem cell test (EST).

    PubMed

    Romero, Andrea C; Del Río, Eva; Vilanova, Eugenio; Sogorb, Miguel A

    2015-11-01

    Embryonic stem cell test (EST) is an in vitro validated assay for testing embryotoxicity. The EST needs improvements before being used for regulatory purposes, but also needs technical simplification for use in high throughput screenings. We propose the quantification in alterations of the differentiation of D3 monolayer cells cultures through the expression of biomarker genes in a shorter (5-day) and technically simpler (we use only monolayer cultures) test. We have defined a set of sixteen different genes biomarkers of ectoderm (Nrcam, Nes, Shh and Pnpla6), endoderm formation (Flk1 and Afp), mesoderm formation (Mesp1, Vegfa, Myo1e and Hdac7) and general cellular processes (Cdk1, Myc, Jun, Mixl, Cer and Wnt3). These, together with alterations in the viability of D3 and 3T3 cells and the prediction model of a classic EST, enhance the features of EST determinations to 100% concordance between in vivo-in vitro predictions with a set of seven different chemicals used in the validation of a classic EST. In conclusion, the proposed changes implemented in the classic EST confer it more reliability, speed and technical simplicity, which brings the EST closer to high throughput processes and regulatory purposes.

  15. Clinicopathological risk factors for recurrence within one year after initial hepatectomy for hepatocellular carcinoma.

    PubMed

    Hayashi, Michihiro; Shimizu, Tetsunosuke; Hirokawa, Fumitoshi; Inoue, Yoshihiro; Komeda, Koji; Asakuma, Mitsuhiro; Miyamoto, Yoshiharu; Takeshita, Atsushi; Shibayama, Yuro; Tanigawa, Nobuhiko

    2011-05-01

    Hepatocellular carcinoma (HCC) shows a high rate of recurrence after hepatectomy; predictive factors for early recurrence would help determine optimal therapeutic and management strategies. Among 163 patients with HCC undergoing hepatectomy with curative intent, 46 patients developed recurrence within 1 year. Clinicopathological data were retrospectively analyzed to identify predictive parameters for early recurrence. Survival rates in cases of recurrence within 1 year were worse than those of no recurrence within 1 year or recurrence after 1 year. Protein induced by vitamin K absence/antagonist II (PIVKA-II) greater than 150, positive fucosylated alpha-fetoprotein (L3-AFP), and deviancy from Milan criteria (MC) on preoperative imaging were associated with high risk of early recurrence and total number of these three risk factors predicted the survival. With multivariate analysis, (1) preoperatively, positive factors of two or more among three items of PIVKA-II, L3-AFP, and deviancy from MC; (2) and postoperatively, pathological cancer spread (microscopic vascular invasion and/or intrahepatic metastasis) both represented risks for early recurrence. A combination of three preoperative factors, PIVKA-II, L3-AFP, and MC status, in conjunction with the postoperative factor of cancer spread status represents a significant indicator for recurrence within 1 year. Improving the prognosis of patients with HCC would depend on how to adequately treat those at high risk of early recurrence.

  16. Role of Triton X-100 in chemiluminescent enzyme immunoassays capable of diagnosing genetic disorders.

    PubMed

    Chong, Richard; Rho, Jee-Eun R; Yoon, Hye-Joo; Park, Paul S; Rho, Tae-Ho D; Park, Jee Y; Park, Lucienne; Kim, Young-Hwan; Lee, Ji Hoon

    2013-11-15

    The use of Triton X surfactants in developing 1,1'-oxalylimidazole chemiluminescent enzyme immunoassays (ODI CEIs) with extended linear response range for the quantification of unconjugated estriol (uE3), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) is reported for the first time. The wider linear dynamic range in ODI CLEIA results from Triton X series (e.g., Triton X-100, -114, -405, -705) acting as an inhibitor in the interaction between Amplex Red (hydrophobic substrate) and horseradish peroxidase (hydrophilic enzyme) to produce resorufin (hydrophobic fluorescent dye). Triton X-100 acts as the appropriate inhibitor in ODI CLEIA. The maximum concentrations of AFP and hCG quantified with sandwich ODI CLEIA in the presence of Triton X-100 were 8 times higher than when analyzed with the same system in the absence of Triton X-100. In addition, the lowest concentration of uE3 determined using competitive ODI CLEIA in the presence of Triton X-100 was 20 times lower than that measured with competitive ODI CLEIA in the absence of Triton X-100. These results indicate that rapid quantification of AFP, uE3, and hCG using cost effective and highly sensitive ODI CLEIAs in the presence of Triton X-100 can be applied as an accurate, precise, and reproducible method to diagnose genetic disorders (e.g., trisomy 18 and trisomy 21) in fetuses.

  17. Reduced inflammation and improved airway expression using helper-dependent adenoviral vectors with a K18 promoter.

    PubMed

    Toietta, Gabriele; Koehler, David R; Finegold, Milton J; Lee, Brendan; Hu, Jim; Beaudet, Arthur L

    2003-05-01

    Efforts have been made to deliver transgenes to the airway epithelia of laboratory animals and humans to develop gene therapy for cystic fibrosis. These investigations have been disappointing due to combinations of transient and low-level gene expression, acute toxicity, and inflammation. We have developed new helper-dependent adenoviral vectors to deliver an epithelial cell-specific keratin 18 expression cassette driving the beta-galactosidase (beta-gal) or human alpha-fetoprotein (AFP) reporter genes. Following intranasal administration to mice, we found that the reporter genes were widely expressed in airway epithelial and submucosal cells, and secreted human AFP was also detectable in serum. In contrast to a first-generation adenoviral vector, inflammation was negligible at doses providing efficient transduction, and expression lasted longer than typically reported-up to 28 days with beta-gal and up to 15 weeks with human AFP. These results suggest that delivery to the airway of helper-dependent adenoviral vectors utilizing a tissue-specific promoter could be a significant advance in the development of gene therapy for cystic fibrosis. PMID:12718908

  18. Contamination of salvaged maternal blood by amniotic fluid and fetal red cells during elective Caesarean section

    PubMed Central

    Sullivan, I.; Faulds, J.; Ralph, C.

    2008-01-01

    Background Cell salvage in obstetrics is still a controversial subject and has yet to be fully embraced. The aim of this exploratory study was to measure amniotic fluid (AF), heparin, and fetal red cell contamination of washed filtered salvaged maternal blood and to investigate differences based on the number of suction devices used. Methods Patients undergoing elective Caesarean section were assigned alternately to one of two groups. In Group 1, all blood and AF was collected with one suction. In Group 2, AF was aspirated to waste with a second separate suction device before collection of any blood. Results In both groups, alpha-fetoprotein (AFP), squames cells, and heparin were significantly reduced (P<0.001) by the washing and filtering process. Mean AFP levels post-filtration were 2.58 IU ml−1 in Group 1 and 3.53 IU ml−1 in Group 2. Squames cells were completely removed in all but two cases. Fetal red blood cells were still present in the final product, range 0.13–4.35%. In Group 1, haemoglobin and haematocrit were higher than in Group 2, with lower white blood cell, AFP, and fetal red cell counts. Conclusions This study adds to the growing body of evidence that there is little or no possibility for AF contamination to enter the re-infusion system when used in conjunction with a leucodepletion filter. PMID:18515817

  19. Experience of a Single Center in NTBC Use in Management of Hereditary Tyrosinemia Type I in Libya

    PubMed Central

    Alobaidy, Hanna; Barkaoui, Emna

    2015-01-01

    Background: Hereditary Tyrosinemia type I (HTI) is a metabolic disease caused by deficiency of fumarylacetoacetate hydrolase enzyme. Objectives: This study reports beside its clinical and biochemical presentation, the outcome of NTBC [2- (2-nitro-4-trifloro-methylbenzoyl)-1, 3-cyclohexanedion] treatment of the disease and evaluates its biochemical markers in 16 pediatric Libyan patients. Patients and Methods: The diagnosis was based on presence of high tyrosine levels in blood and succinylacetone in urine. Results: The consanguinity rate was 81.2%, the median age at onset, at diagnosis and at starting treatment were 4.5, 8, and 9.5 months respectively. At presentation hepatomegaly, jaundice, rickets and high gamma glutamyl transferase (GGT) were observed in 87.5% of patients. All patients had extremely high alpha fetoprotein (AFP) and high alkaline phosphatase (ALP) levels. Fifteen patients were treated with NTBC, normalization of PT (Prothrombine time) was achieved in average in 14 days. The other biochemical parameters of liver function (transaminases, GGT, ALP, bilirubin and albumin) took longer to improve and several months to be normalized. Survival rate with NTBC was 86.6%. Patients who started treatment in a median of 3 months post onset observed a fast drop of AFP in 90.6% of patients (P = 0.003). Abnormal liver function and rickets were the common presentations, GGT was an early cholestatic sensitive test. ALP was constantly high even in asymptomatic patients. Conclusions: In HT1 a faster dropping of AFP is a marker of good prognosis. PMID:26495099

