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Sample records for alpha-fetoprotein afp stem

  1. AFP (alpha fetoprotein): who are you in gastrology?

    PubMed

    Sun, Wenhui; Liu, Yong; Shou, Dawei; Sun, Qiming; Shi, Jianguang; Chen, Li; Liang, Tingbo; Gong, Weihua

    2015-02-01

    AFP-producing (hepatoid differentiation) gastric cancer (GC) initially reported in 1970 plays an important role in the field of gastrology, which should be distinguished from other solid-type GCs owing to their different biological behavior. This review article aims to summarize the literature related to the role of AFP in gastric cancer and to unveil the underlying mechanism by which AFP-production impacts prognosis of GC patients. The prima facie evidence demonstrated that AFP-producing GC is more aggressive and characterized by a high incidence of venous invasion, lymphatic invasion, and metachronous and synchronous liver metastasis compared with AFP-non producing GC. Furthermore, distant metastasis was frequently observed, leading to a poorer overall prognosis. The underlying molecular mechanism is still obscure and optimal regimen remains undefined well. Nevertheless, our present study advances the knowledge of AFP-producing GC in the field of gastrology. AFP-positivity should be highlighted and an a priori enhancive intervention is needed to improve prognosis in future clinical practice. Personalized medication is strongly suggested.

  2. Heterogeneity of alpha-fetoprotein(AFP) and albumin containing cells in normal and pathological permissive states for AFP production: AFP containing cells induced in adult rats recapitulate the appearance of AFP containing hepatocytes in fetal rats.

    PubMed

    Sell, S

    1980-01-01

    The cellular localization of alpha-fetoprotein (AFP) and albumin (ALB) in permissive states for AFP synthesis has been examined. The cells containing AFP associated with permissive states in the adult are similar in appearance to cells that are present during the development of fetal liver. In fetal liver, AFP is seen in most developing hepatocytes ranging from small 'oval' like cells to larger dividing hepatocytes and in cells organized in glandular structures. Following exposure to some chemical hepatocarcinogens, AFP can also be seen in small 'oval' cells, ductal-like cells, and larger atypical hepatocytes that form glandular-like structures. Following partial hepatectomy or galactosamine-induced live injury, AFP is seen in a few large parenchymal cells usually containing identifiable chromatin Cells which contain AFP almost always contain ALB as well, but for each cell type there are many more ALB containing cells than AFP containing cells. ALB and AFP containing hepatoma cells are more frequently located adjacent to tumor vessels and AFP production by hepatoma 777 in vitro is associated with the growth state of the tumor. The AFP containing cells that are seen during restitutive proliferation most likely arise from deregulation of proliferating adult hepatocytes. The non-hepatoma AFP containing cells that appear early during carcinogenesis may arise in the adult by retrodifferentiation of hepatocytes or by proliferation of stem cells. These morphologically different AFP containing cells may or may not be precursors of the hepatocellular carcinomas which develop later.

  3. Hereditary Persistence of Alpha-Fetoprotein Is Associated with the −119G>A Polymorphism in AFP Gene

    PubMed Central

    Deshpande, Neha; Chavan, Radhika; Bale, Govardhan; Avanthi, Urmila Steffie; Aslam, Mohsin; Ramchandani, Mohan; Reddy, D. Nageshwar

    2017-01-01

    Alpha-fetoprotein (AFP) is a glycoprotein that is produced by the liver and yolk sac during fetal development. Its levels are usually raised in malignant conditions. Hereditary persistence of AFP (HPAFP) is a rare benign condition with elevated levels of AFP. It is inherited in a dominant mode with complete penetrance and is usually not associated with any clinical disability. We report two individuals with elevated levels of AFP harboring the −119G>A polymorphism in the AFP gene. A genetic screening to rule out variants in the AFP gene is advised in cases with unexplained persistent AFP levels to avoid inappropriate treatment and surgical options. PMID:28286798

  4. Hereditary Persistence of Alpha-Fetoprotein Is Associated with the -119G>A Polymorphism in AFP Gene.

    PubMed

    Deshpande, Neha; Chavan, Radhika; Bale, Govardhan; Avanthi, Urmila Steffie; Aslam, Mohsin; Ramchandani, Mohan; Reddy, D Nageshwar; Ravikanth, V V

    2017-01-01

    Alpha-fetoprotein (AFP) is a glycoprotein that is produced by the liver and yolk sac during fetal development. Its levels are usually raised in malignant conditions. Hereditary persistence of AFP (HPAFP) is a rare benign condition with elevated levels of AFP. It is inherited in a dominant mode with complete penetrance and is usually not associated with any clinical disability. We report two individuals with elevated levels of AFP harboring the -119G>A polymorphism in the AFP gene. A genetic screening to rule out variants in the AFP gene is advised in cases with unexplained persistent AFP levels to avoid inappropriate treatment and surgical options.

  5. The alpha-fetoprotein (AFP) third domain: a search for AFP interaction sites of cell cycle proteins.

    PubMed

    Mizejewski, G J

    2016-09-01

    The carboxy-terminal third domain of alpha-fetoprotein (AFP-3D) is known to harbor binding and/or interaction sites for hydrophobic ligands, receptors, and binding proteins. Such reports have established that AFP-3D consists of amino acid (AA) sequence stretches on the AFP polypeptide that engages in protein-to-protein interactions with various ligands and receptors. Using a computer software program specifically designed for such interactions, the present report identified AA sequence fragments on AFP-3D that could potentially interact with a variety of cell cycle proteins. The cell cycle proteins identified were (1) cyclins, (2) cyclin-dependent kinases, (3) cell cycle-associated proteins (inhibitors, checkpoints, initiators), and (4) ubiquitin ligases. Following detection of the AFP-3D to cell cycle protein interaction sites, the computer-derived AFP localization AA sequences were compared and aligned with previously reported hydrophobic ligand and receptor interaction sites on AFP-3D. A literature survey of the association of cell cycle proteins with AFP showed both positive relationships and correlations. Previous reports of experimental AFP-derived peptides effects on various cell cycle proteins served to confirm and verify the present computer cell cycle protein identifications. Cell cycle protein interactions with AFP-CD peptides have been reported in cultured MCF-7 breast cancer cells subjected to mRNA microarray analysis. After 7 days in culture with MCF-7 cells, the AFP-derived peptides were shown to downregulate cyclin E, SKP2, checkpoint suppressors, cyclin-dependent kinases, and ubiquitin ligases that modulate cyclin E/CdK2 transition from the G1 to the S-phase of the cell cycle. Thus, the experimental data on AFP-CD interaction with cell cycle proteins were consistent with the "in silico" findings.

  6. Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels.

    PubMed

    Xu, Wan-Ju; Guo, Bao-Li; Han, Yu-Gang; Shi, Lei; Ma, Wan-Shan

    2014-12-01

    This study aimed to investigate the clinical values of serum alpha-fetoprotein-L3 (AFP-L3) and Golgi protein 73 (GP73) in the diagnosis of hepatocellular carcinoma (HCC) with low alpha-fetoprotein (AFP). From January 2011 to December 2013, 50 low-AFP HCC patients confirmed by the color Doppler flow imaging (CDFI) and pathological examinations were collected. Forty-five patients with chronic liver diseases were also selected, including 29 liver cirrhosis patients, 15 chronic hepatitis B patients, and one severe hepatitis patient. Furthermore, 100 health volunteers with no evidence of benign or malignant liver diseases were included. The enzyme-linked immunosorbent assay (ELISA) method was applied to the GP73 quantitative assay. Serum AFP concentrations were determined using immunoassays utilizing enhanced chemiluminescence. Diagnostic accuracy of GP73 and AFP-L3 assays for low-AFP HCC was evaluated using receiver operating characteristic (ROC) curve analysis. Statistical analyses were conducted with the GraphPad Prism 5.0 software. Low-AFP HCC patients (35/50) exhibited higher positive rates of AFP-L3 than non-HCC patients (5/45) and healthy controls (2/100) (both P < 0.05). There were also significant differences in the positive rate of GP73 of low-AFP HCC patients (40/50) compared to those of non-HCC patients (3/45) and healthy controls (1/100) (both P < 0.05). However, no obvious differences in the positive rates of AFP-L3 and GP73 were observed between non-HCC patients and healthy controls (both P > 0.05). ROC curves showed that the area under the curve (AUC) of AFP-L3 for the diagnosis of low-AFP HCC was 0.6994 (sensitivity [Sen] = 70.0 %, specificity [Spe] = 95.2 %, accuracy = 88.7 %), while the AUC of GP73 was 0.8411 (Sen = 80.0 %, Spe = 97.2 %, accuracy = 92.8 %). Compared with single detection, the combination of AFP-L3 and GP73 levels for the diagnosis of low-AFP HCC showed higher Sen (94.0 %), Spe (93.1 %), and

  7. 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

  8. 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.

  9. Alpha fetoprotein

    MedlinePlus

    ... Alpha fetoprotein - series References Cunningham FG, Leveno KJ, Bloom SL, et al. Prenatal diagnosis and fetal therapy. In: Cunningham FG, Leveno KJ, Bloom SL, et al, eds. Williams Obstetrics . 23rd ed. ...

  10. Alpha fetoprotein is more than a hepatocellular cancer biomarker: from spontaneous immune response in cancer patients to the development of an AFP-based cancer vaccine.

    PubMed

    Bei, R; Mizejewski, G J

    2011-10-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with a poor prognosis and limited therapeutic options. Due to its overexpression in the majority of HCCs, alpha-fetoprotein (AFP) represents one of the most useful markers for hepatocarcinomas and for monitoring patients' response to therapy. Although it was earlier reported that AFP has immunosuppressive properties, it has been recently demonstrated that AFP induces spontaneous T and B cells responses in HCC patients. The characterization of AFP-immunogenic epitopes gives the opportunity to design AFP-based cancer vaccines for human HCC. The activity of AFP-based vaccines has been investigated in HCC mouse models in order to develop novel strategies to treat patients with HCC. This review will discuss the rationale for using the AFP-based vaccination strategy and recent results corroborating the usefulness of AFP vaccines as a potential tool for cancer therapy.

  11. Maternal serum alpha-fetoprotein levels are normal in Fanconi anemia: Can it be a lack of postnatal inhibition of AFP gene resulting in the elevation?

    PubMed

    Aslan, Deniz; Karabacak, Recep Onur; Aslan, Oner Deniz

    2017-04-01

    We investigated the feasibility of using serum alpha-fetoprotein (AFP) levels as a screening test for prenatal diagnosis of Fanconi anemia (FA). Serial measurements in maternal serum were recorded. Parents, both heterozygous for FA, had declined prenatal molecular testing. The infant was born with no somatic abnormalities, and FA was confirmed by postnatal molecular analysis. Maternal serum AFP levels during each trimester of pregnancy were normal indicating that these levels cannot be used as a screening test in prenatal diagnosis. Three-year follow-up after birth showed constantly elevated serum levels in the patient from the start, suggesting a lack of postnatal inhibition on AFP gene.

  12. Review of the Third Domain Receptor Binding Fragment of Alpha-fetoprotein (AFP): Plausible Binding of AFP to Lysophospholipid Receptor Targets.

    PubMed

    Mizejewski, G J

    2016-01-31

    Alpha-fetoprotein (AFP) is a 69 kD fetal- and tumor-associated single-chain glycoprotein belonging to the albuminoid gene family. AFP functions as a carrier/transport molecule as well as a growth regulator and has been utilized as a clinical biomarker for both fetal defects and cancer growth. Lysophospholipids (LPLs) are plasma membrane-derived bioactive lipid signaling mediators composed of a small molecular weight single acyl carbon chain (palmitic, oleic acid) attached to a polar headgroup; they range in molecular mass from 250-750 daltons. The LPLs consist of either sphingosine-1-phosphate or lysophosphatidic acid, and mostly their choline, ethanolamine, serine or inositol derivatives. They are present only in vertebrates. These bioactive paracrine lipid mediators are ubiquitously distributed in tissues and are released from many different cell types (platelets, macrophages, monocytes, etc.) involved in developmental, physiological, and pathological processes. The LPLs bind to four different classes of G-protein coupled receptors described herein which transduce a multiple of cell effects encompassing activities such as morphogenesis, neural development, angiogenesis, and carcinogenesis. The identification of potential binding sites of LPL receptors on the AFP third domain receptor binding fragment were derived by computer modeling analysis. It is conceivable, but not proven, that AFP might bind not only to the LPL receptors, but also to LPLs themselves since AFP binds medium and long chain fatty acids. It is proposed that some of the activities ascribed to AFP in the past might be due in part to the presence of bound LPLs and/or their receptors.

  13. Incorporation of alpha-fetoprotein(AFP) into subclassification of BCLC C stage hepatocellular carcinoma according to a 5-year survival analysis based on the SEER database

    PubMed Central

    Yin, Li; Wu, Jing; Du, Ming-yu; Ding, Kai; Huang, Teng; He, Xia

    2016-01-01

    Purpose To evaluate the effect of serum alpha-fetoprotein(AFP) on prognosis of patients with hepatocellular carcinoma (HCC) and put forward a proposal to modify BCLC staging system and the recommended treatment of patients with stage C. Results AFP positive was an independent poor prognostic factor of HCC. Race, pathological grade, T stage, M stage were also regarded to be significant predicted factors for poorer prognosis. When combining AFP status with AJCC stage, patients with A1 disease had a worse prognosis compared with those with A0 disease within each stage. Patients with A1 disease of each T/N stage had a worse prognosis than patients with A0 disease of the respective stage, and the prognosis of patients with A1 disease with lower T stages was worse or similar to that of patients with A0 disease of higher T stages. Materials and Methods We performed a retrospective study of all patients histologically diagnosed HCC from January 1, 2004, through December 31, 2008, from the SEER database. Conclusions AFP can be used as a subclassification index to modify the AJCC staging system of HCC. Since BCLC stage is the most widely used staging system, we recommend routine pre-treatment AFP testing as standard of care in HCC and incorporate AFP status into the BCLC staging system to modify the recommended treatment of patients with stage C. PMID:27835609

  14. Alpha-fetoprotein (AFP) modulates the effect of serum albumin on brain development by restraining the neurotrophic effect of oleic acid.

    PubMed

    García-García, Alejandro G; Polo-Hernández, Erica; Tabernero, Arantxa; Medina, José M

    2015-10-22

    We have previously shown that serum albumin controls perinatal rat brain development through the regulation of oleic acid synthesis by astrocytes. In fact, oleic acid synthesized and released by astrocytes promoted neurite growth, neuron migration and the arrangement of prospective synapses. In this work we show that alpha-fetoprotein (AFP) is also present in the brain during embryonic development, its concentrations peaking at E15.5 and at E19.5. However, after E19.5 AFP concentrations plummeted concurrently with a sharp increase in serum albumin concentrations. At E15.5, AFP is present in caudal regions of the brain, particularly in brain areas undergoing differentiation during this period, such as the thalamic reticular nucleus of the thalamus, the hypothalamus, the amygdala and the hippocampus. Albumin was not detected in the brain at E15.5 but stained brain cells substantially on day E19.5, showing a very similar distribution to that of AFP under the same circumstances. The concentrations of free oleic acid in the brain were inversely correlated with those of AFP, suggesting that the signals elicited by AFP and oleic acid can be inversely associated. GAP-43, a marker of axonal growth that is highly expressed by the presence of oleic acid, was not co-localized with AFP except in the marginal zone and areas delimiting the subplate. AFP prevented the increase in GAP-43 expression caused by the presence of oleic acid in neurons in primary culture in vitro and in organotypic cultures of embryonic rat brain ex vivo, suggesting that AFP may modulate the effect of serum albumin on brain development.

  15. Hereditary persistence of alpha-fetoprotein: a rare cause for unexplained alpha-fetoprotein elevations in pregnancy.

    PubMed

    Rood, Kara; Stiller, Robert

    2013-01-01

    Markedly elevated maternal serum alpha-fetoprotein (MSAFP) levels were found in a 26 year old healthy, nulliparous Polish woman during pregnancy. No fetal abnormalities were identified on targeted ultrasound and amniocentesis revealed normal amniotic fluid alpha-fetoprotein (AFP) values. Maternal ultrasound screening for liver and ovarian germ cell malignancies were also negative. The mother delivered a live, healthy female at term and a repeat maternal serum AFP postpartum remained markedly elevated, suggestive of hereditary persistence of alpha-fetoprotein.

  16. Alpha-fetoprotein, stem cells and cancer: how study of the production of alpha-fetoprotein during chemical hepatocarcinogenesis led to reaffirmation of the stem cell theory of cancer.

    PubMed

    Sell, Stewart

    2008-01-01

    Identification of the cells in the liver that produce alpha-fetoprotein 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. When the cellular changes in these processes were compared to 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 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, antiangiogenesis and differentiation therapy) are directed against the cancer transit-amplifying cells. When these therapies are discontinued, the cancer reforms 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 regrowth of the cancer.

  17. 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

  18. Interferometer immunosensor based on porous silicon for determining alpha-fetoprotein

    NASA Astrophysics Data System (ADS)

    Lv, Xiaoyi; Jiang, Jing; Lv, Guodong; Mo, Jiaqing; Jia, Zhenhong

    2016-10-01

    An increased level of alpha-fetoprotein ( AFP) in the blood may be a sign of liver cancer. Porous silicon based optical microcavities structure is prepared as a label-free immunosensor platform for detecting AFP. After the antigen-antibody reaction, it is monitored that the red shift of the reflection spectrum of the immunosensor increases

  19. Alpha-fetoprotein production by rhabdomyosarcoma of the urinary bladder.

    PubMed

    Badve, S S; Saxena, R; Soman, C S; Kiri, V M; Raghuvanshi, S R; Patoria, N K

    1992-12-01

    Alpha-fetoprotein has emerged as a useful diagnostic tool for hepatic tumour and tumours of germ cell origin. However, isolated case reports of association of this tumour marker with tumours of the lung and non-germ cell tumours of the ovary are reported. We present a case of a Rhabdomyosarcoma, a generally non-secretory tumour that showed raised levels of AFP in serum and reacted positively for the same in a PAP technique for AFP. Cross striations were visible in many cells on II & E stained sections.

  20. [Alpha-fetoprotein and blockade of the sexual cycle].

    PubMed

    Seralini, G E; Lafaurie, M; Castelli, D; Krebs, B; Stora, C

    1984-01-01

    During chemical hepatocarcinogenesis by N-2 fluorenylacetamide in adult female Rats, vaginal cycle alterations were observed after 30 days of carcinogenic diet, and a blocking at the metestrus stage appeared from the 70th day. This may be explained by the very low serum progesterone level prevailing after the 50th day. An important drop in ovary weight was also noticed; together with the blocking of follicular maturation and ovulation leading to a marked follicular atresia. Simultaneously, alpha-fetoprotein (AFP) seems to interact in the lowering of progesterone level, and AFP was found ten times higher in the serum of treated animals than in controls. AFP was localized in degenerative oocyte cytoplasm by immunofluorescence in the treated animals, but not in the controls. In conclusion, a blocking role of AFP on genital cycles and a relationship between AFP and follicular atresia are suggested.

  1. [Effect of alpha-fetoprotein on isolated mouse oocytes].