  20. Significant biomarkers for the management of hepatocellular carcinoma.

    PubMed

    Kondo, Yasuteru; Kimura, Osamu; Shimosegawa, Tooru

    2015-06-01

    Surveillance of hepatocellular carcinoma (HCC) is important for early detection. Imaging tests including computed tomography, magnetic resonance imaging and ultrasonography with or without various kinds of contrast medium are important options for detecting HCC. In addition to the imaging tests, various kinds of biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely used to detect HCC and analyze treatment response. Recently, various kinds of novel biomarkers (proteins and miRNA) have been found to predict the malignancy potential of HCC and treatment response to specific therapies. Moreover, various combinations of well-established biomarkers and novel biomarkers have been tested to improve sensitivity and specificity. In practical terms, biomarkers that can be analyzed using peripheral blood samples might be more useful than immunohistochemical techniques. It has been reported that quantification of cytokines in peripheral blood and the analysis of peripheral immune subsets could be good biomarkers for managing HCC. Here, we describe the usefulness of and update well-established and novel biomarkers for the management of HCC. PMID:25855582

  1. Predictive Factors of Downstaging of Hepatocellular Carcinoma Beyond the Milan Criteria Treated with Intra-arterial Therapies

    SciTech Connect

    Bova, Valentina; Miraglia, Roberto Maruzzelli, Luigi; Vizzini, Giovanni Battista; Luca, Angelo

    2013-04-15

    This study was designed to analyze the clinical results in patients suitable for liver transplantation with hepatocellular carcinoma (HCC) who exceeded Milan criteria, which underwent intra-arterial therapies (IAT), to determine predictive factors of successful downstaging. A total of 277 consecutive patients with cirrhosis and HCC were treated by IAT (transarterial oily chemoembolization, transarterial chemoembolization, transarterial embolization) in a single center. Eighty patients exceed the Milan criteria. Patients with infiltrative HCC, hypovascular HCC, and portal vein thrombosis were excluded, with a final study population of 48 patients. Tumor response to IAT was evaluated with CT and/or MRI according to modified RECIST criteria. Successful downstaging was defined as a reduction in the number and size of viable tumors to within the Milan criteria, and serum alpha-fetoprotein (AFP) <100 ng/mL, for at least 6 months. Nineteen patients (39 %) had their tumors successfully downstaged; 29 patients (61 %) did not. Multivariate analysis showed that AFP level <100 ng/mL and 3-year calculated survival probability using the Metroticket calculator were the only independent predictors of successful downstaging (p < 0.023 and p < 0.049 respectively). Biological characteristics of HCC as AFP levels <100 ng/mL and high 3-year calculated survival probability may predict a good response to downstage after IAT.

  2. Plasma abnormal prothrombin (PIVKA-II): a new and reliable marker for the detection of hepatocellular carcinoma.

    PubMed

    Takikawa, Y; Suzuki, K; Yamazaki, K; Goto, T; Madarame, T; Miura, Y; Yoshida, T; Kashiwabara, T; Sato, S

    1992-01-01

    We evaluated the clinical usefulness of a protein induced by vitamin K absence, antagonist-prothrombin (PIVKA-II), in detecting hepatocellular carcinoma (HCC) specifically in patients with liver cirrhosis, and the possible correlation between levels of PIVKA-II and pathological features of HCC. Plasma levels of PIVKA-II and alpha-fetoprotein (AFP) were measured in 628 patients with various diseases, including 253 with liver cirrhosis and 116 with HCC. PIVKA-II was detected (greater than or equal to 0.1 arbitrary unit/mL) in 54.3% of HCC and the concentration showed a positive correlation with the tumour size. As a screening test for the detection of HCC, PIVKA-II produced values comparable with those of AFP with a sensitivity, specificity and validity of 52.8, 98.8 and 51.6% respectively. Sixteen of 45 patients (37%) with HCC who had low AFP (less than 100 ng/mL) levels were positive for PIVKA-II. No apparent relationship, however, could be found between the levels of PIVKA-II and the aetiology or pathological findings of HCC. These results suggest that PIVKA-II can be a reliable marker for detecting HCC in patients with liver cirrhosis.

  3. Significant biomarkers for the management of hepatocellular carcinoma.

    PubMed

    Kondo, Yasuteru; Kimura, Osamu; Shimosegawa, Tooru

    2015-06-01

    Surveillance of hepatocellular carcinoma (HCC) is important for early detection. Imaging tests including computed tomography, magnetic resonance imaging and ultrasonography with or without various kinds of contrast medium are important options for detecting HCC. In addition to the imaging tests, various kinds of biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely used to detect HCC and analyze treatment response. Recently, various kinds of novel biomarkers (proteins and miRNA) have been found to predict the malignancy potential of HCC and treatment response to specific therapies. Moreover, various combinations of well-established biomarkers and novel biomarkers have been tested to improve sensitivity and specificity. In practical terms, biomarkers that can be analyzed using peripheral blood samples might be more useful than immunohistochemical techniques. It has been reported that quantification of cytokines in peripheral blood and the analysis of peripheral immune subsets could be good biomarkers for managing HCC. Here, we describe the usefulness of and update well-established and novel biomarkers for the management of HCC.

  4. Effect of antibiotics against Mycoplasma sp. on human embryonic stem cells undifferentiated status, pluripotency, cell viability and growth.

    PubMed

    Romorini, Leonardo; Riva, Diego Ariel; Blüguermann, Carolina; Videla Richardson, Guillermo Agustin; Scassa, Maria Elida; Sevlever, Gustavo Emilio; Miriuka, Santiago Gabriel

    2013-01-01

    Human embryonic stem cells (hESCs) are self-renewing pluripotent cells that can differentiate into specialized cells and hold great promise as models for human development and disease studies, cell-replacement therapies, drug discovery and in vitro cytotoxicity tests. The culture and differentiation of these cells are both complex and expensive, so it is essential to extreme aseptic conditions. hESCs are susceptible to Mycoplasma sp. infection, which is hard to detect and alters stem cell-associated properties. The purpose of this work was to evaluate the efficacy and cytotoxic effect of Plasmocin(TM) and ciprofloxacin (specific antibiotics used for Mycoplasma sp. eradication) on hESCs. Mycoplasma sp. infected HUES-5 884 (H5 884, stable hESCs H5-brachyury promoter-GFP line) cells were effectively cured with a 14 days Plasmocin(TM) 25 µg/ml treatment (curative treatment) while maintaining stemness characteristic features. Furthermore, cured H5 884 cells exhibit the same karyotype as the parental H5 line and expressed GFP, through up-regulation of brachyury promoter, at day 4 of differentiation onset. Moreover, H5 cells treated with ciprofloxacin 10 µg/ml for 14 days (mimic of curative treatment) and H5 and WA09 (H9) hESCs treated with Plasmocin(TM) 5 µg/ml (prophylactic treatment) for 5 passages retained hESCs features, as judged by the expression of stemness-related genes (TRA1-60, TRA1-81, SSEA-4, Oct-4, Nanog) at mRNA and protein levels. In addition, the presence of specific markers of the three germ layers (brachyury, Nkx2.5 and cTnT: mesoderm; AFP: endoderm; nestin and Pax-6: ectoderm) was verified in in vitro differentiated antibiotic-treated hESCs. In conclusion, we found that Plasmocin(TM) and ciprofloxacin do not affect hESCs stemness and pluripotency nor cell viability. However, curative treatments slightly diminished cell growth rate. This cytotoxic effect was reversible as cells regained normal growth rate upon antibiotic withdrawal.

  5. Advances in stem cell therapy.

    PubMed

    Pérez López, Silvia; Otero Hernández, Jesús

    2012-01-01

    Since the beginning of stem cell biology, considerable effort has been focused in the translation of scientific insights into new therapies. Cell-based assays represent a new strategy for organ and tissue repair in several pathologies. Moreover, alternative treatment strategies are urgently needed due to donor organ shortage that costs many lives every year and results in lifelong immunosuppression. At the moment, only the use of hematopoietic stem cells is considered as the standard for the treatment of malignant and genetic bone marrow disorders, being all other stem cell applications highly experimental. The present chapter tries to summarize some ongoing approaches of stem cell regenerative medicine and also introduces recent findings from published studies and trials conducted in various tissues such as skeletal muscle, liver and lung.

  6. Intestinal Stem Cells: Got Calcium?

    PubMed

    Nászai, Máté; Cordero, Julia B

    2016-02-01

    Calcium ions are well-known intracellular signalling molecules. A new study identifies local cytoplasmic calcium as a central integrator of metabolic and proliferative signals in Drosophila intestinal stem cells. PMID:26859268

  7. Microbioreactors for Stem Cell Research

    NASA Astrophysics Data System (ADS)

    Freytes, Donald O.; Vunjak-Novakovic, Gordana

    During tissue development and regeneration, stem cells respond to the entire milieu of their environment, through dynamic interactions with the surrounding cells, extracellular matrix, and cascades of molecular and physical regulatory factors. A new generation of culture systems is emerging to offer some of the biological fidelity of a whole organism within highly controllable in vitro settings and provide the cultured cells with the combinations of factors they normally encounter in vivo. There is a growing notion that such "biomimetic" systems are essential for unlocking the full potential of stem cells - for tissue regeneration as well as biological research. In this chapter, we discuss the biological principles for designing biologically inspired culture systems for stem cell research and focus on the control of stem cell microenvironment through surface patterning, microfluidics, and electrical stimulation.

  8. Concerns About STEM Education Restructure

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-05-01

    Several education experts told Eos that they generally favored some improvements in U.S. federal science, technology, engineering, and mathematics (STEM) education, but they also expressed concern about the Obama administration's proposed STEM reorganization plan as it affects the National Oceanic and Atmospheric Administration (NOAA). John Farrington, chair of the U.S. National Research Council (NRC) panel that issued a review of the NOAA education program in 2010, told Eos that he is confident that a considerable amount of thought went into this proposal to consolidate the K-12 STEM efforts, that consolidation could make for greater efficiencies, and that a positive aspect of having the Department of Education (ED) as a lead is that STEM education should not be considered as separate from the education of the student as a whole.

  9. Stem cells and combinatorial science.

    PubMed

    Fang, Yue Qin; Wong, Wan Qing; Yap, Yan Wen; Orner, Brendan P

    2007-09-01

    Stem cell-based technologies have the potential to help cure a number of cell degenerative diseases. Combinatorial and high throughput screening techniques could provide tools to control and manipulate the self-renewal and differentiation of stem cells. This review chronicles historic and recent progress in the stem cell field involving both pluripotent and multipotent cells, and it highlights relevant cellular signal transduction pathways. This review further describes screens using libraries of soluble, small-molecule ligands, and arrays of molecules immobilized onto surfaces while proposing future trends in similar studies. It is hoped that by reviewing both the stem cell and the relevant high throughput screening literature, this paper can act as a resource to the combinatorial science community.

  10. Three-dimentional growth of liver / stem cells in vitro under simulated microgravity

    NASA Astrophysics Data System (ADS)

    Feng, Mei Fu

    Liver is a important and largest parenchymatous organ in vivo, and have complex and diverse structures and functions. In the world, there are many peoples suffers from liver injury and dis-ease, especially in Asia, but serious shortage of donor organ, especially for organic pathological changes, is a big problem in the world. Stem cells have the capabilities to self-renew and differ-entiate into multiple lineages, and are very significant in both theoretical research and clinical applications. Compared with traditional cell culture, cells of 3D growth are more close to their situation in vivo. The specific physics environment in space provides a great opportunity for 3D growth of cells and tissues. Due to the chance for entering into the space is so scarce, to mimic microgravity effects using a rotating cell culture system (RCCS) designed by NASA, and some other methods were studied for cellular 3D growth in vitro. Neonatal mouse liver Cells, hepatic progenitor/stem cells from fetal liver and WB-F344 cells were cultured in a 1:1 mixture of DMEM and F-12 supplemented with 10 % FCS and several factors, and seeded into the RCCS, 6-well and 24-well plates. Their growth characteristic, metabolism, differentiation and gene expression were studied by SEM, Histochemistry, Flow Cytometry, RT-PCR and so on. The results showed: 1. Neonatal mouse liver Cells (1day after birth) seem easy to grow for a three-dimentional-like structure, when the cells were cultured in the RCCS, a cell aggregate formed after 1 day of culture and were kept during 10 days culture. The size of aggregate was about 1 2 mm in diameter. 2. Hepatic progenitor/stem cells from fetal liver seem a good cell resource for liver disease'cell therapy. They expressed AFP and CKs, and no mature hepato-cytes marker and bile duct epithelial cells marker were detected. When were transplanted into Nod-Scid mice, they had multi-potential differentiation. 3. WB-F344 cells, a liver epithelial cell line, could grew well on

  11. Interpreting stem diameter changes

    NASA Astrophysics Data System (ADS)

    Hölttä, T.; Sevanto, S.; Nikinmaa, E.

    2009-12-01

    Detecting phloem transport in stem diameter changes Teemu Hölttä1, Sanna Sevanto2, Eero Nikinmaa1 1Department of Forest Ecology, P.O. Box 27, FIN-00014 University of Helsinki, Finland 2Department of Physics, P.O. Box 48, FIN-00014 University of Helsinki, Finland Introduction The volume of living cells and xylem conduits vary according to pressures they are subjected to. Our proposition is that the behavior of the inner bark diameter variation which cannot be explained by changes in xylem water status arise from changes in the osmotic concentration of the phloem and cambial growth. Materials and methods Simultaneous xylem and stem diameter measurements were conducted between June 28th to October 4th 2006 in Southern Finland on a 47-year old, 15 meter tall, Scots pine tree (DBH 15 cm) at heights of 1.5 and 10 meters. The difference between the measured inner bark diameter and the inner bark diameter predicted from xylem diameter change with a simple model (assuming there was no change in the osmotic concentration of the phloem) is hypothesized to give the changes in the osmotic concentration of the inner bark. The simple model calculates the radial water exchange between the xylem and phloem driven by the water potential changes in the xylem. Results and Discussion The major signal in the inner bark diameter was the transpiration rate as assumed, but also a signal arising from the change in the osmotic concentration (Fig 1a). The predicted osmotic concentration of the phloem typically increased during the afternoon due to the loading of photosynthesized sugars to the phloem. Inner bark osmotic concentration followed the photosynthesis rate with a 3 and 4 hour time-lag at the top and base, respectively (Fig 1b). The connection between photosynthesis and the predicted change in phloem osmotic concentration was stronger in the upper part of the tree compared to lower part. The changes in the predicted osmotic concentration were not similar every day, indicating that

  12. The embryonic stem cell test.

    PubMed

    Schulpen, Sjors H W; Piersma, Aldert H

    2013-01-01

    The embryonic stem cell test is an animal-free alternative test method for developmental toxicity. Mouse embryonic stem cells are cultured in a hanging drop method to form embryoid bodies. These embryoid bodies, when plated on tissue culture dishes, differentiate to form contracting myocardial cell foci within 10 days. Inhibition of cardiomyocyte differentiation by test compounds serves as the end point of the assay, as monitored by counting contracting muscle foci under the microscope.

  13. Drosophila's contribution to stem cell research

    PubMed Central

    Singh, Gyanesh

    2016-01-01

    The discovery of Drosophila stem cells with striking similarities to mammalian stem cells has brought new hope for stem cell research. Recent developments in Drosophila stem cell research is bringing wider opportunities for contemporary stem cell biologists. In this regard, Drosophila germ cells are becoming a popular model of stem cell research. In several cases, genes that controlled Drosophila stem cells were later discovered to have functional homologs in mammalian stem cells. Like mammals, Drosophila germline stem cells (GSCs) are controlled by both intrinsic as well as external signals. Inside the Drosophila testes, germline and somatic stem cells form a cluster of cells (the hub). Hub cells depend on JAK-STAT signaling, and, in absence of this signal, they do not self-renew. In Drosophila, significant changes occur within the stem cell niche that contributes to a decline in stem cell number over time. In case of aging Drosophila, somatic niche cells show reduced DE-cadherin and unpaired (Upd) proteins. Unpaired proteins are known to directly decrease stem cell number within the niches, and, overexpression of upd within niche cells restored GSCs in older males also . Stem cells in the midgut of Drosophila are also very promising. Reduced Notch signaling was found to increase the number of midgut progenitor cells. On the other hand, activation of the Notch pathway decreased proliferation of these cells. Further research in this area should lead to the discovery of additional factors that regulate stem and progenitor cells in Drosophila. PMID:26180635

  14. Drosophila's contribution to stem cell research.

    PubMed

    Singh, Gyanesh

    2015-01-01

    The discovery of Drosophila stem cells with striking similarities to mammalian stem cells has brought new hope for stem cell research. Recent developments in Drosophila stem cell research is bringing wider opportunities for contemporary stem cell biologists. In this regard, Drosophila germ cells are becoming a popular model of stem cell research. In several cases, genes that controlled Drosophila stem cells were later discovered to have functional homologs in mammalian stem cells. Like mammals, Drosophila germline stem cells (GSCs) are controlled by both intrinsic as well as external signals. Inside the Drosophila testes, germline and somatic stem cells form a cluster of cells (the hub). Hub cells depend on JAK-STAT signaling, and, in absence of this signal, they do not self-renew. In Drosophila, significant changes occur within the stem cell niche that contributes to a decline in stem cell number over time. In case of aging Drosophila, somatic niche cells show reduced DE-cadherin and unpaired (Upd) proteins. Unpaired proteins are known to directly decrease stem cell number within the niches, and, overexpression of upd within niche cells restored GSCs in older males also . Stem cells in the midgut of Drosophila are also very promising. Reduced Notch signaling was found to increase the number of midgut progenitor cells. On the other hand, activation of the Notch pathway decreased proliferation of these cells. Further research in this area should lead to the discovery of additional factors that regulate stem and progenitor cells in Drosophila. PMID:26180635

  15. Diabetes and stem cell function.

    PubMed

    Fujimaki, Shin; Wakabayashi, Tamami; Takemasa, Tohru; Asashima, Makoto; Kuwabara, Tomoko

    2015-01-01

    Diabetes mellitus is one of the most common serious metabolic diseases that results in hyperglycemia due to defects of insulin secretion or insulin action or both. The present review focuses on the alterations to the diabetic neuronal tissues and skeletal muscle, including stem cells in both tissues, and the preventive effects of physical activity on diabetes. Diabetes is associated with various nervous disorders, such as cognitive deficits, depression, and Alzheimer's disease, and that may be caused by neural stem cell dysfunction. Additionally, diabetes induces skeletal muscle atrophy, the impairment of energy metabolism, and muscle weakness. Similar to neural stem cells, the proliferation and differentiation are attenuated in skeletal muscle stem cells, termed satellite cells. However, physical activity is very useful for preventing the diabetic alteration to the neuronal tissues and skeletal muscle. Physical activity improves neurogenic capacity of neural stem cells and the proliferative and differentiative abilities of satellite cells. The present review proposes physical activity as a useful measure for the patients in diabetes to improve the physiological functions and to maintain their quality of life. It further discusses the use of stem cell-based approaches in the context of diabetes treatment.