    PubMed

    Lambert, J C; Vallette, G; Seralini, G E; Vranckx, R; Nunez, E; Stora, C

    1986-01-01

    Data are presented which indicate a possible action of alpha-fetoprotein (AFP) on female germinal cells. The in vitro maturation of mature mice oocytes was significantly inhibited when mouse AFP replaced albumin in the culture medium. In addition, the degenerative aspect of oocytes cultured with AFP seemed to indicate that this meïotic inhibition was caused by a premature degeneration of oocytes rather than by a blockage at a specific stage of maturation. Thus AFP, perhaps through its ligands, may play a role in the reduction of germinal cells during fetal and immediate post-natal life rather than in the arrest of meïosis at the diplotene stage.

  2. Molecular mechanisms of alpha-fetoprotein gene expression.

    PubMed

    Lazarevich, N L

    2000-01-01

    Alpha-fetoprotein (AFP) is the main component of mammalian fetal serum. It is synthesized by visceral endoderm of the yolk sac and by fetal liver. Immediately after birth AFP level in blood decreases dramatically. AFP synthesis is reactivated in liver tumors and germinogeneous teratoblastomas, in a lesser degree after chemical and mechanical liver injuries followed by regeneration (i.e., acute viral hepatitis). AFP blood level change is an important marker for liver tumors that is widely used in clinical practice. Therefore, the study of the molecular and cellular mechanisms participating in regulation of the oncoembryonal protein AFP is an important task. On various experimental models it has been shown that the expression is regulated mainly on the transcriptional level, the AFP gene having a 7 kb regulatory region upstream. Within this region a tissue-specific promoter, three independent enhancers, and a silencer that is at least partially responsible for AFP gene expression decrease in adult liver have been defined. Some ubiquitous and some tissue-specific transcription factors, including hepatocyte nuclear factors (HNFs), which mediate the transcription of most of the liver-specific genes, have been shown to bind to the promoter. However, the mechanisms determining drastic changes of AFP synthesis level in the course of ontogenesis and carcinogenesis remain incompletely clarified. Also, little is known about negative regulators of AFP gene expression in cells of non-hepatic origin and in adult liver.

  3. 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.

  4. 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

  5. Clinicopathological characteristics and prognosis of alpha-fetoprotein positive gastric cancer in Chinese patients

    PubMed Central

    Wang, Daguang; Li, Chunping; Xu, Yuechao; Xing, Yanpeng; Qu, Limei; Guo, Yuchen; Zhang, Yang; Sun, Xuan; Suo, Jian

    2015-01-01

    Purpose: This study aimed to review the clinicopathological, histochemical, and prognostic features of Alpha-Fetoprotein (AFP) positive gastric cancer. Patients and methods: Six hundred and fifty one patients with gastric cancer who underwent gastrectomy between January 2009 and December 2012 at The First Hospital of Jilin University were enrolled in the study. Among them, 45 patients were identified as AFP positive gastric cancer. The clinicopathologic characteristics and prognosis of the AFP positive gastric cancer patients were analyzed. Results: Among the 45 AFP positive patients, serum levels of AFP were < 100 µg/L in nine patients. The histological classification of 45 patients was as follows: hepatoid type, 25 (55.6%) cases; fetal gastrointestinal type, 12 (26.7%) cases; yolk sac tumor type, 2 (4.4%) cases; and mixed type, 6 (13.3%) cases. Twenty nine (64.4%) cases were AFP positive by immunohistochemical analysis; we found no significant difference in AFP positivity and histologic type. However, the differences in the number of metastasis lymph nodes, the maximum tumor diameter, pathological stage, vascular invasion and liver metastasis between the AFP positive group and the negative group were significant. At the same T stage, the liver metastasis status of the AFP positive group was higher than that of the negative group. The AFP positive group had a much poorer prognosis than the negative group. Conclusion: AFP positive gastric cancer is associated with aggressive behavior and poorer prognosis compared to that of AFP negative gastric cancer. PMID:26261510

  6. T cell responses to HLA-A*0201-restricted peptides derived from human alpha fetoprotein.

    PubMed

    Butterfield, L H; Meng, W S; Koh, A; Vollmer, C M; Ribas, A; Dissette, V B; Faull, K; Glaspy, J A; McBride, W H; Economou, J S

    2001-04-15

    alpha fetoprotein (AFP)-derived peptide epitopes can be recognized by human T cells in the context of MHC class I. We determined the identity of AFP-derived peptides, presented in the context of HLA-A*0201, that could be recognized by the human (h) T cell repertoire. We screened 74 peptides and identified 3 new AFP epitopes, hAFP(137-145), hAFP(158-166), and hAFP(325-334), in addition to the previously reported hAFP(542-550.) Each possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent class I binding assay. The peptides were stable for 2-4 h in an off-kinetics assay. Each peptide induced peptide-specific T cells in vitro from several normal HLA-A*0201 donors. Importantly, these hAFP peptide-specific T cells also were capable of recognizing HLA-A*0201(+)/AFP(+) tumor cells in both cytotoxicity assays and IFN-gamma enzyme-linked immunospot assays. The immunogenicity of each peptide was tested in vivo with HLA-A*0201/K(b)-transgenic mice. After immunization with each peptide emulsified in CFA, draining lymph node cells produced IFN-gamma on recognition of cells stably transfected with hAFP. Furthermore, AFP peptide-specific T cells could be identified in the spleens of mice immunized with dendritic cells transduced with an AFP-expressing adenovirus (AdVhAFP). Three of four AFP peptides could be identified by mass spectrometric analysis of surface peptides from an HLA-A*0201 human hepatocellular carcinoma (HCC) cell line. Thus, compelling immunological and physiochemical evidence is presented that at least four hAFP-derived epitopes are naturally processed and presented in the context of class I, are immunogenic, and represent potential targets for hepatocellular carcinoma immunotherapy.

  7. Alpha-fetoprotein activates AKT/mTOR signaling to promote CXCR4 expression and migration of hepatoma cells.

    PubMed

    Zhu, Mingyue; Guo, Junli; Xia, Hua; Li, Wei; Lu, Yan; Dong, Xu; Chen, Yi; Xie, Xieju; Fu, Shigan; Li, Mengsen

    2015-01-01

    CXCR4, stromal cell-derived factor-1α(SDF 1α) receptor, stimulates growth and metastasis of hepatocellular carcinoma (HCC). Alpha-fetoprotein(AFP) governs the expression of some metastasis-related genes. Here we report that AFP and CXCR4 levels correlated in HCC tissues. AFP-expressing vectors induced CXCR4. In agreement, AFP depletion by siRNA decreased CXCR4. AFP co-localized and interacted with PTEN, thus inducing CXCR4 by activating AKT(Ser473) phosphorylation. In turn, phospho-mTOR(Ser2448) entered the nucleus and bound the CXCR4 gene promoter. Thus, AFP promoted migration of HCC cells. In concusion, AFP induced CXCR4 by activating the AKT/mTOR signal pathway.

  8. Alpha-fetoprotein activates AKT/mTOR signaling to promote CXCR4 expression and migration of hepatoma cells

    PubMed Central

    Li, Wei; Lu, Yan; Dong, Xu; Chen, Yi; Xie, Xieju; Fu, Shigan; Li, Mengsen

    2015-01-01

    CXCR4, stromal cell-derived factor-1α(SDF 1α) receptor, stimulates growth and metastasis of hepatocellular carcinoma (HCC). Alpha-fetoprotein(AFP) governs the expression of some metastasis-related genes. Here we report that AFP and CXCR4 levels correlated in HCC tissues. AFP-expressing vectors induced CXCR4. In agreement, AFP depletion by siRNA decreased CXCR4. AFP co-localized and interacted with PTEN, thus inducing CXCR4 by activating AKT(Ser473) phosphorylation. In turn, phospho-mTOR(Ser2448) entered the nucleus and bound the CXCR4 gene promoter. Thus, AFP promoted migration of HCC cells. In concusion, AFP induced CXCR4 by activating the AKT/mTOR signal pathway. PMID:25815363

  9. 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.

  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. An electrochemical biosensor for the assay of alpha-fetoprotein-L3 with practical applications.

    PubMed

    Li, Jinlong; Gao, Tao; Gu, Shiyu; Zhi, Jun; Yang, Jie; Li, Genxi

    2017-01-15

    The detection of alpha-fetoprotein-L3 (AFP-L3) is of great importance for hepatocellular carcinoma (HCC) diagnosis, but remains unsatisfactory owing to poor sensitivity and complex operating steps. In this work, a simple and sensitive method has been proposed for the detection of AFP-L3. Firstly, biotinylated Lens culinaris agglutinin-integrated silver nanoparticles (B-LCA-AgNPs) is fabricated. Owing to the specific interaction between Lens culinaris agglutinin and AFP-L3, AFP-L3 can be detected directly through the electrochemical signal readout of AgNPs, avoiding separated steps used in clinical practice. Furthermore, after the recognition between B-LCA-AgNPs and AFP-L3, large amount of AgNPs can be gathered at the binding site through avidin-biotin interactions, which can amplify the signal. Therefore, detection of AFP-L3 can be sensitively achieved. Moreover, compared with the other approaches, this new method has a better linear correlation (25-15,000pg/mL) and a lower detection limit (12pg/mL). Also, the new method developed in this work has been demonstrated to have good stability and reproducibility for the assay of AFP-L3 in human serum samples, so, it may hold a great application prospect in clinical diagnostics.

  12. 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. PMID:27703963

  13. Nanobody medicated immunoassay for ultrasensitive detection of cancer biomarker alpha-fetoprotein.

    PubMed

    Chen, Jing; He, Qing-hua; Xu, Yang; Fu, Jin-heng; Li, Yan-ping; Tu, Zhui; Wang, Dan; Shu, Mei; Qiu, Yu-lou; Yang, Hong-wei; Liu, Yuan-yuan

    2016-01-15

    Immunoassay for cancer biomarkers plays an important role in cancer prevention and early diagnosis. To the development of immunoassay, the quality and stability of applied antibody is one of the key points to obtain reliability and high sensitivity for immunoassay. The main purpose of this study was to develop a novel immunoassay for ultrasensitive detection of cancer biomarker alpha-fetoprotein (AFP) based on nanobody against AFP. Two nanobodies which bind to AFP were selected from a phage display nanobody library by biopanning strategy. The prepared nanobodies are clonable, thermally stable and applied in both sandwich enzyme linked immunoassay (ELISA) and immuno-PCR assay for ultrasensitive detection of AFP. The limit detection of sandwich ELISA setup with optimized nanobodies was 0.48ng mL(-1), and the half of saturation concentration (SC50) value was 6.68±0.56ng mL(-1). These nanobodies were also used to develop an immuno-PCR assay for ultrasensitive detection of AFP, its limit detection values was 0.005ng mL(-1), and the linear range was 0.01-10,000ng mL(-1). These established immunoassays based on nanobodies were highly specific to AFP and with negligible cross reactivity with other tested caner biomarkers. Furthermore, this novel concept of nanobodies mediated immunoassay may provide potential applications in a general method for the ultrasensitive detection of various cancer biomarkers.

  14. Alpha fetoprotein antagonises benzyl isothiocyanate inhibition of the malignant behaviors of hepatocellular carcinoma cells

    PubMed Central

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

    2016-01-01

    Benzyl isothiocyanate (BITC) is a dietary isothiocyanate derived from cruciferous vegetables. Recent studies showed that BITC inhibited the growth of many cancer cells, including hepatocellular carcinoma (HCC) cells. Alpha-fetoprotein (AFP) is a important molecule for promoting progression of HCC, in the present investigation, we explore the influence of AFP on the role of BITC in the malignant behaviours of HCC cells, and the potential underlying mechanisms. We found thatBITC inhibited viability, migration, invasion and induced apoptosis of human liver cancer cell lines, Bel 7402(AFP producer) and HLE(non-AFP producer) cells in vitro. The role of BITC involve in promoting actived-caspase-3 and PARP-1 expression, and enhancing caspase-3 activity but decreasing MMP-2/9, survivin and CXCR4 expression. AFP antagonized the effect of BITC. This study suggests that BITC induced significant reductions in the viability of HCC cell lines. BITC may activate caspase-3 signal and inhibit the expression of growth- and metastasis-related proteins; AFP is an pivotal molecule for the HCC chemo-resistance of BITC. PMID:27716619

  15. [Alpha fetoprotein in umbilical cord blood].

    PubMed

    Guibaud, S; Bonnet, M; Thoulon, J M; Dorche, J; Dumont, M

    1975-02-08

    Quantitative measurement of alpha-foetoprotein was made on the cord blood of 158 new-born of gestational age ranging between 15 and 43 weeks. The technique used was that of simple radial immunodiffusion of Mancini which made possible the exact measurement of A.F.P. in all the specimens apart from 3. The correlation coefficient between the A.F.P. level in cord blood and gestational age is significant (r equals 0,85 for a risk p equals 0,001). However, the degree of difference at a given point in pregnancy and the difference in levels found in certain cases of twin pregnancies, suggest that factors other than gestational age (certain complications of pregnancy, for example) may influence foetal A,F.P.

  16. Optimizing Surveillance Performance of Alpha-Fetoprotein by Selection of Proper Target Population in Chronic Hepatitis B

    PubMed Central

    Chung, Jung Wha; Kim, Beom Hee; Lee, Chung Seop; Kim, Gi Hyun; Sohn, Hyung Rae; Min, Bo Young; Song, Joon Chang; Park, Hyun Kyung; Jang, Eun Sun; Yoon, Hyuk; Kim, Jaihwan; Shin, Cheol Min; Park, Young Soo; Hwang, Jin-Hyeok; Jeong, Sook-Hyang; Kim, Nayoung; Lee, Dong Ho; Lee, Jaebong; Ahn, Soyeon

    2016-01-01

    Although alpha-fetoprotein (AFP) is the most widely used biomarker in hepatocellular carcinoma (HCC) surveillance, disease activity may also increase AFP levels in chronic hepatitis B (CHB). Since nucleos(t)ide analog (NA) therapy may reduce not only HBV viral loads and transaminase levels but also the falsely elevated AFP levels in CHB, we tried to determine whether exposure to NA therapy influences AFP performance and whether selective application can optimize the performance of AFP testing in CHB during HCC surveillance. A retrospective cohort of 6,453 CHB patients who received HCC surveillance was constructed from the electronic clinical data warehouse. Covariates of AFP elevation were determined from 53,137 AFP measurements, and covariate-specific receiver operating characteristics regression analysis revealed that albumin levels and exposure to NA therapy were independent determinants of AFP performance. C statistics were largest in patients with albumin levels ≥ 3.7 g/dL who were followed without NA therapy during study period, whereas AFP performance was poorest when tested in patients with NA therapy during study and albumin levels were < 3.7 g/dL (difference in C statics = 0.35, p < 0.0001). Contrary to expectation, CHB patients with current or recent exposure to NA therapy showed poorer performance of AFP during HCC surveillance. Combination of concomitant albumin levels and status of NA therapy can identify subgroup of CHB patients who will show optimized AFP performance. PMID:27997559

  17. Transient expression of a mouse alpha-fetoprotein minigene: deletion analyses of promoter function.

    PubMed Central

    Scott, R W; Tilghman, S M

    1983-01-01

    The constitutive transcription of a mouse alpha-fetoprotein (AFP) minigene was examined during the transient expression of AFP-simian virus 40-pBR322 recombinant DNAs introduced into HeLa cells by Ca3(PO4)2 precipitation. We tested three constructs, each of which contains the AFP minigene and pBR322 DNAs inserted in the late region of simian virus 40 and found that the relative efficiency of AFP gene expression was dependent on the arrangement of the three DNA elements in the vector. The transcripts begin at the authentic AFP cap site and are properly spliced and polyadenylated. To define a sequence domain in the 5' flanking region of the AFP gene required for constitutive expression, sequential 5' deletion mutants of the AFP minigene were constructed and introduced into HeLa cells. All AFP deletion mutants which retained at least the TATA motif located 30 base pairs upstream from the cap site were capable of directing accurate and efficient AFP transcription. However, when the TATA sequence was deleted, no accurately initiated AFP transcripts were detected. These results are identical to those obtained from in vitro transcription of truncated AFP 5' deletion mutant templates assayed in HeLa cell extracts. The rate of AFP transcription in vivo was unaffected by deletion of DNA upstream of the AFP TATA box but was greatly affected by the distance between the simian virus 40 control region and the 5' end of the gene. The absence of any promoter activity upstream of the TATA box in this assay system is in contrast to what has been reported for several other eucaryotic structural genes in a variety of in vivo systems. A sequence comparison between the 5' flanking region of the AFP gene and these genes suggested that the AFP gene lacks those structural elements found to be important for constitutive transcription in vivo. Either the AFP gene lacks upstream promoter function in the 5' flanking DNA contained within the minigene, or the use of a viral vector in a

  18. Inducible protein in rat hepatomas with expression alternative to alpha-fetoprotein.

    PubMed

    Eraiser, T L; Yazova, A K; Poltoranina, V S; Kuprina, N I; Karamova, E R; Shipova, L Y; Lazarevich, N L; Abelev, G I

    1998-01-30

    The rat hepatoma cell line McA RH7777 was cloned into alpha-fetoprotein-producing (AFP+) and non-producing (AFP-) sublines. A monoclonal antibody (MAb A2/3) reacting with an antigen (Ag A2/3) present only in AFP- clones or AFP- cells in mixed clones was obtained. Ag A2/3 was absent from the liver of embryonic, fetal, newborn and adult rats, but it was present in gastric and intestinal mucosa of adult rats. Ag A2/3 was found to be a heavy metal-inducible protein: Cd2+ and Pb2+ strongly induced the expression of Ag A2/3 in vivo in the liver of adult rats, while xenobiotics and CCl4 were not active in this respect. In vitro Cd2+ and Pb2+ induced Ag A2/3 expression in several AFP+ clones, leading to a simultaneous marked decrease of AFP+ cells from such clones. The effect of Cd2+ in the induction of Ag A2/3 and suppression of AFP was reversible. SDS PAGE revealed one protein band with an m.w. close to 45,000, which was not sensitive to mercaptoethanol. Despite its inducible properties, Ag A2/3 was shown not to belong to metallothioneins, cytochrome P-450, glutathion-transferase or heat shock proteins families, well-known as being inducible cell stress proteins. Expression of Ag A2/3 could be one of the factors determining the high amplitude of AFP production by individual liver tumors. The nature of Ag A2/3 and its alternative expression with respect to AFP remain to be studied.

  19. Tumor-derived alpha-fetoprotein impairs the differentiation and T cell stimulatory activity of human dendritic cells

    PubMed Central

    Pardee, Angela D.; Shi, Jian; Butterfield, Lisa H.