  16. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    PubMed

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

  17. Improvement of mesenchymal stem cell differentiation into the endoderm lineage by four step sequential method in biocompatible biomaterial

    PubMed Central

    Azandeh, Saeed; Mohammad Gharravi, Anneh; Orazizadeh, Mahmoud; Khodadi, Ali; Hashemi Tabar, Mahmoud

    2016-01-01

    Introduction: The goal of the study described here, was to investigate the potential of umbilical cord derived mesenchymal stem cell (UC-MSCs) into hepatocyte like cells in a sequential 2D and 3D differentiation protocols as alternative therapy. Methods: Mesenchymal stem cells (MSCs) were isolated from the umbilical cord (UC) and CD markers were analyzed by flow cytometry. For hepatic differentiation of UC-MSCs, cells were induced with a sequential 4-step protocol in 3D and 2D culture system. Urea concentration and albumin secretion into the culture medium was quantified by ELISA. Gene expression levels of AFP, ALB, and CK18 were determined by RT-PCR. Data were statistically analyzed by the SPSS software. The difference between the mean was considered significant when p < 0.05. Results: Growth factor dependent morphological changes from elongated fibroblast-like cells to round epithelial cell morphology were observed in 2D culture. Cell proliferation analysis showed round-shaped morphology with clear cytoplasm and nucleus on the alginate scaffold in 3D culture. The mean valuses of albumin production and urea secretion were significantly higher in the 3D Culture system when compared with the 2D culture (p = 0.005 vs p = 0.001), respectively. Treatment of cells with TSA in the final step of differentiation induced an increased expression of CK18 and a decreased expression of αFP in both the 3D and 2D cultures (p = 0.026), but led to a decreased albumin gene expression, and an increased expression in the 2D culture (p = 0.001). Conclusion: Findings of the present study indicated that sequential exposure of UC-MSCs with growth factors in 3D culture improves hepatic differentiation. PMID:27340619

  18. Collagen-IV supported embryoid bodies formation and differentiation from buffalo (Bubalus bubalis) embryonic stem cells

    SciTech Connect

    Taru Sharma, G.; Dubey, Pawan K.; Verma, Om Prakash; Pratheesh, M.D.; Nath, Amar; Sai Kumar, G.

    2012-08-03

    Graphical abstract: EBs formation, characterization and expression of germinal layers marker genes of in vivo developed teratoma using four different types of extracellular matrices. Highlights: Black-Right-Pointing-Pointer Collagen-IV matrix is found cytocompatible for EBs formation and differentiation. Black-Right-Pointing-Pointer Established 3D microenvironment for ES cells development and differentiation into three germ layers. Black-Right-Pointing-Pointer Collagen-IV may be useful as promising candidate for ES cells based therapeutic applications. -- Abstract: Embryoid bodies (EBs) are used as in vitro model to study early extraembryonic tissue formation and differentiation. In this study, a novel method using three dimensional extracellular matrices for in vitro generation of EBs from buffalo embryonic stem (ES) cells and its differentiation potential by teratoma formation was successfully established. In vitro derived inner cell masses (ICMs) of hatched buffalo blastocyst were cultured on buffalo fetal fibroblast feeder layer for primary cell colony formation. For generation of EBs, pluripotent ES cells were seeded onto four different types of extracellular matrices viz; collagen-IV, laminin, fibronectin and matrigel using undifferentiating ES cell culture medium. After 5 days of culture, ESCs gradually grew into aggregates and formed simple EBs having circular structures. Twenty-six days later, they formed cystic EBs over collagen matrix with higher EBs formation and greater proliferation rate as compared to other extracellular matrices. Studies involving histological observations, fluorescence microscopy and RT-PCR analysis of the in vivo developed teratoma revealed that presence of all the three germ layer derivatives viz. ectoderm (NCAM), mesoderm (Flk-1) and endoderm (AFP). In conclusion, the method described here demonstrates a simple and cost-effective way of generating EBs from buffalo ES cells. Collagen-IV matrix was found cytocompatible as it

  19. Cancer stem cells in hepatocellular carcinoma - an immunohistochemical study with histopathological association

    PubMed Central

    Matthai, Smita Mary; Ramakrishna, Banumathi

    2015-01-01

    Background & objectives: Cancer stem cells (CSCs) may be responsible for tumour recurrence and resistance to chemotherapy in hepatocellular carcinoma (HCC). This study was carried out to evaluate the association between histological parameters and liver CSCs (LCSC) in HCC, and to compare distribution of liver CSCs in HCC associated with and without hepatitis B virus (HBV) infection. Methods: Seventy nine tumours (49 surgical resections from 46 patients, and 30 from autopsy) were reviewed. Immunohistochemical staining for the LCSC marker EpCAM (epithelial cell adhesion molecule), liver progenitor cell (LPC) markers CK19 (cytokeratin 19) and neural cell adhesion molecule (NCAM) were performed and were associated with histological features of tumour behaviour. Results: Thirty three tumours (41.8%) showed positive staining for EpCAM. CK19 and NCAM expression were seen in 26 (32.9%) and four (5.1%) tumours, respectively. The expression of EpCAM and CK19 was significantly associated with each other (P<0.001). EpCAM expression was significantly associated with clinical and histological features indicating aggressive tumour behaviour, including younger age of onset, higher serum alpha foetoprotein (AFP) levels, tumour cell dedifferentiation, increased mitotic activity, and vascular invasiveness. There was no significant difference in expression of EpCAM, CK19 and NCAM between HBV positive and negative HCC. Interpretation & conclusions: The LCSC marker EpCAM was expressed in less than half of HCC, was independent of HBV aetiology, and was strongly associated with clinical and histological features of aggressive tumour behaviour. Positive staining for CK19 suggests a possible LPC origin of the EpCAM positive HCCs. PMID:26609030

  20. Dormancy activation mechanism of tracheal stem cells

    PubMed Central

    Li, Xin; Xu, Jing-xian; Jia, Xin-Shan; Li, Wen-ya; Han, Yi-chen; Wang, En-hua; Li, Fang

    2016-01-01

    Accurate markers and molecular mechanisms of stem cell dormancy and activation are poorly understood. In this study, the anti-cancer drug, 5-fluorouracil, was used to selectively kill proliferating cells of human bronchial epithelial (HBE) cell line. This method can enrich and purify stem cell population. The dormant versus active status of stem cells was determined by phosphorylation of RNAp II Ser2. The surviving stem cells were cultured to form stem cell spheres expressing stem cell markers and transplanted into nude mice to form a teratoma. The results demonstrated the properties of stem cells and potential for multi-directional differentiation. Bisulfite sequencing polymerase chain reaction showed that demethylation of the Sox2 promoter by 5-FU resulted in Sox2 expression in the dormant stem cells. This study shows that the dormancy and activation of HBE stem cells is closely related to epigenetic modification. PMID:27009861

  1. DNA methylation and hydroxymethylation in stem cells.

    PubMed

    Cheng, Ying; Xie, Nina; Jin, Peng; Wang, Tao

    2015-06-01

    In mammals, DNA methylation and hydroxymethylation are specific epigenetic mechanisms that can contribute to the regulation of gene expression and cellular functions. DNA methylation is important for the function of embryonic stem cells and adult stem cells (such as haematopoietic stem cells, neural stem cells and germline stem cells), and changes in DNA methylation patterns are essential for successful nuclear reprogramming. In the past several years, the rediscovery of hydroxymethylation and the TET enzymes expanded our insights tremendously and uncovered more dynamic aspects of cytosine methylation regulation. Here, we review the current knowledge and highlight the most recent advances in DNA methylation and hydroxymethylation in embryonic stem cells, induced pluripotent stem cells and several well-studied adult stems cells. Our current understanding of stem cell epigenetics and new advances in the field will undoubtedly stimulate further clinical applications of regenerative medicine in the future.