    2014-01-01

    Several tumor-derived factors have been implicated in DC dysfunction in cancer patients. Alpha-fetoprotein (AFP) is an oncofetal antigen that is highly expressed in abnormalities of prenatal development and several epithelial cancers, including hepatocellular carcinoma (HCC). In HCC patients exhibiting high levels of serum AFP, we have observed a lower ratio of myeloid-to-plasmacytoid circulating DC compared to patients with low serum AFP levels and healthy donors. To test the effect of AFP on DC differentiation in vitro, peripheral blood monocytes from healthy donors were cultured in the presence of cord blood-derived normal AFP (nAFP) or HCC tumor-derived AFP (tAFP), and DC phenotype and function was assessed. Although the nAFP and tAFP isoforms only differ at one carbohydrate group, low (physiological) levels of tAFP, but not nAFP, significantly inhibited DC differentiation. tAFP-conditioned DC expressed diminished levels of DC maturation markers, retained a monocyte-like morphology, exhibited limited production of inflammatory mediators, and failed to induce robust T cell proliferative responses. Mechanistic studies revealed that the suppressive activity of tAFP is dependent on the presence of low molecular weight (LMW) species that i) co-purify with tAFP, and ii) function equivalently to the LMW fractions of both tumor and non-tumor cell lysates. These data reveal the unique ability of tAFP to serve as a chaperone protein for LMW molecules, both endogenous and ubiquitous in nature, which function cooperatively to impair DC differentiation and function. Therefore, novel therapeutic approaches that antagonize the regulatory properties of tAFP will be critical to enhance immunity and improve clinical outcomes. PMID:25355916

  20. Development and validation of an alpha fetoprotein immunoassay using Gyros technology.

    PubMed

    Given, Allison M; Whalen, Pamela M; O'Brien, Peter J; Ray, Chad A

    2012-05-01

    Circulating alpha fetoprotein (AFP) is a diagnostic and prognostic biomarker for hepatocellular carcinoma (HCC) with potential utility as a pharmacodynamic endpoint in rodent tumor models. This application is limited, however, by low sample volumes, highlighting the need for sensitive, sample-sparing biomarker assay methods. In order to improve the utility of AFP as an oncology biomarker, we developed a method for AFP using the Gyrolab™, an automated microimmunoassay platform. Commercially available antibodies were screened to identify optimal combinations that were then used in a multi-factorial design of experiments (DOE) to optimize reaction conditions. Analytical validation included assessments of accuracy and precision (A&P), and dilutional linearity/hook effect, as well as reagent and sample stability. The method is reliable, with total error, a measure of accuracy and precision, less than 30% for all concentrations tested. AFP concentrations were measurable in diseased mice and undetectable in normal mice. Therefore, this novel, low volume AFP immunoassay is suitable for pre-clinical drug development, where its miniaturized format facilitates serial sampling in rodent models of cancer.

  1. 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

  2. Detection of alpha-fetoprotein in magnetic immunoassay of thin channels using biofunctional nanoparticles

    NASA Astrophysics Data System (ADS)

    Tsai, H. Y.; Gao, B. Z.; Yang, S. F.; Li, C. S.; Fuh, C. Bor

    2014-01-01

    This paper presents the use of fluorescent biofunctional nanoparticles (10-30 nm) to detect alpha-fetoprotein (AFP) in a thin-channel magnetic immunoassay. We used an AFP model biomarker and s-shaped deposition zones to test the proposed detection method. The results show that the detection using fluorescent biofunctional nanoparticle has a higher throughput than that of functional microparticle used in previous experiments on affinity reactions. The proposed method takes about 3 min (versus 150 min of previous method) to detect 100 samples. The proposed method is useful for screening biomarkers in clinical applications, and can reduce the run time for sandwich immunoassays to less than 20 min. The detection limits (0.06 pg/ml) and linear ranges (0.068 pg/ml-0.68 ng/ml) of AFP using fluorescent biofunctional nanoparticles are the same as those of using functional microparticles within experimental errors. This detection limit is substantially lower and the linear range is considerably wider than those of enzyme-linked immunosorbent assay (ELISA) and other methods in sandwich immunoassay methods. The differences between this method and an ELISA in AFP measurements of serum samples were less than 12 %. The proposed method provides simple, fast, and sensitive detection with a high throughput for biomarkers.

  3. Construction and expression in vivo of an internally deleted mouse alpha-fetoprotein gene: presence of a transcribed Alu-like repeat within the first intervening sequence.

    PubMed Central

    Young, P R; Scott, R W; Hamer, D H; Tilghman, S M

    1982-01-01

    An alpha-fetoprotein (AFP) 'minigene' was constructed by joining the first two exons along with 0.9 kilobases of 5' flanking sequence of the mouse AFP gene to its last exon and 0.4 kilobases of 3' flanking sequence. This 'minigene' was tested for activity by inserting it into an SV40 vector and infecting African green monkey kidney cells. Correct initiation, termination, polyadenylation and splicing were observed. Furthermore a 220 nucleotide transcript was detected and mapped to a mouse Alu-like or B1 repeat on the opposite strand to that encoding the AFP gene in the first intervening sequence. Images PMID:6179043

  4. 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

  5. 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.

  6. Changes in alpha-fetoprotein and albumin synthesis rates and their levels during fetal and neonatal development of rat brain.

    PubMed

    Ali, M; Sahib, M K

    1983-02-01

    An attempt was made to find a correlation between AFP and albumin levels in brain and their rates of synthesis in the brain cells during maturation of rat brain. Levels of alpha-fetoprotein (AFP) and albumin in the developing brain were studied by rocket immunoassay. Rate of synthesis of AFP and albumin in brain cell cultures, established from rat brain at various stages of development, were determined by incorporation of [14C]leucine into immuno-precipitable intracellular AFP and albumin. AFP and albumin levels in brain as well as rates of their synthesis by brain cells in culture registered a continuous decline during development. Synthesis of AFP and albumin in the brain is switched off after first week of postnatal life with a concomitant disappearance of these proteins from the brain. Levels of AFP and albumin in brain correlated well with rates of their synthesis by brain cells in vitro at any specific stage of brain maturation implying that levels of AFP and albumin in brain are regulated by controlling rates of their synthesis in the maturing brain cells.

  7. 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

  8. The alpha-fetoprotein knock-out mouse model suggests that parental behavior is sexually differentiated under the influence of prenatal estradiol.

    PubMed

    Keller, Matthieu; Pawluski, Jodi L; Brock, Olivier; Douhard, Quentin; Bakker, Julie

    2010-04-01

    In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the alpha-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of alpha-fetoprotein against maternal estradiol and as a result represents a good model to determine the contribution of prenatal estradiol to the sexual differentiation of the brain and behavior. Female AFP-KO mice were defeminized and masculinized with regard to their neuroendocrine responses as well as sexual behavior. Since parental behavior is also strongly sexually differentiated in mice, we used the AFP-KO mouse model here to ask whether parental responses are differentiated prenatally under the influence of estradiol. It was found that AFP-KO females showed longer latencies to retrieve pups to the nest and also exhibited lower levels of crouching over the pups in the nest in comparison to WT females. In fact, they resembled males (WT and AFP-KO). Other measures of maternal behavior, for example the incidence of infanticide, tended to be higher in AFP-KO females than in WT females but this increase failed to reach statistical significance. The deficits observed in parental behavior of AFP-KO females could not be explained by any changes in olfactory function, novelty recognition or anxiety. Thus our results suggest that prenatal estradiol defeminizes the parental brain in mice.

  9. A Portable Immunosensor with Differential Pressure Gauges Readout for Alpha Fetoprotein Detection.

    PubMed

    Wang, Qingping; Li, Rongjie; Shao, Kang; Lin, Yue; Yang, Weiqiang; Guo, Longhua; Qiu, Bin; Lin, Zhenyu; Chen, Guonan

    2017-03-24

    A portable, affordable and simple detector is requested in a "Point-of-Care-Testing" (POCT) system. In this study, we exploited the potentialities of Differential Pressure Gauge (DPG) to the orientation of POCT technology. Alpha fetoprotein (AFP) was chosen as a model analyte that could specifically recognized by its antigen, and a tiny outfits equipped with a DPG was employed as the signal readout. Pt/SiO2 nanospheres were synthesized and modified with the detection antibody. In the presence of target, a sandwich of immunocomplex specifically formed and the Pt/SiO2 had been modified on the capture antibody. Which then can be dissolved to release plenty of Pt and the suspensions were transferred into a closed vial filled with appropriated amount of hydrogen peroxide. Subsequently, hydrogen peroxide was decomposed to produce oxygen, resulting in the enhancement of pressure in the closed vial and which can be detected by DPG easily. Under the optimized conditions, the read out signal from DPG had a direct relationship with AFP concentrations in the range of 10~200 ng/mL, and the detection limit was as low as 3.4 ng/mL. The proposed portable sensor had been successfully applied to detect AFP in serum samples with satisfactory results. This strategy holds a great promising in biological analysis as its convenient operations, reliable results and flexible apparatus.

  10. Photonic crystal fiber-based immunosensor for high-performance detection of alpha fetoprotein.

    PubMed

    Liu, Xiaoxia; Song, Xingda; Dong, Zhiyong; Meng, Xiaoting; Chen, Yiping; Yang, Li

    2017-05-15

    We have developed a sensitive photonic crystal fiber (PCF)-based immunosensor for detection of alpha fetoprotein (AFP). The unique PCF possesses a morphology characterized by numerous pore structures and a large surface area-to-volume ratio, which can be used as an immune-reaction carrier to improve the sensitivity and reaction speed of AFP detection. The PCF-based immunosensor possesses a low limit of detection of 0.1ng/mL, which is five times lower than that of the capillary-based sensor and 35 times lower than that of the traditional enzyme-linked immunosorbent assay. The wide linear dynamic range of 0.1-150ng/mL makes the developed immunosensor suitable for clinical practice. The proposed method was successfully applied to AFP detection in a clinical serum sample with acceptable precision. It is indicated that the present PCF-based immunosensor could be used as an attractive analytical platform for sensitive and specific detection of cancer biomarkers.

  11. A Portable Immunosensor with Differential Pressure Gauges Readout for Alpha Fetoprotein Detection

    PubMed Central

    Wang, Qingping; Li, Rongjie; Shao, Kang; Lin, Yue; Yang, Weiqiang; Guo, Longhua; Qiu, Bin; Lin, Zhenyu; Chen, Guonan

    2017-01-01

    A portable, affordable and simple detector is requested in a “Point-of-Care-Testing” (POCT) system. In this study, we exploited the potentialities of Differential Pressure Gauge (DPG) to the orientation of POCT technology. Alpha fetoprotein (AFP) was chosen as a model analyte that could specifically recognized by its antigen, and a tiny outfits equipped with a DPG was employed as the signal readout. Pt/SiO2 nanospheres were synthesized and modified with the detection antibody. In the presence of target, a sandwich of immunocomplex specifically formed and the Pt/SiO2 had been modified on the capture antibody. Which then can be dissolved to release plenty of Pt and the suspensions were transferred into a closed vial filled with appropriated amount of hydrogen peroxide. Subsequently, hydrogen peroxide was decomposed to produce oxygen, resulting in the enhancement of pressure in the closed vial and which can be detected by DPG easily. Under the optimized conditions, the read out signal from DPG had a direct relationship with AFP concentrations in the range of 10~200 ng/mL, and the detection limit was as low as 3.4 ng/mL. The proposed portable sensor had been successfully applied to detect AFP in serum samples with satisfactory results. This strategy holds a great promising in biological analysis as its convenient operations, reliable results and flexible apparatus. PMID:28338068

  12. Amniotic fluid alpha-fetoprotein testing in native Japanese women.

    PubMed

    Onda, T; Fukushima, K; Tanaka, T; Sawa, R; Hayashi, Z; Tsutsumi, O; Takai, Y; Yoshida, K; Nakamura, Y; Hoshi, K; Fukada, Y; Okai, T; Sakai, M; Kitagawa, M; Akiyama, Y; Shimomura, K; Myrick, F; Dowman, A C; Grier, R E

    1999-08-01

    Owing to differences in maternal serum alpha-fetoprotein, human chorionic gonadotrophin and oestriol levels between native Japanese and Caucasian women screened in this laboratory, a study was conducted to measure amniotic fluid alpha-fetoprotein (AFAFP) levels in native Japanese pregnancies. When the native Japanese AFAFP levels were compared with a United States (non-Black) population, the Japanese medians did not decrease as rapidly over the 14 to 22 weeks of gestation period investigated. At 14 weeks, the difference was negligible, graduating to a difference of 20 per cent by 22 weeks' gestation. Native Japanese pregnancy AFAFP levels should be interpreted based upon population data from that group alone. From these findings, prenatal screening laboratories should be encouraged to collect preliminary data for comparison before screening is initiated for a defined ethnic group.

  13. [New protein vectors based on an alpha-fetoprotein fragment for targeted DNA delivery into cancer cells].

    PubMed

    Tatarinova, O N; Gorokhovets, N V; Makarov, V A; Posypanova, G A; Serebriakova, M V; Pozmogova, G E

    2010-01-01

    A human alpha-fetoprotein fragment (AFP) modified with oligocationic homologs of nuclear localization signal was used to construct new target cell-selective DNA-carrier proteins. The new recombinant vectors containing C- or N-terminal polynucleotide-binding domains are able to form stable complexes with single- or double-stranded oligonucleotides and plasmid DNA. Using flow cytometry and fluorescent microscopy, it was shown that such nucleoprotein complexes can be selectively internalized in target cells receptors superexpressing AFP receptors. The results obtained are important both for understanding mechanisms of formation of DNA-protein complexes and for studying their interaction with intracellular molecular targets. The new proteins can be used as a tool for the development of highly selective and efficacious gene-selective antitumour drugs.

  14. Chemotherapy by intravenous administration of conjugates of daunomycin with monoclonal and conventional anti-rat alpha-fetoprotein antibodies.

    PubMed Central

    Tsukada, Y; Hurwitz, E; Kashi, R; Sela, M; Hibi, N; Hara, A; Hirai, H

    1982-01-01

    Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested in vitro and in vivo for their anti-tumor activity. They were equally cytotoxic to rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates either by intraperitoneal or intravenous injections. Daunomycin conjugates with horse anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal immunoglobulin. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls delayed only slightly tumor development. PMID:6185954

  15. Biological role of alpha-fetoprotein in cancer: prospects for anticancer therapy.

    PubMed

    Mizejewski, Gerald J

    2002-12-01

    alpha-fetoprotein has long been considered the 'gold-standard' in the field of tumor markers. During the several decades since the recognition of mammalian alpha-fetoprotein as a tumor-associated fetal protein, it has been purified, characterized, cloned and sequenced for use in the clinical diagnostic laboratory. However, the biological role of alpha-fetoprotein in the regulation of cancer growth has received comparatively little attention. Only during the last decade has the modulatory role of alpha-fetoprotein in neoplastic growth been realized and implemented in experimental models. This review examines the basis for the current consensus that alpha-fetoprotein does indeed regulate neoplastic growth through the presence of an alpha-fetoprotein cell surface receptor that undergoes internalization to the cell interior. Studies involving uptake of this fetal protein have since culminated in radio imaging reports as well as the use of alpha-fetoprotein as an anticancer drug conjugate. Finally, the therapeutic utilization of alpha-fetoprotein and its peptidic fragments as growth-response modifiers encompasses biological events, such as apoptosis G-coupled signal transduction, gene therapy, vaccination and cancer chemoprevention.

  16. Development of Ligand-Transformed Alpha-Fetoprotein for Use Against Breast Cancer in Humans.

    DTIC Science & Technology

    1996-07-01

    Cancer Inst., 64: 1147-1152, 1980. 20. Brock, D. J., and Sutcliffe, R. G. Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida...G. Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet 1972: 2:197-8. 32. Janerich, D. T., Mayne, S. T., Thompson, W

  17. Measurement of Glycosylated Alpha-Fetoprotein Improves Diagnostic Power over the Native Form in Hepatocellular Carcinoma

    PubMed Central

    Jin, Jonghwa; Park, Jiyoung; Yu, Su Jong; Yoon, Jung-Hwan; Kim, Youngsoo

    2014-01-01

    Serum alpha-fetoprotein (AFP) has long been used as a diagnostic marker for hepatocellular carcinoma (HCC), albeit controversially. Although it remains widely used in clinics, the value of AFP in HCC diagnosis has recently been challenged due to its significant rates of false positive and false negative findings. To improve the efficacy of AFP as HCC diagnostic marker, we developed a method of measuring total and glycosylated AFP by multiple reaction monitoring (MRM)-MS. In this study, we verified the total amount of AFP (nonglycopeptide levels) and the degree of glycosylated AFP (deglycopeptide levels) in 60 normal (41 men and 19 women; mean age 53 years; range 32–74 years), 35 LC (23 men and 12 women; mean age 56 years; range 43–78 years; HBV-related), and 60 HCC subjects (42 men and 18 women; mean age 58 years; range 38–76 years; HBV-related; 30 stage I, 15 stage II, and 10 stage III). By MRM-MS analysis, the nonglycopeptide had 56.7% sensitivity, 68.3% specificity, and an AUC of 0.687 [cutoff value: ≥0.02 (light/heavy ratio)], comparing the normal and HCC group, whereas the deglycopeptide had 93.3% sensitivity, 68.3% specificity, and an AUC of 0.859 [cutoff value: ≥0.02 (light/heavy ratio)]. In comparing the stage I HCC subgroup with the LC group, the nonglycopeptide had a sensitivity of 66.7%, specificity of 80.0%, and an AUC of 0.712 [cutoff value: ≥0.02 (light/heavy ratio)], whereas the deglycopeptide had a sensitivity of 96.7%, specificity of 80.0%, and an AUC of 0.918 [cutoff value: ≥0.02 (light/heavy ratio)]. These data demonstrate that the discriminatory power of the deglycopeptide is greater than that of the nonglycopeptide. We conclude that deglycopeptide can distinguish cancer status between normal subjects and HCC patients better than nonglycopeptide. PMID:25310463

  18. 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

  19. Rapid falls in maternal serum alpha-fetoprotein concentrations.

    PubMed Central

    Bredow, M T; Goldie, D J

    1985-01-01

    The pronounced falls in AFP concentration sometimes seen in samples taken for screening in early pregnancy are consistent with the range of AFP half lives measured in 14 postpartum women of 59-133 h. PMID:2580865

  20. 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

  1. Engineering of the Saccharomyces cerevisiae yeast strain with multiple chromosome-integrated genes of human alpha-fetoprotein and its high-yield secretory production, purification, structural and functional characterization.

    PubMed

    Dudich, Elena; Dudich, Igor; Semenkova, Lidia; Benevolensky, Sergey; Morozkina, Elena; Marchenko, Aleksey; Zatcepin, Sergey; Dudich, Dmitry; Soboleva, Galina; Khromikh, Luidmila; Roslovtceva, Olga; Tatulov, Eduard

    2012-07-01

    Alpha-fetoprotein (AFP) is a biological drug candidate of high medicinal potential in the treatment of autoimmune diseases, cancer, and regenerative medicine. Large-scale production of recombinant human alpha-fetoprotein (rhAFP) is desirable for structural and functional studies and applied research. In this study we cloned and expressed in the secreted form wild-type glycosylated human rhAFP and non-glycosylated mutant rhAFP(0) (N233S) in the yeast strain Saccharomyces cerevisiae with multiple chromosome-integrated synthetic human AFP genes. RhAFP and rhAFP(0) were successfully produced and purified from the culture liquids active naturally folded proteins. Elimination of the glycosylation by mutation reduced rhAFP(0) secretion about threefold as compared to the wild-type protein showing critical role of the N-linked glycan for heterologous protein folding and secretion. Structural similarity of rhAFP and rhAFP(0) with natural embryonic eAFP was confirmed by circular dichroism technique. Functional tests demonstrated similar type of tumor suppressive and immunosuppressive activity for both recombinant species rhAFP and rhAFP(0) as compared to natural eAFP. It was documented that both types of biological activities attributed to rhAFP and rhAFP(0) are due to the fast induction of apoptosis in tumor cells and mitogen-activated lymphocytes. Despite the fact that rhAFP and rhAFP(0) demonstrated slightly less effective tumor suppressive activity as compared to eAFP but rhAFP(0) had produced statistically notable increase in its ability to induce inhibition of in vitro lymphocyte proliferation as compared to the glycosylated rhAFP and eAFP. We conclude that N-linked glycosylation of rhAFP is required for efficient folding and secretion. However the presence of N-linked sugar moiety was shown to be unimportant for tumor suppressive activity but was critically important for its immunoregulative activity which demonstrates that different molecular mechanisms are involved

  2. Characterization of alpha-fetoprotein levels in three dolphin species: development of sensitive immunoassays for analysis of the pregnancy-associated variations.