  2. Engineering stem cell niches in bioreactors

    PubMed Central

    Liu, Meimei; Liu, Ning; Zang, Ru; Li, Yan; Yang, Shang-Tian

    2013-01-01

    Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “niches”, to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/autocrine signaling and physical forces (i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering. PMID:24179601

  3. Stem cell potential of the mammalian gonad

    PubMed Central

    Liu, Chia-Feng; Barsoum, Ivraym; Gupta, Rupesh; Hofmann, Marie-Claude; Yao, Humphrey Hung-Chang

    2010-01-01

    Stem cells have enormous potential for therapeutic application because of their ability to self-renew and differentiate into different cell types. Gonads, which consist of somatic cells and germ cells, are the only organs capable of transmitting genetic materials to the offspring. Germ-line stem cells and somatic stem cells have been found in the testis; however, the presence of stem cells in the ovary remains controversial. In this review, we discuss studies focusing on whether stem cell properties are present in the different cell types of male and female gonads and their implications on stem cell research. PMID:19482665

  4. Stem cells in cardiac repair.

    PubMed

    Henning, Robert J

    2011-01-01

    Myocardial infarction is the leading cause of death among people in industrialized nations. Although the heart has some ability to regenerate after infarction, myocardial restoration is inadequate. Consequently, investigators are currently exploring the use of human embryonic stem cells (hESCs), skeletal myoblasts and adult bone marrow stem cells to limit infarct size. hESCs are pluripotent cells that can regenerate myocardium in infarcted hearts, attenuate heart remodeling and contribute to left ventricle (LV) systolic force development. Since hESCs can form heart teratomas, investigators are differentiating hESCs toward cardiac progenitor cells prior to transplantation into hearts. Large quantities of hESCs cardiac progenitor cells, however, must be generated, immune rejection must be prevented and grafts must survive over the long term to significantly improve myocardial performance. Transplanted autologous skeletal myoblasts can survive in infarcted myocardium in small numbers, proliferate, differentiate into skeletal myofibers and increase the LV ejection fraction. These cells, however, do not form electromechanical connections with host cardiomyocytes. Consequently, electrical re-entry can occur and cause cardiac arrhythmias. Autologous bone marrow mononuclear cells contain hematopoietic and mesenchymal stem cells. In several meta-analyses, patients with coronary disease who received autologous bone marrow cells by intracoronary injection show significant 3.7% (range: 1.9-5.4%) increases in LV ejection fraction, decreases in LV end-systolic volume of -4.8 ml (range: -1.4 to -8.2 ml) and reductions in infarct size of 5.5% (-1.9 to -9.1%), without experiencing arrhythmias. Bone marrow cells appear to release biologically active factors that limit myocardial damage. Unfortunately, bone marrow cells from patients with chronic diseases propagate poorly and can die prematurely. Substantial challenges must be addressed and resolved to advance the use of stem cells

  5. Targeting Breast Cancer Stem Cells

    PubMed Central

    McDermott, Sean P.; Wicha, Max S.

    2010-01-01

    The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is postulated that tissue-resident stem or progenitors are the most common targets of transformation. Clinically, CSCs are predicted to mediate tumor recurrence after chemo- and radiation-therapy due to the relative inability of these modalities to effectively target CSCs. If this is the case, then CSC must be efficiently targeted to achieve a true cure. Similarities between normal and malignant stem cells, at the levels of cell-surface proteins, molecular pathways, cell cycle quiescence, and microRNA signaling present challenges in developing CSC-specific therapeutics. Approaches to targeting CSCs include the development of agents targeting known stem cell regulatory pathways as well as unbiased high-throughput siRNA or small-molecule screening. Based on studies of pathways present in normal stem cells, recent work has identified potential “Achilles heals” of CSC, whereas unbiased screening provides opportunities to identify new pathways utilized by CSC as well as develop potential therapeutic agents. Here, we review both approaches and their potential to effectively target breast CSC. PMID:20599450

  6. Stem-cell ecology and stem cells in motion

    PubMed Central

    Scadden, David T.

    2008-01-01

    This review highlights major scientific developments over the past 50 years or so in concepts related to stem-cell ecology and to stem cells in motion. Many thorough and eloquent reviews have been presented in the last 5 years updating progress in these issues. Some paradigms have been challenged, others validated, or new ones brought to light. In the present review, we will confine our remarks to the historical development of progress. In doing so, we will refrain from a detailed analysis of controversial data, emphasizing instead widely accepted views and some challenging novel ones. PMID:18398055

  7. [Therapeutic use of stem cells. II. Adult stem cells].

    PubMed

    Uzan, Georges

    2004-09-30

    Many degenerative diseases are not curable by means of classical medicine. The long term objective of cell therapy is to treat the patients with their own stem cells that could be either purified from the diseased organ or from "reservoirs" of stem cells such as that constituted by the bone marrow. The existence of stem cells in the organs or reservoirs is now established in vitro and in some cases, in animal models. Numbers of technical problems linked to the scarcity of these cells still delay the clinical use of purified stem cells. However, clinical protocols using heterogeneous cell populations have already started to treat a growing number of diseases. In some case, autologous cells can be used, as it is the case for bone marrow transplantation in blood diseases. Mesenchymal cells, also purified from the bone marrow are currently used in orthopaedic diseases. Because these cells reveal a broad differentiation potential, active research programs explore their possible use for treatment of other diseases. Bone marrow also contains vascular stem cells that could be active in reappearing defective vessels responsible for ischaemic diseases. Indeed, clinical trials in which bone marrow cells are injected in the cardiac muscle of patients with myocardial infarction or in the leg muscle (gastrocnemius) of patients with hind limb ischaemia have already started. Artificial skin prepared from skin biopsies is used for the reconstitution of the derma of severely burned patients. Clinical trials have also started, using allogenic cells. The patients must be treated by immunosuppressive drugs. Neurodegenerative diseases such as Parkinson have been successfully treated by intra-cerebral injection of foetal neurones. Pancreatic islets implanted in the liver have shown to re-establish a normal glycaemia in diabetic patients. However, all these clinical trials use differentiated cells or at least progenitors which display differentiation potential and lifetime much more

  8. Preliminary evidence for associations between second-trimester human chorionic gonadotropin and unconjugated oestriol levels with pregnancy outcome in Down syndrome pregnancies.

    PubMed

    Benn, P A

    1998-04-01

    Fifty-six cases of Down syndrome were identified in a population of women who had undergone maternal serum triple marker screening [alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) analyses]. These affected pregnancies represented all known cases present in the population of 34,368 women screened. Using a 1:270 mid-trimester Down syndrome risk to define the screen-positive group, 42 affected pregnancies were screen-positive (medians: AFP = 0.79 MOM, hCG = 2.13 MOM, uE3 = 0.62 MOM, age 34.6 years) and 14 pregnancies were screen-negative (medians: AFP = 0.82 MOM, hCG = 1.57 MOM, uE3 = 0.92 MOM, age 24.2 years). Four affected pregnancies were associated with in utero death and each of these cases was associated with relatively extreme values of AFP, hCG, and uE3, including the three highest levels of hCG in the entire series of Down syndrome pregnancies. Twenty-nine (15 screen-positive and 14 screen-negative) affected pregnancies resulted in liveborns. Down syndrome pregnancies had a significantly shorter gestational term than controls, and Down syndrome babies were also lighter than controls, even after adjustment for sex and gestational age. In affected pregnancies, a low uE3 level appeared to be associated with a greater chance of a small-for-gestational age baby. No correlations could be demonstrated between AFP or hCG levels and gestational age-adjusted term weight. Based on this small series, it would appear that uE3 may be particularly useful in detecting those Down syndrome cases associated with small-for-gestational age fetuses. A very high hCG value may indicate a higher probability of fetal death. PMID:9602476

  9. Caveolin-1 is essential in the differentiation of human adipose-derived stem cells into hepatocyte-like cells via an MAPK pathway-dependent mechanism

    PubMed Central

    GUAN, XIN; WANG, NAN; CUI, FENGGONG; LIU, YANG; LIU, PENG; ZHAO, JINGYUAN; HAN, CHAO; LI, XIAOYAN; LENG, ZHIQIAN; LI, YING; JI, XIAOFEI; ZOU, WEI; LIU, JING

    2016-01-01

    Human adipose-derived stem cells (hADSCs), widely present in the adult human body, are an emerging and attractive tool for the establishment of stem cell-based therapies for the treatment of liver disease. However, the mechanism underlying hADSCs hepatic differentiation remains to be elucidated. Caveolin-1 (Cav-1), a 21–24 kDa membrane structural protein, is important in liver regeneration and development. In the present study, fluorescence immuno-cytochemistry and western blotting were used to analyze the expression levels of Cav-1 and evaluate its effects on the hepatic differentiation of hADSCs. The results revealed that primary hADSCs preserved the ability to proliferate and differentiate into hepatocyte-like cells. As demonstrated by semiquantitative reverse transcription-polymerase chain reaction, hepatocyte-inducing factors significantly increased the expression of Cav-1 in a time-dependent manner, as indicated by increased expression levels of the albumin (ALB) and α-fetoprotein (AFP) markers. In addition the expression levels of ALB and HNF1A significantly decreased following small interfering RNA-mediated knockdown of Cav-1. The mitogen-activated protein kinase (MAPK) signaling pathway was activated during hepatic differentiation and inhibited following Cav-1 knockdown. These results suggested that Cav-1 may regulate the hepatocyte-like differentiation of hADSCs by modulating mitogen-activated protein kinase kinase/MAPK signaling. The results of the present study will provide experimental and theoretical basis for further clinical studies on stem cell transplantation in the treatment of liver disease. PMID:26717806

  10. Stem cells sources for intervertebral disc regeneration.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-05-26

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration.

  11. Stem cells sources for intervertebral disc regeneration

    PubMed Central

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-01-01

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  12. Stem cells sources for intervertebral disc regeneration.

    PubMed

    Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luca; Loppini, Mattia; Denaro, Vincenzo

    2016-05-26

    Intervertebral disc regeneration field is rapidly growing since disc disorders represent a major health problem in industrialized countries with very few possible treatments. Indeed, current available therapies are symptomatic, and surgical procedures consist in disc removal and spinal fusion, which is not immune to regardable concerns about possible comorbidities, cost-effectiveness, secondary risks and long-lasting outcomes. This review paper aims to share recent advances in stem cell therapy for the treatment of intervertebral disc degeneration. In literature the potential use of different adult stem cells for intervertebral disc regeneration has already been reported. Bone marrow mesenchymal stromal/stem cells, adipose tissue derived stem cells, synovial stem cells, muscle-derived stem cells, olfactory neural stem cells, induced pluripotent stem cells, hematopoietic stem cells, disc stem cells, and embryonic stem cells have been studied for this purpose either in vitro or in vivo. Moreover, several engineered carriers (e.g., hydrogels), characterized by full biocompatibility and prompt biodegradation, have been designed and combined with different stem cell types in order to optimize the local and controlled delivery of cellular substrates in situ. The paper overviews the literature discussing the current status of our knowledge of the different stem cells types used as a cell-based therapy for disc regeneration. PMID:27247704

  13. ALT-GTS-Stem Fabrication

    SciTech Connect

    Thuan Nguyen

    2008-09-25

    In 2007, a study investigated options to manufacture stems utilizing methods that would replace crush form grinding while maintaining or improving quality at a comparative cost. Crush form grinding is a special process used at the Kansas City Plant to finish stem sections of reservoir products. However, crush form grinding is a complex process with many variables affecting the final product. This study identified two potential methods that can be applied to stems. Profile grinding was investigated in 2007. This project continued in 2008 proving that single point turning on a multi-turret is an option with additional benefits. It is an economical way to meet floor space limitations for our KCRIMS mission.

  14. Problematizing the STEM Pipeline Metaphor: Is the STEM Pipeline Metaphor Serving Our Students and the STEM Workforce?

    ERIC Educational Resources Information Center

    Cannady, Matthew A.; Greenwald, Eric; Harris, Kimberly N.

    2014-01-01

    Researchers and policy makers often use the metaphor of an ever-narrowing pipeline to describe the trajectory to a science, technology, engineering or mathematics (STEM) degree or career. This study interrogates the appropriateness of the STEM pipeline as the dominant frame for understanding and making policies related to STEM career trajectories.…

  15. Stem cell transplantation for neuroblastoma.

    PubMed

    Fish, J D; Grupp, S A

    2008-01-01

    High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The use of high-dose chemotherapy with autologous hematopoietic stem cell rescue in consolidation has resulted in improvements in survival, although further advances are still needed. Newer approaches to SCT and supportive care, most notably the transition to PBSC, have resulted in further improvement in survival and decreases in treatment-related mortality. Research into experimental approaches to hematopoietic SCT is ongoing.

  16. Becoming a Blood Stem Cell Donor

    MedlinePlus

    ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 359 359 Loading... ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  17. General Information about Childhood Brain Stem Glioma

    MedlinePlus

    ... Brain Stem Glioma Treatment (PDQ®)–Patient Version General Information About Childhood Brain Stem Glioma Go to Health ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  18. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  19. Adult Stem Cells and Diabetes Therapy

    PubMed Central

    Ilgun, Handenur; Kim, Joseph William; Luo, LuGuang

    2016-01-01

    The World Health Organization estimates that diabetes will be the fourth most prevalent disease by 2050. Developing a new therapy for diabetes is a challenge for researchers and clinicians in field. Many medications are being used for treatment of diabetes however with no conclusive and effective results therefore alternative therapies are required. Stem cell therapy is a promising tool for diabetes therapy, and it has involved embryonic stem cells, adult stem cells, and pluripotent stem cells. In this review, we focus on adult stem cells, especial human bone marrow stem cells (BM) for diabetes therapy, its history, and current development. We discuss prospects for future diabetes therapy such as induced pluripotent stem cells which have popularity in stem cell research area. PMID:27123495

  20. 7 CFR 30.4 - Stemmed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND STANDARDS Classification of Leaf Tobacco Covering Classes, Types and Groups of Grades § 30.4 Stemmed. A form of leaf tobacco consisting of a collection of leaves from which the stems or midribs...

  1. Stem cell technology for neurodegenerative diseases.

    PubMed

    Lunn, J Simon; Sakowski, Stacey A; Hur, Junguk; Feldman, Eva L

    2011-09-01

    Over the past 20 years, stem cell technologies have become an increasingly attractive option to investigate and treat neurodegenerative diseases. In the current review, we discuss the process of extending basic stem cell research into translational therapies for patients suffering from neurodegenerative diseases. We begin with a discussion of the burden of these diseases on society, emphasizing the need for increased attention toward advancing stem cell therapies. We then explain the various types of stem cells utilized in neurodegenerative disease research, and outline important issues to consider in the transition of stem cell therapy from bench to bedside. Finally, we detail the current progress regarding the applications of stem cell therapies to specific neurodegenerative diseases, focusing on Parkinson disease, Huntington disease, Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy. With a greater understanding of the capacity of stem cell technologies, there is growing public hope that stem cell therapies will continue to progress into realistic and efficacious treatments for neurodegenerative diseases.

  2. Making STEM Fun: How to Organize a STEM Camp

    ERIC Educational Resources Information Center

    Davis, Kimberly E. Bryant; Hardin, Stacey E.

    2013-01-01

    The work from the University of Central Florida's STEM summer camp (sponsored by Workforce Central Florida) is shared. The camps targeted low-SES schools with a high percentage of students on free and reduced lunch as well as high percentages of students with. Students were given preassessments and postassessments to gauge their knowledge of and…

  3. College Students' Conceptions of Stem Cells, Stem Cell Research, and Cloning

    ERIC Educational Resources Information Center

    Concannon, James P.; Siegel, Marcelle A.; Halverson, Kristy; Freyermuth, Sharyn

    2010-01-01

    In this study, we examined 96 undergraduate non-science majors' conceptions of stem cells, stem cell research, and cloning. This study was performed at a large, Midwest, research extensive university. Participants in the study were asked to answer 23 questions relating to stem cells, stem cell research, and cloning in an on-line assessment before…

  4. STEM-focused High Schools as a Strategy for Enhancing Readiness for Postsecondary STEM Programs

    ERIC Educational Resources Information Center

    Means, Barbara; Wang, Haiwen; Young, Viki; Peters, Vanessa L.; Lynch, Sharon J.

    2016-01-01

    The logic underlying inclusive STEM high schools (ISHSs) posits that requiring all students to take advanced college preparatory STEM courses while providing student-centered, reform-oriented instruction, ample student supports, and real-world STEM experiences and role models will prepare and inspire students admitted on the basis of STEM interest…

  5. [Genetic regulation of plant shoot stem cells].

    PubMed

    Al'bert, E V; Ezhova, T A

    2013-02-01

    This article describes the main features of plant stem cells and summarizes the results of studies of the genetic control of stem cell maintenance in the apical meristem of the shoot. It is demonstrated that the WUS-CLV gene system plays a key role in the maintenance of shoot apical stem cells and the formation of adventitious buds and somatic embryos. Unconventional concepts of plant stem cells are considered.

  6. Autophagy: a decisive process for stemness

    PubMed Central

    García-Prat, Laura

    2016-01-01

    Mature skeletal muscle is a stable tissue imposing low homeostatic demand on its stem cells, which remain in a quiescent state in their niche over time. We have shown that these long-lived resting stem cells attenuate proteotoxicity and avoid senescence through basal autophagy. This protective “clean-up” system is lost during aging, resulting in stem cell regenerative decline. Thus, autophagy is required for muscle stem cell homeostasis maintenance. PMID:26934325

  7. Stem Cell Research Policies around the World

    PubMed Central

    Dhar, Deepali; Hsi-en Ho, John

    2009-01-01

    The proliferation of stem cell research, conflated with its ethical and moral implications, has led governments to attempt regulation of both the science and funding of stem cells. Due to a diversity of opinions and cultural viewpoints, no single policy or set of rules exist to govern stem cell research. Instead, each country has developed its own policy. The following map catalogs the general legal and political milleu regarding stem cell research by country. PMID:19774124

  8. Involvement of Plant Stem Cells or Stem Cell-Like Cells in Dedifferentiation.

    PubMed

    Jiang, Fangwei; Feng, Zhenhua; Liu, Hailiang; Zhu, Jian

    2015-01-01

    Dedifferentiation is the transformation of cells from a given differentiated state to a less differentiated or stem cell-like state. Stem cell-related genes play important roles in dedifferentiation, which exhibits similar histone modification and DNA methylation features to stem cell maintenance. Hence, stem cell-related factors possibly synergistically function to provide a specific niche beneficial to dedifferentiation. During callus formation in Arabidopsis petioles, cells adjacent to procambium cells (stem cell-like cells) are dedifferentiated and survive more easily than other cell types. This finding indicates that stem cells or stem cell-like cells may influence the dedifferentiating niche. In this paper, we provide a brief overview of stem cell maintenance and dedifferentiation regulation. We also summarize current knowledge of genetic and epigenetic mechanisms underlying the balance between differentiation and dedifferentiation. Furthermore, we discuss the correlation of stem cells or stem cell-like cells with dedifferentiation. PMID:26635851

  9. Setting FIRES to Stem Cell Research

    ERIC Educational Resources Information Center

    Miller, Roxanne Grietz

    2005-01-01

    The goal of this lesson is to present the basic scientific knowledge about stem cells, the promise of stem cell research to medicine, and the ethical considerations and arguments involved. One of the challenges of discussing stem cell research is that the field is constantly evolving and the most current information changes almost daily. Few…

  10. Learning about Cancer by Studying Stem Cells

    MedlinePlus

    ... About Cancer by Studying Stem Cells Inside Life Science View All Articles | Inside Life Science Home Page Learning About Cancer by Studying Stem ... Once Upon a Stem Cell This Inside Life Science article also appears on LiveScience . Learn about related ...