    PubMed

    Morita, Yuka; Hiramatsu, Naoshi; Fujita, Toshiaki; Amano, Haruna; Katsumata, Etsuko; Arai, Kazutoshi; Iwasaki, Toshihide; Todo, Takashi; Hara, Akihiko

    2013-01-01

    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.

  3. GoldMag nanocomposite-functionalized graphene sensing platform for one-step electrochemical immunoassay of alpha-fetoprotein.

    PubMed

    Zhang, Bing; Tang, Dianping; Liu, Bingqian; Chen, Huafeng; Cui, Yuling; Chen, Guonan

    2011-10-15

    A new flow-through electrochemical immunosensor was designed for sensitive detection of alpha-fetoprotein (AFP) in human serum by using nanogold-functionalized magnetic graphene nanosheets as immunosensing probes. Initially, amino functionalized magnetic beads were covalently immobilized on the surface of graphene oxide nanosheets (MGPs), then nanogold particles were adsorbed on the amino groups of the MGPs to construct GoldMag nanocomposites functionalized graphene nanosheets (GMGPs), and then horseradish peroxidase-anti-AFP conjugates (HRP-anti-AFP) were assembled onto the surface of nanogold particles (bio-GMGP). With the aid of an external magnet, the formed bio-GMGPs were attached onto the base electrode in the flow system. With a non-competitive immunoassay format, the injected sample containing AFP antigens was produced transparent immunoaffinity reaction with the immobilized HRP-anti-AFP on the bio-GMGPs. The formed immunocomplex inhibited partly the active center of HRP, and decreased the labeled HRP toward the reduction of H(2)O(2). The performance and factors influencing the performance of the immunosensor were investigated in detail. Under optimal conditions, the electrochemical immunosensor displayed a wide working range of 0.01-200 ng mL(-1) with a low detection limit (LOD) of 1.0 pg mL(-1) AFP (at 3s(B)). Intra- and inter-assay coefficients of variation (CV) were below 10%. In addition, the methodology was validated with real serum samples, receiving a good correlation with the results obtained from commercially available electrochemiluminescence automated analyzer.

  4. Des-gamma-carboxy Prothrombin and Alpha fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma

    PubMed Central

    Lok, Anna S.; Sterling, Richard K.; Everhart, James E.; Wright, Elizabeth C.; Hoefs, John C.; Di Bisceglie, Adrian M.; Morgan, Timothy R.; Kim, Hae-Young; Lee, William M.; Bonkovsky, Herbert L.; Dienstag, Jules L.

    2009-01-01

    Background and Aims: The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. The aim of this study was to compare the accuracy of alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the early diagnosis of HCC. Methods: Among 1031 patients randomized in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial, a nested case-control study of 39 HCC cases (24 early stage) and 77 matched controls was conducted to compare the performance of AFP and DCP. Testing was performed on sera from 12 months prior (month −12) to the time of HCC diagnosis (month 0). Results: The sensitivity and specificity of DCP at month 0 was 74% and 86% at a cutoff of 40 mAU/mL and 43% and 100% at a cutoff of 150 mAU/mL. The sensitivity and specificity of AFP at month 0 was 61% and 81% at a cutoff of 20 ng/mL and 22% and 100% at a cutoff of 200 ng/mL. At month −12, the sensitivity and specificity at the low cutoff was 43% and 94% for DCP and 47% and 75% for AFP. Combining both markers increased the sensitivity to 91% at month 0 and 73% at month 12 but the specificity decreased to 74% and 71%. Diagnosis of early HCC was triggered by surveillance ultrasound in 14, doubling of AFP in 5 and combination of tests in 5 patients. Conclusions: Biomarkers are needed to complement ultrasound in the detection of early HCC but neither DCP nor AFP is optimal. PMID:19852963

  5. 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).

  6. Horseradish peroxidase functionalized gold nanorods as a label for sensitive electrochemical detection of alpha-fetoprotein antigen.

    PubMed

    Guo, Jinjin; Han, Xiaowei; Wang, Junchun; Zhao, Junqing; Guo, Zilin; Zhang, Yuzhong

    2015-12-15

    In this study, a novel tracer, horseradish peroxidase (HRP) functionalized gold nanorods (Au NRs) nanocomposites (HRP-Au NRs), was designed to label the signal antibodies for sensitive electrochemical measurement of alpha-fetoprotein (AFP). The preparation of HRP-Au NRs nanocomposites and the labeling of secondary antibody (Ab2) were performed by one-pot assembly of HRP and Ab2 on the surface of Au NRs. The immunosensor was fabricated by assembling carbon nanotubes (CNTs), Au NRs, and capture antibodies (Ab1) on the glassy carbon electrode. In the presence of AFP antigen, the labels were captured on the surface of the Au NRs/CNTs via specific recognition of antigen-antibody, resulting in the signal intensity being clearly increased. Differential pulse voltammetry (DPV) was employed to record the response signal of the immunosensor in phosphate-buffered saline (PBS) containing hydrogen peroxide (H2O2) and 3,3',5,5'-tetramethylbenzidine (TMB). Under optimal conditions, the signal intensity was linearly related to the concentration of AFP in the range of 0.1-100 ng ml(-1), and the limit of detection was 30 pg ml(-1) (at signal/noise [S/N] = 3). Furthermore, the immunoassay method was evaluated using human serum samples, and the recovery obtained was within 99.0 and 102.7%, indicating that the immunosensor has potential clinical applications.

  7. Ultrasensitive Label-free Electrochemical Immunosensor based on Multifunctionalized Graphene Nanocomposites for the Detection of Alpha Fetoprotein

    PubMed Central

    Wang, Yaoguang; Zhang, Yong; Wu, Dan; Ma, Hongmin; Pang, Xuehui; Fan, Dawei; Wei, Qin; Du, Bin

    2017-01-01

    In this work, a novel label-free electrochemical immunosensor was developed for the quantitative detection of alpha fetoprotein (AFP). Multifunctionalized graphene nanocomposites (TB-Au-Fe3O4-rGO) were applied to modify the electrode to achieve the amplification of electrochemical signal. TB-Au-Fe3O4-rGO includes the advantages of graphene, ferroferric oxide nanoparticles (Fe3O4 NPs), gold nanoparticles (Au NPs) and toluidine blue (TB). As a kind of redox probe, TB can produce the electrochemical signal. Graphene owns large specific surface area, high electrical conductivity and good adsorption property to load a large number of TB. Fe3O4 NPs have good electrocatalytic performance towards the redox of TB. Au NPs have good biocompatibility to capture the antibodies. Due to the good electrochemical performance of TB-Au-Fe3O4-rGO, the effective and sensitive detection of AFP was achieved by the designed electrochemical immunosensor. Under optimal conditions, the designed immunosensor exhibited a wide linear range from 1.0 × 10−5 ng/mL to 10.0 ng/mL with a low detection limit of 2.7 fg/mL for AFP. It also displayed good electrochemical performance including good reproducibility, selectivity and stability, which would provide potential applications in the clinical diagnosis of other tumor markers. PMID:28186128

  8. The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization

    PubMed Central

    Liu, Lei; Zhao, Yan; Jia, Jia; Chen, Hui; Bai, Wei; Yang, Man; Yin, Zhanxin; He, Chuangye; Zhang, Lei; Guo, Wengang; Niu, Jing; Yuan, Jie; Cai, Hongwei; Xia, Jielai; Fan, Daiming; Han, Guohong

    2016-01-01

    This retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [ΔAFP(%)] greater than the cutoff point. The ΔAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2–66.9). A level of 46% was chosen as the threshold value for ΔAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG ≥ 1 (HR = 1.95; 95% CI 1.24–3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15–2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy. PMID:26831408

  9. Dendritic cells pulsed with alpha-fetoprotein and mutant P53 fused gene induce bi-targeted cytotoxic T lymphocyte response against hepatic carcinoma.

    PubMed

    Ren, Jun; Jia, Jun; Zhang, Hongmei; Zhang, Liwang; Ma, Bo; Jiang, Hanfang; Di, Lijun; Song, Guohong; Yu, Jing

    2008-07-01

    Dendritic cell (DC)-based immunotherapy is rapidly emerging as a promising treatment in cancer therapy. We had previously shown that DC pulsed with either defined mRNA of tumor antigen (Ag) such as alpha-fetoprotein (AFP), or total RNA of hepatocellular carcinoma (HCC) could elicit Ag-specific cytotoxic T lymphocyte (CTL) response. Therefore, we suggested a novel DC-based therapeutic method, in which DCs derived from CD34(+) cells enriched peripheral blood mononuclear cells were pulsed with liposome-coated AFP and mutant P53 (mtP53) fused gene pEGFP-C3/AFP-mtP53 to induce bi-targeted specific CTL responses against HCC. Three different genotype HCC cell lines, HepG2 (human histocompatibility leukocyte antigens (HLA) A2 positive, AFP expressing positive, P53 expressing negative), SMMC7721 (HLA A2 positive, neither AFP nor P53 expressing positive), and HMCC97 (HLA A2 positive, both AFP and P53 expressing positive) were selected as targets for CTL responses. An important finding was that DCs pulsed with the liposome-coated fused gene could evoke more intensive bi-targeted Ag-specific CTL responses against HMCC97 than DCs pulsed with either AFP or P53 single gene (P < 0.05). This experimental therapeutic model provides a new promising cytotherapeutic approach, in that DCs pulsed with the fused gene of different Ags might induce more extensive multitargeted antitumor immunity.

  10. Fine specificity analysis of an HLA-A2.1-restricted immunodominant T cell epitope derived from human alpha-fetoprotein.

    PubMed

    Meng, W S; Butterfield, L H; Ribas, A; Heller, J B; Dissette, V B; Glaspy, J A; McBride, W H; Economou, J S

    2000-11-01

    Human alpha-fetoprotein (AFP) is a potentially important target for the immunotherapy of hepatocellular carcinoma (HCC). AFP(542-550) (GVALQTMKQ) is one of several HLA-A2.1-restricted immunodominant AFP peptides that consistently generate AFP-specific T cell responses in human T cell cultures and in HLA-A2.1/K(b) transgenic (A2.1 tg) mice. We performed a fine specificity analysis of this nonamer to determine which amino acid side chains were critical for T cell priming and recognition. Using peptide-pulsed dendritic cells (DC) as an immunization strategy, we characterized the effects of AFP(542-550) amino acid substitutions on priming and recognition in A2.1 tg mice. Replacing the glutamine at anchor position 9 with a leucine enhanced MHC binding and AFP-specific T cell responses. Substitution of leucine at non-anchor position 4 with an alanine did not alter binding but greatly diminished T cell recognition. Computer-generated three-dimensional models provided the structural rationale for these observed effects in MHC binding and T cell responses resulted from the modifications in the AFP(542-550) sequence.

  11. Maternal serum alpha-fetoprotein levels in pregnancies complicated by diabetes: implications for screening programs.

    PubMed

    Martin, A O; Dempsey, L M; Minogue, J; Liu, K; Keller, J; Tamura, R; Freinkel, N

    1990-10-01

    Maternal serum alpha-fetoprotein may be reduced in diabetic pregnancies, but the association with elevated glycosylated hemoglobin has been controversial. We tested the hypothesis that reductions in maternal serum alpha-fetoprotein may reflect the same phenomena that can also impair normal rates of embryo growth in the presence of poorly compensated maternal diabetes. If so, associations would be expected among maternal serum alpha-fetoprotein, embryo rates of growth, and levels of glycosylated hemoglobin reflective of regulation of maternal diabetes during the period of organogenesis. We found maternal serum alpha-fetoprotein levels in 93 pregnant patients with diabetes to be negatively associated with the earliest (4 to 12 weeks) glycosylated hemoglobin determinations. At glycosylated hemoglobin values greater than 9.6% (which approximates the upper quartile), all maternal serum alpha-fetoprotein values fell below the median for patients without diabetes (below 0.8 multiple of the median after weight adjustment). Moreover, there was a trend for pregnancies with lower maternal serum alpha-fetoprotein levels and higher glycosylated hemoglobin values to also demonstrate early fetal growth delay as measured by ultrasonography.

  12. 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.

  13. [Determination of alpha-fetoprotein in the serum of pregnant women by rocket-linear immunoelectrophoresis].

    PubMed

    Demchenko, T V; Shevtsova, A I; Berezin, V A; Voronin, K V; Usenko, L V

    1986-01-01

    Rocket-linear immunoelectrophoresis enabled to estimate the alpha-fetoprotein content in blood serum of pregnant women. Sensitivity of the procedure constituted as low as 13-22 ng of the protein per I ml of blood serum. Concentration of the protein in blood serum depended on the period of pregnancy; middle values of normal content of alpha-fetoprotein in blood serum were estimated within various periods of pregnancy in women of the district studied. The procedure might be used simultaneously with immunoenzymatic and radioimmune methods in prenatal diagnosis of impairments in development of the fetus neural tube.

  14. Screening for Down's syndrome using serum alpha fetoprotein: a retrospective study indicating caution.

    PubMed Central

    Spencer, K; Carpenter, P

    1985-01-01

    A report was made on the outcome of a four year retrospective study in 27 064 pregnancies, of the clinical efficiency, sensitivity, and specificity of a screening programme for Down's syndrome based on reported strategies related to the measurement of maternal serum alpha fetoprotein. This study identified 27 pregnancies affected by Down's syndrome with a median multiple of the median maternal serum alpha fetoprotein concentration of 0.82. This figure is considerably higher than that obtained from previous reports on this subject. With an age related multiple of the median maternal serum alpha fetoprotein strategy, 30.8% of Down's affected pregnancies were identified as well as 11.6% of unaffected pregnancies. Perhaps a United Kingdom collaborative study should begin to investigate the reasons for such wide population variance in the reports for the median multiple of the median for Down's affected pregnancies. Until such studies are carried out, screening for Down's syndrome based on low maternal serum alpha fetoprotein concentration is premature. PMID:2408699

  15. Serum alpha-fetoprotein subfractions identified by Ricinus communis agglutinin I in hepatic malignancies, yolk sac tumor, benign hepatic diseases, and fetal stage.

    PubMed

    Ishiguro, T; Takahashi, Y

    1989-01-01

    Using Ricinus communis agglutinin I (RCA-I) affinity crossed-line immunoelectrophoresis, alpha-fetoprotein (AFP) subfractions were studied in sera from patients with primary hepatic cancer (PHC), hepatic metastasis of gastric cancer (HMGC), yolk sac tumor (YST), acute or chronic hepatitis or hepatic cirrhosis. Fetal AFP subfractions were also examined in amniotic fluids or in culture fluids of fetal tissues. RCA-I non-reactive subfraction was commonly found in PHC, HMGC, YST, benign hepatic diseases, and fetal stage. RCA-I weakly reactive (WR) or strongly reactive (SR) subfraction was noted only in malignant diseases. RCA-I has a specific affinity to terminal galactose in oligosaccharide, and the presence of sialic acid on galactose residue(s) inhibits the affinity with RCA-I. Therefore, common AFP subfraction non-reactive with RCA-I was assumed to be galactosialyl form, while RCA-I WR and SR subfractions found only in malignancies were monogalactosyl and digalactosyl, respectively. Clinically this approach to detect the RCA-I WR or SR subfraction facilitates a differential diagnosis of AFP-producing malignancies and benign conditions.

  16. Prussian blue-gold nanoparticles-ionic liquid functionalized reduced graphene oxide nanocomposite as label for ultrasensitive electrochemical immunoassay of alpha-fetoprotein.

    PubMed

    Gao, Qi; Liu, Na; Ma, Zhanfang

    2014-06-04

    In this work, poly(diallyldimethylammonium chloride) (PDDA) protected Prussian blue/gold nanoparticles/ionic liquid functionalized reduced graphene oxide (IL-rGO-Au-PDDA-PB) nanocomposite was fabricated. The resulting nanocomposite exhibited high biocompatibility, conductivity and catalytic activity. To assess the performance of the nanocomposite, a sensitive sandwich-type immunosensor was constructed for detecting alpha-fetoprotein (AFP). Greatly enhanced sensitivity for this immunosensor was based on triple signal amplification strategies. Firstly, IL-rGO modified electrode was used as biosensor platform to capture a large amount of antibody due to its increased surface area, thus amplifying the detection response. Secondly, a large number of Au-PDDA-PB was conjugated on the surface of IL-rGO, which meant the enrichment of the signal and the more immobilization of label antibody. Finally, the catalytic reaction between H2O2 and the IL-rGO-Au-PDDA-PB nanocomposite further enhanced the signal response. The signals increased linearly with AFP concentrations in the range of 0.01-100 ng mL(-1). The detection limit for AFP was 4.6 pg mL(-1). The immunosensor showed high sensitivity, excellent selectivity and good stability. Moreover, the immunosensor was applied to the analysis of AFP in serum sample with satisfactory result.

  17. 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.

  18. A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel.

    PubMed

    Ji, Xiaonan; Shen, Yanli; Sun, Hao; Gao, Xiangdong

    2016-08-01

    Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.

  19. 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

    2015-09-03

    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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. [Study of the content of alpha-fetoprotein and serum albumin in the vitreous body of the eye of human embryos].

    PubMed

    Panova, I G; Tatikolov, A S

    2011-01-01

    The content of serum albumin and alpha-fetoprotein in the vitreous body of the eyes of human embryos from the 16th through the 24th week was investigated. It was detected that albumin and alpha-fetoprotein in the vitreous body of human eyes are presented in equal molar concentrations in the 16th week. There is 1.5-fold increased concentration of alpha-fetoprotein in comparison to albumin during the 17th week. Seventeen weeks later, there was a reduction in the concentration of both proteins. It was reported that cyanine dye, used for detection of albumin, does not interact with alpha-fetoprotein.

  8. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

    PubMed Central

    Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernández-Pedro, Norma

    2007-01-01

    Background Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. Methods We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. Results For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. Conclusion The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng

  9. Focal nodular hyperplasia of the liver and elevated alpha fetoprotein level in an infant with isolated hemihyperplasia.

    PubMed

    Demir, Hac Ahmet; Varan, Ali; Akçören, Zuhal; Haliloglu, Mithat; Büyükpamukcu, Münevver

    2008-10-01

    A case of focal nodular hyperplasia of the liver in a 43-day-old baby girl with isolated hemihyperplasia and elevated serum alpha-fetoprotein is presented. The child referred to our hospital with bilateral renal masses detected by prenatal and postnatal ultrasonography. A mass lesion was detected in segment 6 of liver and was diagnosed as focal nodular hyperplasia. We present this case to emphasize the presence of focal nodular hyperplasia in a patient with isolated hemihypertrophy and elevated serum alpha-fetoprotein level.

  10. The Evolution of the Use of Serum Alpha-fetoprotein in Clinical Liver Cancer Surveillance

    PubMed Central

    Kelly, Sarah-Louise; Bird, Thomas G

    2017-01-01

    Liver cancer is the 6th most common cancer and 2nd leading cause of cancer-related mortality. In order to improve patient survival early tumor detection is required and this necessitates accurate screening of at risk individuals. In this article we concisely review the methodologies employed for Hepatocellular Carcinoma (HCC) surveillance and how their use has evolved over the last three decades. We focus attention to serum biomarkers, particularly alpha-fetoprotein. We propose that by using an increasingly sophisticated approach to assess dynamic rates of change in biomarkers tailored to individual patients that screening accuracy may be improved. Additional improvements may also be possible by the incorporation of patient clinical data into such personalised screening assessments. These possibilities may hold the promise of improving cancer detection and early curative therapy for the increasing worldwide population at risk of HCC development. PMID:28133640

  11. Familial synchronous bilateral teratoid Wilms tumor with elevated alpha-fetoprotein level.

    PubMed

    Okur, Arzu; Pinarli, Faruk Guclu; Karadeniz, Ceyda; Poyraz, Aylar; Fidan, Kibriya; Basaklar, Can; Oguz, Aynur

    2012-11-01

    Familial Wilms tumor is a rare entity that accounts for only 1-2% of all Wilms tumor cases, with an earlier age of onset and an increased frequency of bilateral tumors. Teratoid Wilms tumor is a variant of nephroblastoma with a predominance of heterologous tissues comprising more than 50% of the tumor volume. Wilms tumor does not usually secrete any specific tumor marker and all teratoid Wilms tumor cases previously reported were sporadic non-secreting neoplasms. Here we describe an infant with familial synchronous bilateral teratoid Wilms tumor whose serum alpha-fetoprotein level was elevated. To our knowledge, this extremely rare type of case is reported for the first time in the literature.

  12. Prevalence of elevated anticardiolipin antibodies in pregnant women with unexplained elevations of alpha-fetoprotein.

    PubMed

    Yetman, D L; Kutteh, W H; Castorena, R; Brown, C; Baskin, L

    1997-04-01

    The goal was to determine what proportion of pregnant women with unexplained elevations of maternal serum alpha-fetoprotein (MSAFP) have increased levels of anticardiolipin antibodies (ACA), and if this might explain the increased prevalence of adverse pregnancy outcomes. Maternal serum alpha-fetoprotein levels of 12,295 pregnant women were evaluated at 15-19.5 gestational weeks. Elevated readings (> 2.5 MOM) were identified in 190 women (1.5%) and 86 (0.7%) of these had unexplained causes. Specimens (80) were recovered and ACA levels for cardiolipin were determined using enzyme-linked immunosorbant assay. Positive IgG ACA were identified in 10 out of 80 cases (12.5%) of elevated MSAFP; 3 out of 80 cases (3.8%) had positive IgM ACA. The control women with normal MSAFP levels had positive IgG ACA in 3 of 86 cases (3.5%) and 1 of 86 cases (1.2%) for IgM. Women with increased MSAFP and positive ACA had infants with an average birth weight of 2684 +/- 889 g compared to 2793 +/- 847 g in women with increased MSAFP and normal ACA. No significant differences in IgG ACA were found in pregnant women with unexplained elevated MSAFP (10/80, 12.5%) compared to women with normal MSAFP (3/86, 3.5%). As expected, lower birth weight was identified in women who had elevated MSAFP (2738 +/- 868 g) vs. women with normal MSAFP 3181 +/- 1082 g (P = 0.004), independent of ACA positivity.

  13. Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation.

    PubMed

    Lai, Quirino; Avolio, Alfonso W; Graziadei, Ivo; Otto, Gerd; Rossi, Massimo; Tisone, Giuseppe; Goffette, Pierre; Vogel, Wolfgang; Pitton, Michael B; Lerut, Jan

    2013-10-01

    Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010. A prospectively collected database originating from 6 collaborating European centers was used for the study. Sixty-one patients (14.5%) developed HCC recurrence. For both MC-IN and MC-OUT patients, an AFP slope > 15 ng/mL/month and mRECIST progression were unique independent risk factors for HCC recurrence and patient death. When the radiological Milan criteria (MC) status was combined with radiological and biological progression, MC-IN and MC-OUT patients without risk factors had similarly excellent 5-year tumor-free and patient survival rates. MC-IN patients with at least 1 risk factor had worse outcomes, and MC-OUT patients with at least 1 risk factor had the poorest survival (P < 0.001). In conclusion, both radiological and biological modifications permit documentation of the response to LRT in patients waiting for LT. According to these 2 parameters, tumor progression significantly increases the risk of recurrence and patient death not only for MC-OUT patients but also for MC-IN patients. The monitoring of both parameters in combination with the initial radiological MC status is an essential element for further refining the selection criteria for potential liver recipients with HCC.

  14. Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma.

    PubMed

    Park, Sang Joon; Jang, Jae Young; Jeong, Soung Won; Cho, Young Kyu; Lee, Sae Hwan; Kim, Sang Gyune; Cha, Sang-Woo; Kim, Young Seok; Cho, Young Deok; Kim, Hong Soo; Kim, Boo Sung; Park, Suyeon; Bang, Hae In

    2017-03-01

    Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). This study compared the diagnostic values of AFP, AFP-L3, and PIVKA-II individually and in combination to find the best biomarker or biomarker panel.Seventy-nine patients with newly diagnosed HCC and 77 non-HCC control patients with liver cirrhosis were enrolled. AFP, AFP-L3, and PIVKA-II were measured in the same serum samples using microchip capillary electrophoresis and a liquid-phase binding assay on an automatic analyzer. Receiver-operating characteristic curve analyses were also applied to all combinations of the markers.When the 3 biomarkers were analyzed individually, AFP showed the largest area under the receiver-operating characteristic curve (AUC) (0.751). For combinations of the biomarkers, the AUC was highest (0.765) for "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL." The combination of "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL and AFP-L3 > 10%" had worse sensitivity and lower AUC (P = 0.001). The highest AUC of a single biomarker was highest for AFP and of a combination was "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL," with this also being the case when the cut-off value of AFP and AFP-L3 was changed.Alpha-fetoprotein showed the best diagnostic performance as a single biomarker for HCC. The diagnostic value of AFP was improved by combining it with PIVKA-II, but adding AFP-L3 did not contribute to the ability to distinguish between HCC and non-HCC liver cirrhosis. These findings were not altered when the cut-off value of AFP and AFP-L3 was changed.

  15. Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma

    PubMed Central

    Park, Sang Joon; Jang, Jae Young; Jeong, Soung Won; Cho, Young Kyu; Lee, Sae Hwan; Kim, Sang Gyune; Cha, Sang-Woo; Kim, Young Seok; Cho, Young Deok; Kim, Hong Soo; Kim, Boo Sung; Park, Suyeon; Bang, Hae In

    2017-01-01

    Abstract Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). This study compared the diagnostic values of AFP, AFP-L3, and PIVKA-II individually and in combination to find the best biomarker or biomarker panel. Seventy-nine patients with newly diagnosed HCC and 77 non-HCC control patients with liver cirrhosis were enrolled. AFP, AFP-L3, and PIVKA-II were measured in the same serum samples using microchip capillary electrophoresis and a liquid-phase binding assay on an automatic analyzer. Receiver-operating characteristic curve analyses were also applied to all combinations of the markers. When the 3 biomarkers were analyzed individually, AFP showed the largest area under the receiver-operating characteristic curve (AUC) (0.751). For combinations of the biomarkers, the AUC was highest (0.765) for “PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL.” The combination of “PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL and AFP-L3 > 10%” had worse sensitivity and lower AUC (P = 0.001). The highest AUC of a single biomarker was highest for AFP and of a combination was “PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL,” with this also being the case when the cut-off value of AFP and AFP-L3 was changed. Alpha-fetoprotein showed the best diagnostic performance as a single biomarker for HCC. The diagnostic value of AFP was improved by combining it with PIVKA-II, but adding AFP-L3 did not contribute to the ability to distinguish between HCC and non-HCC liver cirrhosis. These findings were not altered when the cut-off value of AFP and AFP-L3 was changed. PMID:28296720

  16. Sublingual vein parameters, AFP, AFP-L3, and GP73 in patients with hepatocellular carcinoma.

    PubMed

    Zhao, J; Guo, L-Y; Yang, J-M; Jia, J-W

    2015-06-26

    This study evaluated the diagnostic value of alpha-fetoprotein (AFP), AFP heterogeneity 3 (AFP-L3), Golgi protein 73 (GP73), and sublingual vein parameters in hepatocellular carcinoma (HCC). Levels of serum AFP, AFP-L3, GP73, and sublingual vein scores were measured in 34 patients with chronic hepatitis, 65 patients with post-hepatitis B cirrhosis, 71 patients with HCC, and 6 healthy controls. Logistic regression analysis was used to explore potential correlations. Sublingual vein grades in patients with HCC were higher than those in the other three groups; sublingual vein scores were also different between groups; combined diagnosis using AFP, GP73, and sublingual vein grade was superior to the individual parameters alone or when only two were used in different combinations. Thus, sublingual vein grade can be considered as an independent risk factor for diagnosis of HCC. Furthermore, combined detection with AFP, GP73, and sublingual vein grade is simple, inexpensive, and effective. It may therefore be suitable for screening high-risk populations for early diagnosis of HCC.

  17. Molecular Analysis of AFP and HSA Interactions with PTEN Protein.

    PubMed

    Zhu, Mingyue; Lin, Bo; Zhou, Peng; Li, Mengsen

    2015-01-01

    Human cytoplasmic alpha-fetoprotein (AFP) has been classified as a member of the albuminoid gene family. The protein sequence of AFP has significant homology to that of human serum albumin (HSA), but its biological characteristics are vastly different from HSA. The AFP functions as a regulator in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway, but HSA plays a key role as a transport protein. To probe their molecular mechanisms, we have applied colocalization, coimmunoprecipitation (co-IP), and molecular docking approaches to analyze the differences between AFP and HSA. The data from colocalization and co-IP displayed a strong interaction between AFP and PTEN (phosphatase and tensin homolog), demonstrating that AFP did bind to PTEN, but HSA did not. The molecular docking study further showed that the AFP domains I and III could contact with PTEN. In silicon substitutions of AFP binding site residues at position 490M/K and 105L/R corresponding to residues K490 and R105 in HSA resulted in steric clashes with PTEN residues R150 and K46, respectively. These steric clashes may explain the reason why HSA cannot bind to PTEN. Ultimately, the experimental results and the molecular modeling data from the interactions of AFP and HSA with PTEN will help us to identify targets for designing drugs and vaccines against human hepatocellular carcinoma.

  18. Engineered cytotoxic T lymphocytes with AFP-specific TCR gene for adoptive immunotherapy in hepatocellular carcinoma.

    PubMed

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

    2016-01-01

    Alpha-fetoprotein (AFP) is overexpressed in hepatocellular carcinoma (HCC) and could serve as a tumor-associated antigen (TAA) and potential target for adoptive immunotherapy. However, low frequency and severe functional impairment of AFP-specific T cells in vivo hamper adoptive infusion. TAA-specific T cell receptor (TCR) gene transfer could be an efficient and reliable alternation to generate AFP-specific cytotoxic T lymphocytes (CTLs). Autologous dendritic cells (DC) pulsed with AFP158-166 peptides were used to stimulate AFP-specific CTLs. TCR α/β chain genes of AFP-specific CTLs were cloned and linked by 2A peptide to form full-length TCR coding sequence synthesized into a lentiviral vector. Nonspecific activated T cells were engineered by lentivirus infection. Transgenetic CTLs were evaluated for transfection efficiency, expression of AFP158-166-specific TCR, interferon (IFN)-γ secretion, and specific cytotoxicity toward AFP+ HCC cells in vitro and in vivo. Flow cytometry revealed the AFP158-166-MHC-Pentamer positive transgenetic CTLs was 9.86 %. The number of IFN-γ secretion T cells and the specific cytotoxicity toward HpeG2 in vitro and in tumor-bearing NOD/SCID mice were significantly raised in transgenetic CTLs than that of AFP158-166-specific CTLs obtained by peptide-pulsed DCs or control group. TCR gene transfer is a promising strategy to generate AFP158-166-specific CTLs for the treatment of HCC.

  19. Maternal and Fetal Mechanisms of B Cell Regulation during Pregnancy: Human Chorionic Gonadotropin Stimulates B Cells to Produce IL-10 While Alpha-Fetoprotein Drives Them into Apoptosis

    PubMed Central

    Fettke, Franziska; Schumacher, Anne; Canellada, Andrea; Toledo, Natalia; Bekeredjian-Ding, Isabelle; Bondt, Albert; Wuhrer, Manfred; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2016-01-01

    Maternal immune tolerance toward the fetus is an essential requisite for pregnancy. While T cell functions are well documented, little is known about the participation of B cells. We have previously suggested that IL-10-producing B cells are involved in pregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblasts positively regulate the generation of IL-10-producing B cells. We next studied the participation of hormones produced by the placenta as well as the fetal protein alpha-fetoprotein (AFP) in B cell modulation. Human chorionic gonadotropin (hCG), but not progesterone, estrogen, or a combination of both, was able to promote changes in B cell phenotype and boost their IL-10 production, which was abolished after blocking hCG. The hCG-induced B cell phenotype was not associated with augmented galactosylation, sialylation, or fucosylation of IgG subclasses in their Fc. In vitro, hCG induced the synthesis of asymmetrically glycosylated antibodies in their Fab region. Interestingly, AFP had dual effects depending on the concentration. At concentrations corresponding to maternal serum levels, it did not modify the phenotype or IL-10 secretion of B cells. At fetal concentrations, however, AFP was able to drive B cells into apoptosis, which may indicate a protective mechanism to avoid maternal B cells to reach the fetus. Our data suggest that the fetus secrete factors that promote a pregnancy-friendly B cell phenotype, unraveling interesting aspects of B cell function, and modulation by pregnancy hormones and fetal proteins. PMID:28008329

  20. Stem cells from human exfoliated deciduous teeth differentiate into functional hepatocyte-like cells by herbal medicine.

    PubMed

    Su, Wen-Ta; Chen, Xiao-Wei

    2014-01-01

    Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells isolated from the exfoliated human deciduous incisor that can differentiate into a many cell types. In this study, we evaluated the effect of liquorice or angelica extracts on the hepatic differentiation potential of SHEDs cells. SHEDs cells cultured in medium containing liquorice extracts were analyzed for 1) changes in cellular morphology, 2) changes in hepatic gene expression, AFP (Alpha-fetoprotein) and ALB (Albumin), and 3) albumin secretion and urea synthesis activity. Our data show that the hepatic differentiation potential of SHEDs cells is enhanced by the presence of liquorice or angelica extracts in the culture medium. Our findings present new therapeutic possibilities for liver damage repair.

  1. Affinity partitioning of albumin and alpha-fetoprotein in an aqueous two-phase system using poly(ethylene glycol)-bound triazine dyes.

    PubMed

    Birkenmeier, G; Usbeck, E; Kopperschläger, G

    1984-01-01

    Human albumin and alpha-fetoprotein are partitioned in an aqueous two-phase system composed of 10% (w/w) Dextran and 7.5% (w/w) poly(ethylene glycol). When a small amount of poly(ethylene glycol) is replaced by Cibacron Blue F3G-A-liganded poly(ethylene glycol) the partition coefficient, K, of albumin increases by the factor of about 4000 whereas the K value of alpha-fetoprotein undergoes only a small change. The change of the partition coefficient in a logarithmic scale induced by increasing dye-polymer concentrations turned out as a useful measure for the affinity of albumin and alpha-fetoprotein to the dyes. The effect of pH and salt concentration on the affinity partition of albumin and alpha-fetoprotein is demonstrated. The partition of the two proteins in presence of Cibacron Blue F3G-A-liganded poly(ethylene glycol) is compared with seven other triazine dye-poly(ethylene glycol) derivatives.

  2. Ovarian Sertoli-Leydig cell tumor with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review

    PubMed Central

    Horta, Mariana; Cunha, Teresa Margarida; Marques, Rita Canas; Félix, Ana

    2014-01-01

    Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alpha-fetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrine-inactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker. PMID:25926909

  3. 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.

  4. [Importance of the conjugated antibody for the induction of selective effect of adriamycin conjugated with anti AFP monoclonal antibody and entrapped in liposomes against AFP producing tumors].

    PubMed

    Konno, H; Kumai, K; Tsubouchi, T; Ishibiki, K; Abe, O; Tadakuma, T; Yasuda, T; Nagaike, K; Hosokawa, S; Sakaguchi, S

    1989-06-01

    We investigated experimentally the effect of adriamycin (ADM) conjugated with anti alpha-fetoprotein (AFP) monoclonal antibodies and entrapped in liposomes (Lip-ADM = AbAFP) in vitro or in vivo. In the present study, we examined the importance of the conjugated antibody for the induction of selective therapeutic effect of Lip-ADM = AbAFP against AFP producing tumors. As the target tumors, AFP producing human hepatoma strain, Li-7, and AFP non-producing human breast cancer strain, MX-1 maintained in BALB/c nu/nu male mice were used. In order to evaluate the importance of the conjugated antibody, we prepared also ADM conjugated with normal mouse IgG, and entrapped in liposomes Lip-ADM = NIgG, of which therapeutic effects were compared with that of Lip-ADM = AbAFP. Judging from the tumor growth curve and the tumor weight, the therapeutic effect of Lip-ADM = AbAFP was greater against Li-7 than that of Lip-ADM = NIgG. On the other hand, both conjugates showed similar effects against MX-1. As the results it is suggested that the antibody which recognizes the antigen expressed on the target tumor cells can solely increase the therapeutic effect of ADM entrapped in liposomes (Lip-ADM) and that the main factors which contribute to the efficient therapeutic effect of the conjugate were the sensitibility to ADM, the affinity of the tumor cells to liposomes and the superiority of the conjugated antibody.

  5. Artificial antigen-presenting cells expressing AFP(158-166) peptide and interleukin-15 activate AFP-specific cytotoxic T lymphocytes.

    PubMed

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

    2016-04-05

    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 AFP(158-166)-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 AFP(158-166) 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.

  6. Participation of small intraportal stem cells in the restitutive response of the liver to periportal necrosis induced by allyl alcohol.