  11. Understanding the STEM Pipeline. Working Paper 125

    ERIC Educational Resources Information Center

    Sass, Tim R.

    2015-01-01

    I investigate the determinants of high school completion and college attendance, the likelihood of taking science, technology, engineering or math (STEM) courses in the first year of college and the probability of earning a degree in a STEM field. The focus is on women and minorities, who tend to be underrepresented in STEM fields. Tracking four…

  12. Developing Effective STEM Professional Development Programs

    ERIC Educational Resources Information Center

    Avery, Zanj K.; Reeve, Edward M.

    2013-01-01

    To help the United States stay globally competitive in terms of innovation and invention, the teaching of science, technology, engineering, and mathematics (STEM) has become a priority in P-12 education today. As the need for students to become stronger in STEM grows, so does the need for well-qualified STEM teachers who understand what is needed…

  13. Advancing STEM Education: A 2020 Vision

    ERIC Educational Resources Information Center

    Bybee, Rodger W.

    2010-01-01

    STEM (an acronym for science, technology, engineering and mathematics) had its origins in the 1990s at the National Science Foundation (NSF) and has been used as a generic label for any event, policy, program, or practice that involves one or several of the STEM disciplines. However, a recent survey on the "perception of STEM" found that most…

  14. A State Policymaker's STEM Playbook. Promising Practices

    ERIC Educational Resources Information Center

    Zinth, Jennifer; Goetz, Tami

    2016-01-01

    Science, technology, engineering and mathematics (STEM) has captured the attention of state policymakers who are concerned about equitable access to high-quality educational experiences and preparing and inspiring students to pursue STEM careers. Yet in many states, STEM policymaking efforts have not achieved their intended return on investment…

  15. Facilitating Teaching and Learning across STEM Fields

    ERIC Educational Resources Information Center

    Ejiwale, James A.

    2012-01-01

    The reformation of the contents for instruction across STEM fields has changed the role of STEM educators from being a "dictator" in the classroom/laboratory to a facilitator of students' activities. More important, this new paradigm and professional orientation for STEM educators is no more limited to delivering instruction intuitively, but with…

  16. Who Teaches the "STE" in STEM?

    ERIC Educational Resources Information Center

    Bartholomew, Scott

    2015-01-01

    STEM (Science, Technology, Engineering, and Math) is a buzzword in America (Ames, 2013; Woodruff, 2013). With recent pushes from the federal government (Obama, 2013) the educational landscape is changing, with an increased emphasis on STEM (Noddings, 2013; Obama, 2013). However, a clear definition of who teaches each aspect of STEM does not exist…

  17. Stem cells' exodus: a journey to immortality.

    PubMed

    Zhou, Yi; Lewallen, Michelle; Xie, Ting

    2013-01-28

    Stem cell niches provide a regulatory microenvironment that retains stem cells and promotes self-renewal. Recently in Developmental Cell, Rinkevich et al. (2013) showed that cell islands (CIs) of Botryllus schlosseri, a colonial chordate, provide niches for maintaining cycling stem cells that migrate from degenerated CIs to newly formed buds.

  18. Blood-Forming Stem Cell Transplants

    MedlinePlus

    ... Health Professionals Questions to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment ... are the donor’s stem cells matched to the patient’s stem cells in allogeneic ...

  19. Human stem cell ethics: beyond the embryo.

    PubMed

    Sugarman, Jeremy

    2008-06-01

    Human embryonic stem cell research has elicited powerful debates about the morality of destroying human embryos. However, there are important ethical issues related to stem cell research that are unrelated to embryo destruction. These include particular issues involving different types of cells used, the procurement of such cells, in vivo use of stem cells, intellectual property, and conflicts of interest.

  20. The Split-Stem Technique

    ERIC Educational Resources Information Center

    Carter, Roy A.

    1972-01-01

    Describes a procedure useful for investigating the effects of substances on plant growth and development. A bean seedling's stem is partially split, and each half is placed in a different nutrient solution. Suggestions for the instructional use of the technique are made. (AL)

  1. Cancer stem cell signaling pathways.

    PubMed

    Matsui, William H

    2016-09-01

    Tissue development and homeostasis are governed by the actions of stem cells. Multipotent cells are capable of self-renewal during the course of one's lifetime. The accurate and appropriate regulation of stem cell functions is absolutely critical for normal biological activity. Several key developmental or signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the Janus-activated kinase/signal transducer and activator of transcription, Hedgehog, Wnt, Notch, phosphatidylinositol 3-kinase/phosphatase and tensin homolog, and nuclear factor-κB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. Unsurprisingly, many of these crucial signaling pathways are dysregulated in cancer. Growing evidence suggests that overactive or abnormal signaling within and among these pathways may contribute to the survival of cancer stem cells (CSCs). CSCs are a relatively rare population of cancer cells capable of self-renewal, differentiation, and generation of serially transplantable heterogeneous tumors of several types of cancer. PMID:27611937

  2. Stem cells and kidney regeneration.

    PubMed

    Chou, Yu-Hsiang; Pan, Szu-Yu; Yang, Chian-Huei; Lin, Shuei-Liong

    2014-04-01

    Kidney disease is an escalating burden all over the world. In addition to preventing kidney injury, regenerating damaged renal tissue is as important as to retard the progression of chronic kidney disease to end stage renal disease. Although the kidney is a delicate organ and has only limited regenerative capacity compared to the other organs, an increasing understanding of renal development and renal reprogramming has kindled the prospects of regenerative options for kidney disease. Here, we will review the advances in the kidney regeneration including the manipulation of renal tubular cells, fibroblasts, endothelial cells, and macrophages in renal disease. Several types of stem cells, such as bone marrow-derived cells, adipocyte-derived mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells are also applied for renal regeneration. Endogenous or lineage reprogrammed renal progenitor cells represent an attractive possibility for differentiation into multiple renal cell types. Angiogenesis can ameliorate hypoxia and renal fibrosis. Based on these studies and knowledge, we hope to innovate more reliable pharmacological or biotechnical methods for kidney regeneration medicine.

  3. STEM Equality and Diversity Toolkit

    ERIC Educational Resources Information Center

    Collins, Jill

    2011-01-01

    In 2008, the Centre for Science Education at Sheffield Hallam University teamed up with VT Enterprise (now Babcock International) in their submission of a successful bid to deliver the national STEM (Science, Technology, Engineering and Maths) Subject Choice and Careers Project. An integral part of the bid was the promotion of equality and…

  4. Stem Cells and Liver Regeneration

    PubMed Central

    DUNCAN, ANDREW W.; DORRELL, CRAIG; GROMPE, MARKUS

    2011-01-01

    One of the defining features of the liver is the capacity to maintain a constant size despite injury. Although the precise molecular signals involved in the maintenance of liver size are not completely known, it is clear that the liver delicately balances regeneration with overgrowth. Mammals, for example, can survive surgical removal of up to 75% of the total liver mass. Within 1 week after liver resection, the total number of liver cells is restored. Moreover, liver overgrowth can be induced by a variety of signals, including hepatocyte growth factor or peroxisome proliferators; the liver quickly returns to its normal size when the proliferative signal is removed. The extent to which liver stem cells mediate liver regeneration has been hotly debated. One of the primary reasons for this controversy is the use of multiple definitions for the hepatic stem cell. Definitions for the liver stem cell include the following: (1) cells responsible for normal tissue turnover, (2) cells that give rise to regeneration after partial hepatectomy, (3) cells responsible for progenitor-dependent regeneration, (4) cells that produce hepatocyte and bile duct epithelial phenotypes in vitro, and (5) transplantable liver-repopulating cells. This review will consider liver stem cells in the context of each definition. PMID:19470389

  5. Ignite Zeal for STEM Learning

    ERIC Educational Resources Information Center

    Morales, Hector

    2010-01-01

    Incorporating business skills such as problem-solving, public presentations, collaboration, and self-direction into STEM (science, technology, engineering and mathematics) subjects is an excellent way to build students' enthusiasm for these disciplines. When educators add workplace internships to the learning experience, they are well on their way…

  6. The Top STEM Degree Producers

    ERIC Educational Resources Information Center

    Diverse: Issues in Higher Education, 2012

    2012-01-01

    This article presents a list of the top Science, Technology, Engineering, and Mathematics (STEM) degree producers in the U.S. This list is broken down into seven categories: (1) Total Minority Research/Scholarship and Other Doctoral: Mathematics and Statistics; (2) Total Minority Bachelors: Biological and Biomedical Sciences; (3) Total Minority…

  7. STEM Education: Proceed with Caution

    ERIC Educational Resources Information Center

    Williams, P. John

    2011-01-01

    The STEM (science, technology, engineering and mathematics) movement has developed from a non-educational rationale. Although some think it may enliven the delivery of maths and science in classrooms, the social and economic rationales are those that have initiated this movement. Spurred on by the global financial crisis, it is hoped that…

  8. Going beyond Fun in STEM

    ERIC Educational Resources Information Center

    Pittinsky, Todd L.; Diamante, Nicole

    2015-01-01

    The United States education system must improve its ability to produce scientists, engineers, and programmers. Despite numerous national, state, and local efforts to make the study of STEM (science, technology, engineering, and mathematics) subjects more fun in K-12, initial interest in those subjects drops off precipitously in middle and later…

  9. Pancreatic stem cells remain unresolved.

    PubMed

    Jiang, Fang-Xu; Morahan, Grant

    2014-12-01

    Diabetes mellitus is caused by absolute (type 1) or relative (type 2) deficiency of insulin-secreting islet β cells. An ideal treatment of diabetes would, therefore, be to replace the lost or deficient β cells, by transplantation of donated islets or differentiated endocrine cells or by regeneration of endogenous islet cells. Due to their ability of unlimited proliferation and differentiation into all functional lineages in our body, including β cells, embryonic stem cells and induced pluripotent stem cells are ideally placed as cell sources for a diabetic transplantation therapy. Unfortunately, the inability to generate functional differentiated islet cells from pluripotent stem cells and the poor availability of donor islets have severely restricted the broad clinical use of the replacement therapy. Therefore, endogenous sources that can be directed to becoming insulin-secreting cells are actively sought after. In particular, any cell types in the developing or adult pancreas that may act as pancreatic stem cells (PSC) would provide an alternative renewable source for endogenous regeneration. In this review, we will summarize the latest progress and knowledge of such PSC, and discuss ways that facilitate the future development of this often controversial, but crucial research.