    PubMed

    Yavorkovsky, L; Lai, E; Ilic, Z; Sell, S

    1995-06-01

    To determine the involvement of different hepatocyte populations in response to periportal injury, the restitutive response to allyl alcohol (AA) injury was examined. Adult female Sprague-Dawley rats were injected intraperitoneally (IP) with 0.62 mmol/kg AA, killed at 6, 9, 12, 33, 57, 81, and 153 hours after injection, and the livers were examined for injury and for restitutive proliferation by histology, autoradiography, and immunohistochemistry to detect alpha-fetoprotein (AFP), glutathione-s-transferase-p (GST-p), desmin, leukocyte common antigen, albumin, and monoclonal antibodies to liver cells: OV-6, H-4, and T-6. AA produces variable periportal liver necrosis predominantly at 6 to 12 hours. Proliferation of hepatocytes throughout the hepatic cord is seen early after injury in nonnecrotic areas: predominantly in zone II, but also in zones I and III, including some cells adjacent to the central vein. Within 2 to 3 days the necrotic zones are filled with small cells and by 1 week the liver architecture is essentially restored. During the active restitutive reaction from the immediate periportal rim the following cell phenotypes are seen: null cells: -->(AFP+, OV-6-, GST-p-) cells-->(AFP-, OV-6+, GST-p+) cells-->large (AFP-, OV-6-, GST-p-, H-4+) liver cells. Albumin staining was negative. We conclude that restitutive proliferation of periportal necrosis induced by AA appears to be accomplished by proliferation of intraportal (?stem) cells whose progeny differentiate and eventually repopulate the necrotic zone.

  7. Lentivirally Engineered DC activate AFP-specific T cells which Inhibit Hepatocellular Carcinoma Growth in vitro and in vivo

    PubMed Central

    Liu, Yang; Butterfield, Lisa H.; Fu, Xiaohui; Song, Zhenshun; Zhang, Xiaoping; Lu, Chongde; Ding, Guanghui; Wu, Mengchao

    2012-01-01

    Alpha-fetoprotein (AFP), a tumor-associated antigen for hepatocellular carcinoma (HCC), is an established biomarker for HCC. In this study, we created a lentivirus expressing the AFP antigen and investigated the antitumor activity of AFP-specific CD8+ T cells, with and without CD4+ T cells, which were activated by either AFP peptide-pulsed or Lenti-AFP-engineered DC in vitro and in vivo. AFP-specific T cells could efficiently kill HepG2 HCC cells, and produced IL-2, IFN-γ, TNF-α, perforin and granzyme B, with minimal production of IL-10 (a negative regulator of T cell activation). Both strategies activated AFP-specific T cells, but the lentiviral strategy was superior by several measures. Data also support an impact of CD4+ T cells in supporting anti-tumor activity. In vivo studies in a xenograft HCC tumor model also showed that AFP-specific T cells could markedly suppress HCC tumor formation and morbidity in tumor-bearing nude mice, as well as regulate serum levels of related cytokines and antitumor molecules. In parallel with human in vitro T cell cultures, the in vivo model demonstrated superior anti-tumor effects and Th1-skewing with Lenti-AFP-DC. This study supports the superiority of a full-length antigen lentivirus-based DC vaccine strategy over peptides, and provides new insight into the design of DC-based vaccines. PMID:21491085

  8. 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.

  9. Effects of AFP gene silencing on apoptosis and proliferation of a hepatocellular carcinoma cell line.

    PubMed

    Zhang, Ling; He, Tao; Cui, Hong; Wang, Yunjian; Huang, Changshan; Han, Feng

    2012-08-01

    Alpha fetoprotein (AFP) is an oncoembryonal protein that is highly expressed in the majority of hepatocellular carcinomas. Previous studies have shown that AFP may be involved in multiple cell growth regulating, differentiating, and immunosuppressive activities. We investigated the effects of AFP gene silencing by siRNA on apoptosis and proliferation of hepatocellular carcinoma cell line EGHC-9901, which highly expresses AFP and may serve as an ideal model for investigation of AFP functions. siRNA expressing plasmid targeting the AFP gene was first established and subsequently transfected into hepatocellular carcinoma cell line EGHC-9901; cells were then divided into three groups: siRNA-afp, transfected with AFP-siRNA; siRNA-beta-actin, transfected with siRNA-beta-actin as the positive group; and vector control, transfected with empty vector as the blank control group. After G418 positive clone selection for a couple of weeks, Western blot and RT (reverse transcription)-PCR assay demonstrated that AFP expression was almost completely inhibited by siRNA-afp, which indicates that siRNA expressing plasmid targeting the AFP gene has been successfully established. Furthermore, MTT (methyl thiazolyl tetrazelium) assay showed that cells transfected with siRNA-afp proliferated at a significantly lower speed than the other two groups and flat plate clone formation assay also witnessed less clones with diameters of more than 75 μm in siRNA-afp immunofluorescence indicating that the apoptosis rate of cells transfected with siRNA-afp was significantly higher than the other two groups. Furthermore, flow cytometry manifested approximately 20% more cells of siRNA-afp within G1 phase than those of the negative group, indicating that inhibition of AFP expression may cause G1 phase arrest. Finally, Western blot and RT-PCR assay demonstrated that siRNA-afp induced a higher expression of caspase-3 than the other two groups whereas there was no difference in expression of caspase-8

  10. 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

  11. Effects of AFP-activated PI3K/Akt signaling pathway on cell proliferation of liver cancer.

    PubMed

    Zheng, Lu; Gong, Wei; Liang, Ping; Huang, XiaoBing; You, Nan; Han, Ke Qiang; Li, Yu Ming; Li, Jing

    2014-05-01

    This study aims to investigate effects of alpha-fetoprotein (AFP)-activated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway on hepatocellular carcinoma cell proliferation. Active cirrhosis patients after hepatitis B infection (n = 20) and viral hepatitis patients with hepatocellular carcinoma (HCC) (n = 20) were selected as the subjects of the present study. Another 20 healthy subjects were selected as the control group. The serum AFP expression and liver tissue PI3K and Akt gene mRNA expression were detected. The hepatoma cell model HepG2 which had a stable expression of AFP gene was used. Real-time quantitative PCR and Western blot and other methods were used to analyze the intracellular PI3K and Akt protein levels. Compared with control group and cirrhosis group, the serum AFP levels in HCC group significantly increased, and the tissue PI3K and Akt mRNA expression also significantly increased. HepG2 cells were intervened using AFP, in which the PIK and Akt protein expression significantly increased. After intervention by use of AFP monoclonal antibodies or LY294002 inhibitor, the PIK and Akt protein expression in HepG2 cell was significantly decreased (P < 0.05). AFP can promote the proliferation of hepatoma cells via activation of PI3K/Akt signaling pathway.

  12. 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.

  13. Aplasia cutis congenita in a setting of fetus papyraceus associated with small fetal abdominal circumference and high alpha-fetoprotein and amniotic acetylcholinesterase.

    PubMed

    Mazza, Joni M; Klein, Janice F; Christopher, Kurt; Silverberg, Nanette B

    2015-01-01

    Fetus papyraceus is the fetal death of one or more fetuses in a multiparous pregnancy. The surviving infants can experience extensive aplasia cutis in an H-shaped distribution over the flanks and abdomen as a consequence of the loss of their fetal sibling. We report the case of a monochorionic, diamniotic pregnancy complicated by a single fetal death at 13 weeks of gestational age. Aplasia cutis of the surviving twin was suggested in utero by three criteria: high amniotic and maternal alpha-fetoprotein, detectable acetylcholinesterase, and small abdominal circumference on prenatal ultrasound. This constellation of findings in the setting of fetus papyraceus can be an indicator of aplasia cutis in the surviving fetus.

  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. Combined analysis of AFP and HCCR-1 as an useful serological marker for small hepatocellular carcinoma: a prospective cohort study.

    PubMed

    Zhang, Guoxin; Ha, Seon-Ah; Kim, Hyun K; Yoo, Jinah; Kim, Sanghee; Lee, Youn S; Hur, Soo Y; Kim, Yong W; Kim, Tae E; Park, Yong G; Wang, Jing; Yang, Yang; Xu, Zekuan; Song, Eun Y; Huang, Zuhu; Jirun, Peng; Zhongtian, Jin; Shishi, Qiao; Zhuqingqing, Cui; Lei, Gong; Kim, Jin W

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world. The only serological marker widely used for the diagnosis of HCC is alpha-fetoprotein (AFP). Despite that AFP is widely used for the diagnosis of HCC, it has a limit as a serological marker due to its low sensitivity and specificity. The human cervical cancer proto-oncogene 1 (HCCR-1) was previously reported as a new biomarker for HCC. To further evaluate the HCCR-1 as a biomarker for HCC, we conducted the prospective cohort study. We evaluated the significance of simultaneous measurement of 2 tumor markers in the diagnosis of HCC in China, Japan and Korea. Two markers for HCC, AFP and HCCR-1, were measured in the sera obtained from 1,338 patients at the time of initial diagnosis of HCC. Of the 1338 HCC patients, 616 (46%) and 686 (51.3%) were sero-positive for AFP and HCCR-1, respectively. The positive rate for HCC was increased up to 74.1% in combined use of AFP and HCCR-1. Many cases (54%) for AFP-negative HCC were positive for HCCR-1 and vice versa. More importantly, the diagnostic rate for small HCC (< 2 cm) was significantly improved in the combined analysis of AFP and HCCR-1 to 56.9% although it was only 40.1% and 23.4% in the single analysis of HCCR-1 and AFP, respectively. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP.

  16. A Convenient and Efficient Method to Enrich and Maintain Highly Proliferative Human Fetal Liver Stem Cells.

    PubMed

    Guo, Xuan; Wang, Shu; Dou, Ya-ling; Guo, Xiang-fei; Chen, Zhao-li; Wang, Xin-wei; Shen, Zhi-qiang; Qiu, Zhi-gang; Jin, Min; Li, Jun-wen

    2015-06-01

    Pluripotent human hepatic stem cells have broad research and clinical applications, which are, however, restricted by both limited resources and technical difficulties with respect to isolation of stem cells from the adult or fetal liver. In this study, we developed a convenient and efficient method involving a two-step in situ collagenase perfusion, gravity sedimentation, and Percoll density gradient centrifugation to enrich and maintain highly proliferative human fetal liver stem cells (hFLSCs). Using this method, the isolated hFLSCs entered into the exponential growth phase within 10 days and maintained sufficient proliferative activity to permit subculture for at least 20 passages without differentiation. Immunocytochemistry, immunofluorescence, and flow cytometry results showed that these cells expressed stem cell markers, such as c-kit, CD44, epithelial cell adhesion molecule (EpCAM), oval cell marker-6 (OV-6), epithelial marker cytokeratin 18 (CK18), biliary ductal marker CK19, and alpha-fetoprotein (AFP). Gene expression analysis showed that these cells had stable mRNA expression of c-Kit, EpCAM, neural cell adhesion molecule (NCAM), CK19, CK18, AFP, and claudin 3 (CLDN-3) throughout each passage while maintaining low levels of ALB, but with complete absence of cytochrome P450 3A4 (C3A4), phosphoenolpyruvate carboxykinase (PEPCK), telomeric repeat binding factor (TRF), and connexin 26 (CX26) expression. When grown in appropriate medium, these isolated liver stem cells could differentiate into hepatocytes, cholangiocytes, osteoblasts, adipocytes, or endothelial cells. Thus, we have demonstrated a more economical and efficient method to isolate hFLSCs than magnetic-activated cell sorting (MACS). This novel approach may provide an excellent tool to isolate highly proliferative hFLSCs for tissue engineering and regenerative therapies.

  17. Effects of AFP gene silencing on Survivin mRNA expression inhibition in HepG2 cells.

    PubMed

    Fang, Z L; Fang, N; Han, X N; Huang, G; Fu, X J; Xie, G S; Wang, N R; Xiong, J P

    2015-04-10

    We investigated the effects of alpha-fetoprotein (AFP) gene silencing on Survivin expression in HepG2 cells. Small interfering RNA technology was used to downregulate AFP expression in HepG2 cells. An enzyme-linked immunosorbent assay was used to measure AFP concentration in the supernatant before and after transfection. An MTT assay was used to detect cell proliferation activity before and after transfection. We performed flow cytometric analysis to detect the cell apoptosis rate, and reverse transcription-polymerase chain reaction to detect Survivin mRNA levels before and after transfection. Forty-eight hours after transfection, AFP concentration in the supernatant of the experimental group significantly decreased, hepatocellular carcinoma cell growth was inhibited by 43.1%, and the apoptosis rate increased by 24.3%. Survivin mRNA expression was reduced by 78.0% in HepG2 cells. These indicators in the control group and in the blank group did not change significantly. Silencing of AFP expression in HepG2 cells can effectively inhibit the growth of hepatoma cells and promote apoptosis, which may be useful for reducing intracellular Survivin mRNA levels.

  18. 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.

  19. Tumor-targeted gene therapy using Adv-AFP-HRPC/IAA prodrug system suppresses growth of hepatoma xenografted in mice.

    PubMed

    Dai, M; Liu, J; Chen, D-E; Rao, Y; Tang, Z-J; Ho, W-Z; Dong, C-Y

    2012-02-01

    Clinical efficacy of current therapies for hepatocellular carcinoma (HCC) treatment is limited. Indole-3-acetic acid (IAA) is non-toxic for mammalian cells. Oxidative decarboxylation of IAA by horseradish peroxidase (HRP) leads to toxic effects of IAA. The purpose of this study was to investigate the effects of a novel gene-targeted enzyme prodrug therapy with IAA on hepatoma growth in vitro and in vivo mouse hepatoma models. We generated a plasmid using adenovirus to express HRP isoenzyme C (HRPC) with the HCC marker, alpha-fetoprotein (AFP), as the promoter (pAdv-AFP-HRPC). Hepatocellular cells were infected with pAdv-AFP-HRPC and treated with IAA. Cell death was detected using MTT assay. Hepatoma xenografts were developed in mice by injection of mouse hepatoma cells. The size and weight of tumors and organs were evaluated. Cell death in tumors was assessed using hematoxylin and eosin-stained tissue sections. HRPC expression in tissues was detected using Reverse Transcriptase-Polymerase Chain Reaction. IAA stimulated death of hepatocellular cells infected with pAdv-AFP-HRPC, in a dose- and time-dependent manner, but not in control cells. Growth of hepatoma xenografts, including the size and weight, was inhibited in mice treated with pAdv-AFP-HRPC and IAA, compared with that in control group. pAdv-AFP-HRPC/IAA treatment induced cell death in hepatoma xenografts in mice. HRPC gene expressed only in hepatoma, but not in other normal organs of mice. pAdv-AFP-HRPC/IAA treatment did not cause any side effects on normal organs. These findings suggest that pAdv-AFP-HRPC/IAA enzyme/prodrug system may serve as a strategy for HCC therapy.

  20. 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.

  1. Simple and robust diagnosis of early, small and AFP-negative primary hepatic carcinomas: an integrative approach of serum fluorescence and conventional blood tests

    PubMed Central

    Wang, Ting; Zhang, Kun-He; Hu, Piao-Ping; Huang, Zeng-Yong; Zhang, Pan; Wan, Qin-Si; Huang, De-Qiang; Lv, Nong-Hua

    2016-01-01

    The diagnosis of early, small and alpha-fetoprotein (AFP)-negative primary hepatic carcinomas (PHCs) remains a significant challenge. We developed a simple and robust approach to noninvasively detect these PHCs. A rapid, high-throughput and single-tube method was firstly developed to measure serum autofluorescence and cell-free DNA (cfDNA)-related fluorescence using a real-time PCR system, and both types of serum fluorescence were measured and routine laboratory data were collected in 1229 subjects, including 353 PHC patients, 331 liver cirrhosis (LC) patients, 213 chronic hepatitis (CH) patients and 332 normal controls (NC). The results showed that fluorescence indicators of PHC differed from those of NC, CH and LC to various extents, and all of them were not associated with age, gender, or AFP level. The logistic regression models established with the fluorescence indicators alone and combined with AFP, hepatic function tests and blood cell analyses were valuable for distinguishing early, small, AFP-negative and all PHC from LC, CH, NC and all non-PHC, with areas under the receiver operating characteristic curves 0.857–0.993 and diagnostic accuracies 80.2–97.7%. Conclusively, serum autofluorescence and cfDNA-related fluorescence are able to be rapidly and simultaneously measured by our simple method and valuable for diagnosing early, small and AFP-negative PHCs, especially integrating with AFP and conventional blood tests. PMID:27590520

  2. Simple and robust diagnosis of early, small and AFP-negative primary hepatic carcinomas: an integrative approach of serum fluorescence and conventional blood tests.

    PubMed

    Wang, Ting; Zhang, Kun-He; Hu, Piao-Ping; Huang, Zeng-Yong; Zhang, Pan; Wan, Qin-Si; Huang, De-Qiang; Lv, Nong-Hua

    2016-09-27

    The diagnosis of early, small and alpha-fetoprotein (AFP)-negative primary hepatic carcinomas (PHCs) remains a significant challenge. We developed a simple and robust approach to noninvasively detect these PHCs. A rapid, high-throughput and single-tube method was firstly developed to measure serum autofluorescence and cell-free DNA (cfDNA)-related fluorescence using a real-time PCR system, and both types of serum fluorescence were measured and routine laboratory data were collected in 1229 subjects, including 353 PHC patients, 331 liver cirrhosis (LC) patients, 213 chronic hepatitis (CH) patients and 332 normal controls (NC). The results showed that fluorescence indicators of PHC differed from those of NC, CH and LC to various extents, and all of them were not associated with age, gender, or AFP level. The logistic regression models established with the fluorescence indicators alone and combined with AFP, hepatic function tests and blood cell analyses were valuable for distinguishing early, small, AFP-negative and all PHC from LC, CH, NC and all non-PHC, with areas under the receiver operating characteristic curves 0.857-0.993 and diagnostic accuracies 80.2-97.7%. Conclusively, serum autofluorescence and cfDNA-related fluorescence are able to be rapidly and simultaneously measured by our simple method and valuable for diagnosing early, small and AFP-negative PHCs, especially integrating with AFP and conventional blood tests.

  3. Icaritin inhibits the expression of alpha-fetoprotein in hepatitis B virus-infected hepatoma cell lines through post-transcriptional regulation

    PubMed Central

    Zhang, Chao; Li, Hui; Jiang, Wei; Zhang, Xiaowei; Li, Gang

    2016-01-01

    Although it has showed that icaritin can apparently suppress growth of HCC by reducing the level of AFP, the intrinsic mechanism remains unclear. In this study, we explored the possible mechanism of miRNAs on post-transcriptional regulation of AFP gene, as well as the effects of HBV infection and icaritin in hepatoma cells. The results showed that miR-620, miR-1236 and miR-1270 could bind target sites in the range of 9–18 nt and 131–151 nt downstream of the stop codon in the AFP mRNA 3′-UTR to suppress the expression of AFP. Mutation of these target sites could reverse the effects of these miRNAs. Icaritin (10 μM) might reduce the stability and translational activity of AFP mRNA by increasing the expression levels of these mentioned miRNAs. HBV infection resulted in apparent decreases of these miRNAs and, consequently, increased AFP expression. The results indicated that miR-620, miR-1236 and miR-1270 are critical factors in the post-transcriptional regulation of AFP. Icaritin can counteract the effect of HBV. These findings will contribute to full understanding of the regulatory mechanism of AFP expression in hepatoma cells. And also it revealed a synergistic mechanism of HBV infection and elevation of AFP in the pathogenesis of HCC, as well as the potential clinical significance of icaritin on the therapy of HCC induced by HBV. PMID:27835879

  4. Birth Defects Diagnosis

    MedlinePlus

    ... quad screen tests the levels of 4 proteins AFP (alpha-fetoprotein), hCG, estriol, and inhibin-A. Generally, ... of the proteins for which an amniocentesis tests. AFP AFP stands for alpha-fetoprotein, a protein the ...

  5. Hepatoma cell-specific ganciclovir-mediated toxicity of a lentivirally transduced HSV-TkEGFP fusion protein gene placed under the control of rat alpha-fetoprotein gene regulatory sequences.

    PubMed

    Uch, Rathviro; Gérolami, René; Faivre, Jamila; Hardwigsen, Jean; Mathieu, Sylvie; Mannoni, Patrice; Bagnis, Claude

    2003-09-01

    Suicide gene therapy combining herpes simplex virus thymidine kinase gene transfer and ganciclovir administration can be envisioned as a powerful therapeutical approach in the treatment of hepatocellular carcinoma; however, safety issues regarding transgene expression in parenchyma cells have to be addressed. In this study, we constructed LATKW, a lentiviral vector expressing the HSV-TkEGFP gene placed under the control of the promoter elements that control the expression of the rat alpha-fetoprotein, and assayed its specific expression in vitro in hepatocarcinoma and nonhepatocarcinoma human cell lines, and in epidermal growth factor stimulated human primary hepatocytes. Using LATKW, a strong expression of the transgene was found in transduced hepatocarcinoma cells compared to a very low expression in nonhepatocarcinoma human cell lines, as assessed by Northern blot, RT-PCR, FACS analysis and ganciclovir-mediated toxicity assay, and no expression was found in lentivirally transduced normal human hepatocytes. Altogether, these results demonstrate the possibility to use a lentivirally transduced expression unit containing the rat alpha-fetoprotein promoter to restrict the HSV-TK-mediated induced GCV sensitivity to human hepatocarcinoma cells.

  6. Sandwich-type electrochemical immunosensor for the detection of AFP based on Pd octahedral and APTES-M-CeO₂-GS as signal labels.

    PubMed

    Wei, Yicheng; Li, Yan; Li, Na; Zhang, Yong; Yan, Tao; Ma, Hongmin; Wei, Qin

    2016-05-15

    In the present work, an ultrasensitive sandwich-type electrochemical immunosensor based on a novel signal amplification strategy was designed for quantitative detection of alpha fetoprotein (AFP). Au nanoparticles with biocompatibility were electrodeposited on the surface of glassy carbon electrode (GCE) which can effectively capture and immobilize primary anti-AFP (Ab1) to significantly amplify the electrochemical signal. Graphene Oxide and CeO2 mesoporous nanocomposite functionalized by the 3-aminopropyltriethoxysilane supported Pd octahedral nanoparticles (Pd/APTES-M-CeO2-GS) were utilized as labels of detection anti-AFP (Ab2). Pd octahedral nanoparticles presented good catalytic activity towards the reduction of H2O2. Due to the large specific surface area and good adsorption properties of APTES-CeO2-GS nanocomposite, large amount of Pd octahedral nanoparticles could be immobilized, which could amplify the electrochemical signal and improve the sensitivity of the immunosensor. Under optimal conditions, the immunosensor exhibited wide linear range from 0.1 pg/mL to 50 ng/mL with a low detection limit of 0.033 pg/mL (S/N=3) for AFP detection. In addition, high sensitivity, excellent selectivity, good reproducibility and stability were obtained for the immunosensor, which has a promising application for quantitative detection of other tumor markers in clinical diagnosis.

  7. Metastatic pancreatic acinar cell carcinoma in a younger male with marked AFP production: A potential pitfall on fine needle aspiration biopsy.

    PubMed

    Valente, Kari; Yacoub, George; Cappellari, James O; Parks, Graham

    2017-02-01

    A 30-year-old male presented to his doctor with complaints of abdominal pain and was found to have retroperitoneal as well as multiple hepatic masses. A serum alpha-fetoprotein (AFP) level was significantly elevated (17,373 ng mL(-1) ), raising suspicions for a metastatic germ cell tumor. Fine needle aspiration biopsy of the pancreatic lesion revealed atypical epithelioid cells with round nuclei, large prominent nucleoli, and granular cytoplasm. The morphologic differential diagnosis included pancreatic neoplasm, metastatic germ cell tumor, other metastatic carcinoma, and melanoma. An extensive panel of immunohistochemical stains confirmed the diagnosis of acinar cell carcinoma. The diagnosis of acinar cell carcinoma could be confounded by the markedly increased AFP level, particularly in the setting of a retroperitoneal mass in a younger male. The increased AFP level in the setting of an acinar cell tumor is a potential pitfall to correct diagnosis by cytology. As the treatment for these two entities differs considerably, acute awareness of the phenomenon is important. We present a case of pancreatic ACC with an increased AFP level diagnosed on a cytology specimen. Diagn. Cytopathol. 2017;45:133-136. © 2016 Wiley Periodicals, Inc.

  8. Photoelectrochemical detection of alpha-fetoprotein based on ZnO inverse opals structure electrodes modified by Ag2S nanoparticles.

    PubMed

    Jiang, Yandong; Liu, Dali; Yang, Yudan; Xu, Ru; Zhang, Tianxiang; Sheng, Kuang; Song, Hongwei

    2016-12-06

    In this work, a new photoelectrochemical biosensor based on Ag2S nanoparticles (NPs) modified macroporous ZnO inverse opals structure (IOs) was developed for sensitive and rapid detection of alpha fetal protein (AFP). Small size and uniformly dispersed Ag2S NPs were prepared using the Successive Ionic Layer Adsorption And Reaction (SILAR) method, which were adsorbed on ZnO IOs surface and frame work as matrix for immobilization of AFP. The composite structure of ZnO/Ag2S expanded the scope of light absorption to long wavelength, which can make full use of the light energy. Meanwhile, an effective matching of energy levels between the conduction bands of Ag2S and ZnO are beneficial to the photo-generated electrons transfer. The biosensors based on FTO (fluorine-doped tinoxide) ZnO/Ag2S electrode showed enough sensitivity and a wide linear range from 0.05 ng/mL to 200 ng/mL with a low detection limit of 8 pg/mL for the detection of AFP. It also exhibited high reproducibility, specificity and stability. The proposed method was potentially attractive for achieving excellent photoelectrochemical biosensor for detection of other proteins.

  9. Photoelectrochemical detection of alpha-fetoprotein based on ZnO inverse opals structure electrodes modified by Ag2S nanoparticles

    PubMed Central

    Jiang, Yandong; Liu, Dali; Yang, Yudan; Xu, Ru; Zhang, Tianxiang; Sheng, Kuang; Song, Hongwei

    2016-01-01

    In this work, a new photoelectrochemical biosensor based on Ag2S nanoparticles (NPs) modified macroporous ZnO inverse opals structure (IOs) was developed for sensitive and rapid detection of alpha fetal protein (AFP). Small size and uniformly dispersed Ag2S NPs were prepared using the Successive Ionic Layer Adsorption And Reaction (SILAR) method, which were adsorbed on ZnO IOs surface and frame work as matrix for immobilization of AFP. The composite structure of ZnO/Ag2S expanded the scope of light absorption to long wavelength, which can make full use of the light energy. Meanwhile, an effective matching of energy levels between the conduction bands of Ag2S and ZnO are beneficial to the photo-generated electrons transfer. The biosensors based on FTO (fluorine-doped tinoxide) ZnO/Ag2S electrode showed enough sensitivity and a wide linear range from 0.05 ng/mL to 200 ng/mL with a low detection limit of 8 pg/mL for the detection of AFP. It also exhibited high reproducibility, specificity and stability. The proposed method was potentially attractive for achieving excellent photoelectrochemical biosensor for detection of other proteins. PMID:27922086

  10. Hepatocyte growth factor incorporated chitosan nanoparticles augment the differentiation of stem cell into hepatocytes for the recovery of liver cirrhosis in mice

    PubMed Central

    2011-01-01

    Background Short half-life and low levels of growth factors in the niche of injured microenvironment necessitates the exogenous and sustainable delivery of growth factors along with stem cells to augment the regeneration of injured tissues. Methods Here, recombinant human hepatocyte growth factor (HGF) was incorporated into chitosan nanoparticles (CNP) by ionic gelation method and studied for its morphological and physiological characteristics. Cirrhotic mice received either hematopoietic stem cells (HSC) or mesenchymal stemcells (MSC) with or without HGF incorporated chitosan nanoparticles (HGF-CNP) and saline as control. Biochemical, histological, immunostaining and gene expression assays were carried out using serum and liver tissue samples. One way analysis of variance was used for statics application Results Serum levels of selected liver protein and enzymes were significantly increased in the combination of MSC and HGF-CNP (MSC+HGF-CNP) treated group. Immunopositive staining for albumin (Alb) and cytokeratin 18 (CK18), and reverse transcription-polymerase chain reaction (RT-PCR) for Alb, alpha fetoprotein (AFP), CK18, cytokeratin 19 (CK19) ascertained that MSC-HGF-CNP treatment could be an effective combination to repopulate liver parenchymal cells in the liver cirrhosis. Zymogram and western blotting for matrix metalloproteinases 2 and 9 (MMP2 and MMP9) revealed that MMP2 actively involved in the fibrolysis of cirrhotic tissue. Immunostaining for alpha smooth muscle actin (αSMA) and type I collagen showed decreased expression in the MSC+HGF-CNP treatment. These results indicated that HGF-CNP enhanced the differentiation of stem cells into hepatocytes and supported the reversal of fibrolysis of extracellular matrix (ECM). Conclusion Bone marrow stem cells were isolated, characterized and transplanted in mice model. Biodegradable biopolymeric nanoparticles were prepared with the pleotrophic protein molecule and it worked well for the differentiation of stem

  11. What Is Testicular Cancer?

    MedlinePlus

    ... of a tumor marker protein called alpha-fetoprotein (AFP), as well as human chorionic gonadotropin (HCG). Yolk ... of tumor almost always increases blood levels of AFP (alpha-fetoprotein). Choriocarcinoma: This is a very rare ...

  12. Combination of miR-125b and miR-27a enhances sensitivity and specificity of AFP-based diagnosis of hepatocellular carcinoma.

    PubMed

    Zuo, Duo; Chen, Liwei; Liu, Xiaoqian; Wang, Xia; Xi, Qing; Luo, Yi; Zhang, Ning; Guo, Hua

    2016-05-01

    Non-invasive biomarkers of early-stage hepatocellular carcinoma (HCC) could offer immense benefits. Currently available tumor markers for HCC are of not much clinical relevance. In this study, we investigated the potential for using a panel of serum microRNAs (miRNAs) as novel tumor markers in conjunction with serum alpha-fetoprotein (AFP) for diagnosis of HCC. Serum expression of four miRNAs was assessed in 150 subjects (90 cases of HCC and 60 cases without cancer) by quantitative real-time polymerase chain reaction (qRT-PCR). Logistic regression analysis was performed to assess the potential use of miRNAs for detection of HCC. Receiver operating characteristic curves were used to evaluate diagnostic accuracy. A panel of serum miRNAs (miR-125b, miR-223, miR-27a, and miR-26a) used in conjunction with AFP helped differentiate HCC patients from those in the non-cancer group after adjusting for age and gender, with the area under the curve of 0.870. In addition, the use of miR-125b/miR-27a panel differentiated HBV-related early-stage HCC with a high sensitivity (80.0 %) and specificity (87.2 %) in AFP-negative (-) subjects. A combination of serum miR-125b, miR-223, miR-27a, and miR-26a as a second-line tests could help detect HCC in AFP (-) subjects. The panel of miR-125b/miR-27a/AFP had a higher sensitivity and specificity for diagnosis of early-stage HCC as compared to that of a single marker.

  13. Role of antifeeding prophage (Afp) protein Afp16 in terminating the length of the Afp tailocin and stabilizing its sheath.

    PubMed

    Rybakova, Daria; Radjainia, Mazdak; Turner, Adrian; Sen, Anindito; Mitra, Alok K; Hurst, Mark R H

    2013-08-01

    The Serratia entomophila antifeeding prophage Afp, forms a phage-tail-like particle that acts on the New Zealand grass grub, Costelytra zealandica with a 3-day LD50 of approximately 500 Afp particles per larva. Genes (afp1-18) encoding components of Afp were expressed and their products purified allowing morphological assessment of the products by transmission electron microscopy (TEM). Expression of afp1-15 resulted in the formation of a non-sheathed structure termed the tube-baseplate complex or TBC, composed of an irregular-length tube attached to a baseplate with associated tail fibres. Expression of afp1-16 produced mature, normal-length Afp particles, whereas coexpression of afp16 with afp1-15 in trans resulted in the formation of aberrant Afp particles of variable lengths. A C-terminally truncated Afp16 mutant resulted in a phenotype intermediate between mature Afp and TBC. The addition of purified Afp16 to Afp unravelled by acidic treatment resulted in the formation of shorter tubes when specimen pH was adjusted to 7 than those formed in the absence of Afp16. Analysis of TEM images of purified Afp16 revealed a hexameric ring-like structure similar to that formed by gp3 of phage T4 and gpU of phage λ. Our results suggest that Afp16 terminates tube elongation and is involved in sheath formation.

  14. Afp14 is involved in regulating the length of Anti-feeding prophage (Afp).

    PubMed

    Rybakova, Daria; Schramm, Peter; Mitra, Alok K; Hurst, Mark R H

    2015-05-01

    The anti-feeding prophage (Afp), a phage-tail-like particle that causes cessation of feeding in the New Zealand grass grub, Costelytra zealandica, is encoded by 18 open reading frames (afp1-18). C-terminal truncations of afp14 resulted in shortened Afp particles, suggesting that Afp14 is involved in Afp length determination. We constructed an Afp assembly system (afp1-18), wherein Afp14 was truncated after the N-terminal 88 residues. This construct, when expressed in trans in Escherichia coli expressing a N-terminal 98-amino acid Afp14 construct, yielded fully assembled Afp but no assembled Afp was detected in the case of a N-terminal 96-amino acid Afp14 construct. These results suggested that the 98 N-terminal, amino acid residues of Afp14 is crucial for the initiation of Afp assembly via baseplate formation. Trans-based expression of wild-type afp14 resulted in Afp particles of varying lengths, all of which were shorter than the wild-type Afp particle. On the other hand, similar expression of Afp14 harboring a C-terminal extension (KLLEH(6)) resulted in elongated Afp particles. This information, combined with bioinformatics data, allowed us to propose a model delineating the mechanism and role of Afp14 in the maturation of the Afp particle.

  15. 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

  16. 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.

  17. Genetics Home Reference: ataxia with oculomotor apraxia

    MedlinePlus

    ... high amounts of a protein called alpha-fetoprotein (AFP) in their blood. (An increase in the level ... tissue. The effect of abnormally high levels of AFP or CPK in people with ataxia with oculomotor ...

  18. General Information about Testicular Cancer

    MedlinePlus

    ... are used to detect testicular cancer: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). Tumor marker ... places in the body, and blood levels of AFP, β-hCG, and LDH). Type of cancer. Size ...

  19. How Is Testicular Cancer Diagnosed?

    MedlinePlus

    ... proteins called tumor markers , such as alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). When these tumor ... that there is a testicular tumor. Rises in AFP or HCG can also help doctors tell which ...

  20. 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.

  1. 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.

  2. 21 CFR 866.6030 - AFP-L3% immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false AFP-L3% immunological test system. 866.6030... Systems § 866.6030 AFP-L3% immunological test system. (a) Identification. An AFP-L3% immunological test... measure, by immunochemical techniques, AFP and AFP-L3 subfraction in human serum. The device is...

  3. Malignant teratoma of the mediastinum

    MedlinePlus

    ... following tests help diagnose the tumor: Chest x-ray CT scans of the chest, abdomen, and pelvis Blood tests to check beta-HCG, alpha fetoprotein (AFP), and lactate dehydrogenase (LDH) levels Mediastinoscopy ...

  4. Readout and trigger for the AFP detector at ATLAS experiment

    NASA Astrophysics Data System (ADS)

    Kocian, M.

    2017-01-01

    AFP, the ATLAS Forward Proton consists of silicon detectors at 205 m and 217 m on each side of ATLAS. In 2016 two detectors in one side were installed. The FEI4 chips are read at 160 Mbps over the optical fibers. The DAQ system uses a FPGA board with Artix chip and a mezzanine card with RCE data processing module based on a Zynq chip with ARM processor running ArchLinux. In this contribution we give an overview of the AFP detector with the commissioning steps taken to integrate with the ATLAS TDAQ. Furthermore first performance results are presented.

  5. 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.

  6. [Preliminary investigation on acute flaccid paralysis (AFP) cases in Jinan area].

    PubMed

    Xu, A; Li, L; Zhao, S

    1994-06-01

    Eighty AFP cases under 12 years old from 6 hospitals in Jinan were investigated. Among them, there were 17 (21.25%) cases with poliomyelitis (POLIO), 40 (50.00%) cases with Guillian-Barre syndrome (GBS) and 23 (28.75%) cases with other AFP diseases. Most AFP cases occurred from May to October and no significant seasonal difference was found for each kind of AFP cases (P > 0.05), but the average age for POLIO cases (1.55 +/- 1.24) was significantly lower than that for non-POLIO AFP cases (3.76 +/- 2.58) (P < 0.01). The reporting rate from hospitals to each level of epidemic prevention station (EPS) for POLIO, GBS and other AFP cases were 100%, 12.50% and 43.75%, respectively (P < 0.01). Sixty-five AFP cases occurred in 6 prefectures around Jinan city. The average incidence rate (per 100,000) for total AFP, non-POLIO AFP and GBS cases among children under 12 years old were 1.11, 0.89 and 0.53, respectively. The results are helpful to estimate the incidence of AFP cases among children in north provinces of China and also indicate that the POLIO surveillance system in Shandong Province at the present is not sensitive enough, so the AFP cases reporting work of hospitals and the surveillance at each level of EPS should be enhanced.