  10. Toward a Federal STEM Policy

    ERIC Educational Resources Information Center

    Brett, James T.

    2007-01-01

    Key New England industries including information technology, defense technology, biotechnology, environmental services, health care and university research rely upon people with skills in science, technology, engineering and math (STEM) fields. Yet, just 20 percent of New England high school students who took the SATs in 2005 indicated a desire to…

  11. Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease

    PubMed Central

    Ambade, Aditya; Satishchandran, Abhishek; Gyongyosi, Benedek; Lowe, Patrick; Szabo, Gyongyi

    2016-01-01

    AIM: To establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD). METHODS: Adult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed. Expression of F4/80, CD68 for macrophages and Ly6G, MPO, E-selectin for neutrophils was measured. Macrophage polarization was determined by IL-1β/iNOS (M1) and Arg-1/IL-10/CD163/CD206 (M2) expression. Liver steatosis and fibrosis were measured by oil-red-O and Sirius red staining respectively. HCC development was monitored by magnetic resonance imaging, confirmed by histology. Cellular proliferation was assessed by proliferating cell nuclear antigen (PCNA). RESULTS: Alcohol-DEN mice showed higher ALTs than pair fed-DEN mice throughout the alcohol feeding without weight gain. Alcohol feeding resulted in increased ALT, liver steatosis and inflammation compared to pair-fed controls. Alcohol-DEN mice had reduced steatosis and increased fibrosis indicating advanced liver disease. Molecular characterization showed highest levels of both neutrophil and macrophage markers in alcohol-DEN livers. Importantly, M2 macrophages were predominantly higher in alcohol-DEN livers. Magnetic resonance imaging revealed increased numbers of intrahepatic cysts and liver histology confirmed the presence of early HCC in alcohol-DEN mice compared to all other groups. This correlated with increased serum alpha-fetoprotein, a marker of HCC, in alcohol-DEN mice. PCNA immunostaining revealed significantly increased hepatocyte proliferation in livers from alcohol-DEN compared to pair fed-DEN or alcohol-fed mice. CONCLUSION: We describe a new 12-wk HCC model in adult mice that develops in livers with alcoholic hepatitis and defines ALD as co-factor in HCC. PMID:27122661

  12. Extinction models for cancer stem cell therapy

    PubMed Central

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  13. Stem cell applications in diabetes.

    PubMed

    Noguchi, Hirofumi

    2012-01-01

    Diabetes mellitus is a devastating disease and the World Health Organization (WHO) expects that the number of diabetic patients will increase to 300 million by the year 2025. Patients with diabetes experience decreased insulin secretion that is linked to a significant reduction in the number of islet cells. Type 1 diabetes is characterized by the selective destruction of pancreatic β cells caused by an autoimmune attack. Type 2 diabetes is a more complex pathology that, in addition to β cell loss caused by apoptotic programs, includes β cell de-differentiation and peripheric insulin resistance. The success achieved over the last few years with islet transplantation suggests that diabetes can be cured by the replenishment of deficient β cells. These observations are proof of the concept and have intensified interest in treating diabetes or other diseases not only by cell transplantation but also by stem cells. An increasing body of evidence indicates that, in addition to embryonic stem cells, several potential adult stem/progenitor cells derived from the pancreas, liver, spleen, and bone marrow could differentiate into insulin-producing cells in vitro or in vivo. However, significant controversy currently exists in this field. Pharmacological approaches aimed at stimulating the in vivo/ex vivo regeneration of β cells have been proposed as a way of augmenting islet cell mass. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. A new technology, known as protein transduction, facilitates the differentiation of stem cells into insulin-producing cells. Recent progress in the search for new sources of β cells has opened up several possibilities for the development of new treatments for diabetes.

  14. Embryonic Stem Cell Patents and Human Dignity

    PubMed Central

    Resnik, David B.

    2009-01-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. PMID:17922198

  15. Stem cell maintenance in a different niche

    PubMed Central

    Ahn, Ji Yeon; Lee, Seung Tae

    2013-01-01

    To overcome the difficulty of controlling stem cell fate and function in applications to regenerative medicine, a number of alternative approaches have been made. Recent reports demonstrate that a non-cellular niche modulating the biophysical microenvironment with chemical factors can support stem cell self-renewal. In our previous studies, early establishment was executed to optimize biophysical factors and it was subsequently found that the microgeometry of the extracellular matrix made huge differences in stem cell behavior and phenotype. We review here a three-dimensional, non-cellular niche designed to support stem cell self-renewal. The characteristics of stem cells under the designed system are further discussed. PMID:23875159

  16. Perspectives on human stem cell research.

    PubMed

    Jung, Kyu Won

    2009-09-01

    Human stem cell research draws not only scientists' but the public's attention. Human stem cell research is considered to be able to identify the mechanism of human development and change the paradigm of medical practices. However, there are heated ethical and legal debates about human stem cell research. The core issue is that of human dignity and human life. Some prefer human adult stem cell research or iPS cell research, others hES cell research. We do not need to exclude any type of stem cell research because each has its own merits and issues, and they can facilitate the scientific revolution when working together.

  17. Stem Cells in Teeth and Craniofacial Bones

    PubMed Central

    Zhao, H.; Chai, Y.

    2015-01-01

    Stem cells are remarkable, and stem cell–based tissue engineering is an emerging field of biomedical science aiming to restore damaged tissue or organs. In dentistry and reconstructive facial surgery, it is of great interest to restore lost teeth or craniofacial bone defects using stem cell–mediated therapy. In the craniofacial region, various stem cell populations have been identified with regeneration potential. In this review, we provide an overview of the current knowledge concerning the various types of tooth- and craniofacial bone–related stem cells and discuss their in vivo identities and regulating mechanisms. PMID:26350960

  18. Introduction to stem cells and regenerative medicine.

    PubMed

    Kolios, George; Moodley, Yuben

    2013-01-01

    Stem cells are a population of undifferentiated cells characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent). There are several sources of stem cells with varying potencies. Pluripotent cells are embryonic stem cells derived from the inner cell mass of the embryo and induced pluripotent cells are formed following reprogramming of somatic cells. Pluripotent cells can differentiate into tissue from all 3 germ layers (endoderm, mesoderm, and ectoderm). Multipotent stem cells may differentiate into tissue derived from a single germ layer such as mesenchymal stem cells which form adipose tissue, bone, and cartilage. Tissue-resident stem cells are oligopotent since they can form terminally differentiated cells of a specific tissue. Stem cells can be used in cellular therapy to replace damaged cells or to regenerate organs. In addition, stem cells have expanded our understanding of development as well as the pathogenesis of disease. Disease-specific cell lines can also be propagated and used in drug development. Despite the significant advances in stem cell biology, issues such as ethical controversies with embryonic stem cells, tumor formation, and rejection limit their utility. However, many of these limitations are being bypassed and this could lead to major advances in the management of disease. This review is an introduction to the world of stem cells and discusses their definition, origin, and classification, as well as applications of these cells in regenerative medicine.

  19. Methods for Stem Cell Production and Therapy

    NASA Technical Reports Server (NTRS)

    Claudio, Pier Paolo (Inventor); Valluri, Jagan V. (Inventor)

    2015-01-01

    The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated microgravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemotherapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.

  20. Modern stem cell therapy: approach to disease.

    PubMed

    Zemljic, Mateja; Pejkovic, Bozena; Krajnc, Ivan; Kocbek, Lidija

    2015-12-01

    Various types of stem cells exist, each with their own advantages and disadvantages. Considering the current available evidence, important preclinical and clinical studies regarding the therapeutic potential of stem cells, stem cell therapy might be the important strategy for tissue repair. The development of stem cell therapy for tissue repair has primarily relied on stem cells, especially mesenchymal stem cells. Multilineage differentiation into all of the described cells are considered as important candidates for a range of diseases like neurological diseases, cardiovascular diseases, gastrointestinal cancer and genetic defects, as well as for acute and chronic wounds healing and pharmaceutical treatment. We review the properties and multipotency of stem cells and their differentiation potential, once cultured under specific growth conditions, for use in cell-based therapies and functional tissue replacement.