  7. Derivation of three clones from human embryonic stem cell lines by FACS sorting and their characterization.

    PubMed

    Sidhu, Kuldip S; Tuch, Bernard E

    2006-02-01

    Here we describe the first report of three human embryonic stem cell (hESC) clones, hES 3.1, 3.2, and 3.3, derived from the parent line hES3 by sorting of single-cell preparations by flow cytometry. The viability of single-cell preparations before and after cell sorting remained >98%. The hESC were selected by size gating and forward-angle light scatter and were dispersed directly as single cell/ well into 96-well plates containing human fetal fibroblasts as feeder layers. Single stem cell dispersion into 96-well plates was confirmed by using cells from a hES3 line that constitutively expressed green fluorescence protein (eGFP) under similar conditions of flow cytometry. Three clones were obtained from the parent line hES3 -- hES3.1, 3.2, and 3.3 -- and they have been in continuous culture for more than 1 year. The cloning efficiency was less than <0.5%. These hESC clones show normal stem cell characteristics, such as undifferentiated growth, high nucleocytoplasmic ratio, the same karyotype as that of the parent line (46 XX), stem cell surface markers (i.e., SSEA3, SSEA4, OCT4, TRA-1-60, and TRA-1-81), and gene expression for pluripotency (Oct-4 and nanog). They all formed embryoid bodies in suspension cultures, and after seeding in culture plates they showed pluripotency in vitro by forming cell lineages derived from all three germ layers as indicated by expression of the ectodermal marker nestin, the mesodermal marker renin, and the endodermal markers alpha-fetoprotein and GATA6. All clones showed normal expression of alkaline phosphatase activity, a marker of in vitro pluripotency. When hESC clones (1-2 x 10(6) total) were injected into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice under the kidney capsule, all formed teratomas within 6-8 weeks. Analysis of the stem cell surface marker TRA-1-160 by flow cytometry showed nonsignificant (p < 0.05) differences between the clones and the parent line. The clones also differed in their expression

  8. Surveillance of acute flaccid paralysis (AFP) in Lombardy, Northern Italy, from 1997 to 2011 in the context of the national AFP surveillance system

    PubMed Central

    Pellegrinelli, Laura; Primache, Valeria; Fiore, Lucia; Amato, Concetta; Fiore, Stefano; Bubba, Laura; Pariani, Elena; Amendola, Antonella; Barbi, Maria; Binda, Sandro

    2014-01-01

    An Acute Flaccid Paralysis (AFP) surveillance system was set up in Lombardy (Northern Italy) in 1997 in the framework of the national AFP surveillance system, as part of the polio eradication initiative by the World Health Organization (WHO). This surveillance system can now be used to detect Poliovirus (PV) reintroductions from endemic countries. This study aimed at describing the results of the AFP surveillance in Lombardy, from 1997 to 2011. Overall, 131 AFP cases in Lombardy were reported with a mean annual incidence rate of 0.7/100 000 children <15 years of age (range: 0.3/100 000–1.1/100 000). The sensitivity of the surveillance system was optimal from 2001–2003. The monthly distribution of AFP cases was typical with peaks in November, in January, and in March. The major clinical diagnoses associated with AFP were Guillain-Barré Syndrome (GBS, 40%) and encephalomyelitis/myelitis (13%). According to the virological results, no poliomyelitis cases were caused by wild PV infections, but two Vaccine-Associated Paralytic Paralysis (VAPP) cases were reported in 1997 when the Sabin oral polio vaccine (OPV) was still being administered in Italy. Since a surveillance system is deemed sensitive if at least one case of AFP per 100,000 children <15 years of age is detected each year, our surveillance system needs some improvement and must be maintained until global poliovirus eradication will be declared. PMID:25483546

  9. Surveillance of acute flaccid paralysis (AFP) in Lombardy, Northern Italy, from 1997 to 2011 in the context of the national AFP surveillance system.

    PubMed

    Pellegrinelli, Laura; Primache, Valeria; Fiore, Lucia; Amato, Concetta; Fiore, Stefano; Bubba, Laura; Pariani, Elena; Amendola, Antonella; Barbi, Maria; Binda, Sandro

    2015-01-01

    An Acute Flaccid Paralysis (AFP) surveillance system was set up in Lombardy (Northern Italy) in 1997 in the framework of the national AFP surveillance system, as part of the polio eradication initiative by the World Health Organization (WHO). This surveillance system can now be used to detect Poliovirus (PV) reintroductions from endemic countries. This study aimed at describing the results of the AFP surveillance in Lombardy, from 1997 to 2011.   Overall, 131 AFP cases in Lombardy were reported with a mean annual incidence rate of 0.7/100 000 children <15 years of age (range: 0.3/100 000-1.1/100 000). The sensitivity of the surveillance system was optimal from 2001-2003. The monthly distribution of AFP cases was typical with peaks in November, in January, and in March. The major clinical diagnoses associated with AFP were Guillain-Barré Syndrome (GBS, 40%) and encephalomyelitis/myelitis (13%). According to the virological results, no poliomyelitis cases were caused by wild PV infections, but two Vaccine-Associated Paralytic Paralysis (VAPP) cases were reported in 1997 when the Sabin oral polio vaccine (OPV) was still being administered in Italy. Since a surveillance system is deemed sensitive if at least one case of AFP per 100,000 children <15 years of age is detected each year, our surveillance system needs some improvement and must be maintained until global poliovirus eradication will be declared.

  10. Surveillance of acute flaccid paralysis (AFP) in Lombardy, Northern Italy, from 1997 to 2011 in the context of the national AFP surveillance system.

    PubMed

    Pellegrinelli, Laura; Primache, Valeria; Fiore, Lucia; Amato, Concetta; Fiore, Stefano; Bubba, Laura; Pariani, Elena; Amendola, Antonella; Barbi, Maria; Binda, Sandro

    2014-08-28

    An Acute Flaccid Paralysis (AFP) surveillance system was set up in Lombardy (Northern Italy) in 1997 in the framework of the national AFP surveillance system, as part of the polio eradication initiative by the World Health Organization (WHO). This surveillance system can now be used to detect Poliovirus (PV) reintroductions from endemic countries. This study aimed at describing the results of the AFP surveillance in Lombardy, from 1997 to 2011.   Overall, 131 AFP cases in Lombardy were reported with a mean annual incidence rate of 0.7/100 000 children<15 years of age (range: 0.3/100 000-1.1/100 000). The sensitivity of the surveillance system was optimal from 2001-2003. The monthly distribution of AFP cases was typical with peaks in November, in January, and in March. The major clinical diagnoses associated with AFP were Guillain-Barré Syndrome (GBS, 40%) and encephalomyelitis/myelitis (13%). According to the virological results, no poliomyelitis cases were caused by wild PV infections, but two Vaccine-Associated Paralytic Paralysis (VAPP) cases were reported in 1997 when the Sabin oral polio vaccine (OPV) was still being administered in Italy. Since a surveillance system is deemed sensitive if at least one case of AFP per 100,000 children<15 years of age is detected each year, our surveillance system needs some improvement and must be maintained until global poliovirus eradication will be declared.

  11. 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.

  12. [Assessment of AFP in amniotic fluid: comparison of three automated techniques].

    PubMed

    Leguy, Marie-Clémence; Tavares, Silvina Dos Reis; Tsatsaris, Vassili; Lewin, Fanny; Clauser, Eric; Guibourdenche, Jean

    2011-01-01

    Ultrasound scanning is useful to detect neural tube defect (NTD) but scarcely distinguished between closed NTD and open NTD, which had very different prognosis. An amniotic fluid punction is thus mandatory to search for an increase in alpha foeto protein (AFP) levels and for the presence of acetylcholinesterase which identified open NTD. However, AFP levels fluctuate both with the gestational age and the assay used. Our aim was to establish normative values for AFP in amniotic fluid in the second half of pregnancy using three different immunoassays and to improve their clinical relevance. Amniotic fluid punctions were performed on 527 patients from 9 week of gestation (WG) to 37 WG either for maternal age, Trisomy 21 screening, increase in nucal translucency (control group, n = 527) or for suspicion of neural tube defect or abdominal defect (n = 5). AFP was measured using the immunoassay developed for serum AFP on the Access 2 system, the Immulite 2000 and the Advia Centaur. Results were expressed in ng/ml, multiple of the median (MoM) and percentiles. AFP decrease by 1.5 fold between 9 and 19 WG. When NTD was suspected, an increase in anmniotic AFP was observed (from 2.5 MoM to 9.3 MoM) confirming an open NTD. In conclusion, the assay developed on those 3 automates is suitable for the measurement of AFP in amniotic fluid.

  13. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma.

    PubMed

    Sauzay, Chloé; Petit, Alexandra; Bourgeois, Anne-Marie; Barbare, Jean-Claude; Chauffert, Bruno; Galmiche, Antoine; Houessinon, Aline

    2016-12-01

    Alpha-foetoprotein (AFP), one of the first protein tumour markers discovered, is widely used today in clinical practice. Its application for the screening and diagnosis of hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour, is a matter of extensive debate. In addition to the studies focused on the role of the AFP in the diagnosis of HCC, in recent years AFP has been used to guide the therapeutic choice in HCC and monitor the treatment. Here, we summarize the latest studies that show the interest of AFP quantification in determining the suitability of liver transplantation or to follow-up on patients receiving the targeted treatment sorafenib. We also highlight the recent studies showing the active role of AFP in tumour progression, and the new modes of regulation of this tumour marker. Among these is the regulation of AFP through tumour proteostasis and the Unfolded Protein Response (UPR). We discuss the implications of this new knowledge in the therapeutic context, in terms of interpreting serum levels of AFP, and the new perspectives offered by AFP for the study of tumour proteostasis.

  14. C-reactive protein is a biomarker of AFP-negative HBV-related hepatocellular carcinoma.

    PubMed

    She, Sha; Xiang, Yi; Yang, Min; Ding, Xiangchun; Liu, Xiaoyan; Ma, Lina; Liu, Qing; Liu, Bin; Lu, Zhenhui; Li, Shiying; Liu, Yi; Ran, Xiaoping; Xu, Xiaoming; Hu, Huaidong; Hu, Peng; Zhang, Dazhi; Ren, Hong; Yang, Yixuan

    2015-08-01

    Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide and is associated with the high rates of morbidity and mortality. α-fetoprotein (AFP) is common used in diagnosis of HCC; however, a growing body of research is questioning the diagnostic power of AFP. There is, therefore, an urgent need to develop additional novel non-invasive techniques for the early diagnosis of HCC, particularly for patients with AFP-negative [AFP(-)] HCC. Accordingly, in the present study, we employed iTRAQ-based mass spectro-metry to analyze the plasma proteins of subjects with AFP(-) HBV-related HCC, AFP(+) HBV-related HCC and non-malignant cirrhosis. We identified 14 aberrantly expressed proteins specific to the HCC patients, including 10 upregulated and 4 downregulated proteins. We verified C-reactive protein (CRP) overexpression by ELISA and immunohistochemical staining of clinical samples. Per ROC curve analyses, CRP was positive in 73.3% of patients with HBV-related HCC, and CRP overexpression had significant diagnostic power for AFP(-) HBV-related HCC. Furthermore, we found that silencing CRP caused a >2-fold decease in HBV replication. Additionally, we determined that this reduction in HBV replication involved the interferon-signaling pathway. However, silencing CRP also promoted HCC invasion and migration in vitro. In conclusion, we demonstrated that CRP can serve as a diagnostic biomarker for AFP(-) HBV-related HCC.

  15. Module production of the one-arm AFP 3D pixel tracker

    NASA Astrophysics Data System (ADS)

    Grinstein, S.; Cavallaro, E.; Chmeissani, M.; Dorholt, O.; Förster, F.; Lange, J.; Lopez Paz, I.; Manna, M.; Pellegrini, G.; Quirion, D.; Rijssenbeek, M.; Rohne, O.; Stugu, B.

    2017-01-01

    The ATLAS Forward Proton (AFP) detector is designed to identify events in which one or two protons emerge intact from the LHC collisions. AFP will consist of a tracking detector, to measure the momentum of the protons, and a time of flight system to reduce the background from multiple proton-proton interactions. Following an extensive qualification period, 3D silicon pixel sensors were selected for the AFP tracker. The sensors were produced at CNM (Barcelona) during 2014. The tracker module assembly and quality control was performed at IFAE during 2015. The assembly of the first AFP arm and the following installation in the LHC tunnel took place in February 2016. This paper reviews the fabrication process of the AFP tracker focusing on the pixel modules.

  16. [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.

  17. The GALAD scoring algorithm based on AFP, AFP-L3, and DCP significantly improves detection of BCLC early stage hepatocellular carcinoma.

    PubMed

    Best, J; Bilgi, H; Heider, D; Schotten, C; Manka, P; Bedreli, S; Gorray, M; Ertle, J; van Grunsven, L A; Dechêne, A

    2016-12-01

    Background: Hepatocellular carcinoma (HCC) is one of the leading causes of death in cirrhotic patients worldwide. The detection rate for early stage HCC remains low despite screening programs. Thus, the majority of HCC cases are detected at advanced tumor stages with limited treatment options. To facilitate earlier diagnosis, this study aims to validate the added benefit of the combination of AFP, the novel biomarkers AFP-L3, DCP, and an associated novel diagnostic algorithm called GALAD. Material and methods: Between 2007 and 2008 and from 2010 to 2012, 285 patients newly diagnosed with HCC and 402 control patients suffering from chronic liver disease were enrolled. AFP, AFP-L3, and DCP were measured using the µTASWako i30 automated immunoanalyzer. The diagnostic performance of biomarkers was measured as single parameters and in a logistic regression model. Furthermore, a diagnostic algorithm (GALAD) based on gender, age, and the biomarkers mentioned above was validated. Results: AFP, AFP-L3, and DCP showed comparable sensitivities and specifities for HCC detection. The combination of all biomarkers had the highest sensitivity with decreased specificity. In contrast, utilization of the biomarker-based GALAD score resulted in a superior specificity of 93.3 % and sensitivity of 85.6 %. In the scenario of BCLC 0/A stage HCC, the GALAD algorithm provided the highest overall AUROC with 0.9242, which was superior to any other marker combination. Conclusions: We could demonstrate in our cohort the superior detection of early stage HCC with the combined use of the respective biomarkers and in particular GALAD even in AFP-negative tumors.

  18. Epigenetic regulation of GATA4 expression by histone modification in AFP-producing gastric adenocarcinoma.

    PubMed

    Yamamura, Nobuhisa; Kishimoto, Takashi

    2012-08-01

    AFP-producing adenocarcinoma is a variant of adenocarcinoma with high malignancy. Production of AFP suggests enteroblastic or hepatoid differentiation of cancer cells. GATA4 is a key molecule involved in the prenatal development of the stomach and liver. GATA4 is epigenetically silenced by hypermethylation of primer region in many types of cancers including gastric cancer. The aim of this study is to investigate the expression and epigenetic regulation of GATA4 in AFP-producing adenocarcinoma. Immunohistochemical analysis revealed that GATA4 was positive in 3/8 cases of AFP-producing gastric adenocarcinomas and in 28/30 cases of common type adenocarcinomas. Epigenetic modification of GATA4 promoter region was investigated with 3 AFP-producing and 4 common-type gastric cancer cell lines. GATA4 mRNA was detected in 1/3 of AFP-producing and 2/4 of common-type gastric cancer cell lines by RT-PCR. Methylation-specific PCR revealed no GATA4 methylation in any of the AFP-producing gastric cancers, whereas methylation was consistent with GATA4 expression in the common-type gastric cancers. Chromatin immunoprecipitation assay for AFP-producing gastric cancers revealed that histones H3 and H4 were hypoacetylated in the GATA4-negative cells, while they were hyperacetylated in the GATA4-positive cells. Treatment with trichostain A, an inhibitor for histone deacetylase, induced acetylation of histones H3 and H4, and tri-methylation of lysine 4 of histone H3, which was associated with the active transcription of GATA4 in GATA4-negative AFP-producing cells. These results indicated that histone deacetylation is a silencing mechanism for GATA4 expression in AFP-producing gastric cancer cells. Differences between AFP-producing gastric cancer and common-type gastric cancer in terms of the mechanism of GATA4 regulation may be reflected in the phenotypic deviation of AFP-producing gastric cancer from common-type gastric cancer.

  19. 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

  20. Solution structure of an antifreeze protein CfAFP-501 from Choristoneura fumiferana.

    PubMed

    Li, Congmin; Guo, Xianrong; Jia, Zongchao; Xia, Bin; Jin, Changwen

    2005-07-01

    Antifreeze proteins (AFPs) are widely employed by various organisms as part of their overwintering survival strategy. AFPs have the unique ability to suppress the freezing point of aqueous solution and inhibit ice recrystallization through binding to the ice seed crystals and restricting their growth. The solution structure of CfAFP-501 from spruce budworm has been determined by NMR spectroscopy. Our result demonstrates that CfAFP-501 retains its rigid and highly regular structure in solution. Overall, the solution structure is similar to the crystal structure except the N- and C-terminal regions. NMR spin-relaxation experiments further indicate the overall rigidity of the protein and identify a collection of residues with greater flexibilities. Furthermore, Pro91 shows a cis conformation in solution instead of the trans conformation determined in the crystal structure.

  1. Evaluation of AFP surveillance indicators in polio-free Ghana, 2009–2013

    PubMed Central

    2014-01-01

    Background Ghana recorded the last case of indigenous wild poliovirus in 1999 but suffered two more outbreaks in 2003 and 2008. Following the World Health Organization (WHO) guidelines, transmission was interrupted through high routine immunisation coverage with live-attenuated oral polio vaccine (OPV), effective acute flaccid paralysis (AFP) surveillance and supplementary immunisation activities (SIA). This article describes the results of a five-year surveillance of AFP in polio-free Ghana, evaluate the surveillance indicators and identify areas that need improvement. Methods We investigated 1345 cases of AFP from children aged less than 15 years reported to the Disease Surveillance Department from January 2009 to December 2013. Data on demographic characteristics, vaccination history, clinical presentation and virological investigation on stool specimens collected during investigation were analysed. Results Of the specimens analysed, 56% were from males and 76.3% were from children less than 5 years of age. Twenty-four percent of the children received up to 3 doses of OPV, 57% received at least 4 doses while the status of 19% was unknown. Core AFP surveillance indicators were partly met for non-polio AFP rate while the WHO target for stool adequacy and timeliness was exceeded over the period of study. All the cases were classified virologically, however no wild polio was found. Sixty-day follow-up was conducted for 56.3% of cases and 8.6% cases classified as compactible with polio. Conclusion Both laboratory and epidemiological surveillance for AFP were efficient and many WHO targets were met. However, due to the risk of poliovirus importation prior to global eradication, longterm surveillance is required to provide a high degree of confidence in prevention of poliovirus infection in Ghana. Thus, efforts should be made to strengthen regional performance and to follow–up on all AFP cases in order to establish proper diagnoses for the causes of the AFP leading

  2. Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells.

    PubMed

    Ferreira, Lino S; Gerecht, Sharon; Fuller, Jason; Shieh, Hester F; Vunjak-Novakovic, Gordana; Langer, Robert

    2007-06-01

    We propose a new methodology to enhance the vascular differentiation of human embryonic stem cells (hESCs) by encapsulation in a bioactive hydrogel. hESCs were encapsulated in a dextran-based hydrogel with or without immobilized regulatory factors: a tethered RGD peptide and microencapsulated VEGF(165). The fraction of cells expressing vascular endothelial growth factor (VEGF) receptor KDR/Flk-1, a vascular marker, increased up to 20-fold, as compared to spontaneously differentiated embryoid bodies (EBs). The percentage of encapsulated cells in hydrogels with regulatory factors expressing ectodermal markers including nestin or endodermal markers including alpha-fetoprotein decreased 2- or 3-fold, respectively, as compared to EBs. When the cells were removed from these networks and cultured in media conditions conducive for further vascular differentiation, the number of vascular cells was higher than the number obtained through EBs, using the same media conditions. Functionalized dextran-based hydrogels could thus enable derivation of vascular cells in large quantities, particularly endothelial cells, for potential application in tissue engineering and regenerative medicine.

  3. Targeting Gene-Viro-Therapy with AFP driving Apoptin gene shows potent antitumor effect in hepatocarcinoma

    PubMed Central

    2012-01-01

    Background Gene therapy and viral therapy are used for cancer therapy for many years, but the results are less than satisfactory. Our aim was to construct a new recombinant adenovirus which is more efficient to kill hepatocarcinoma cells but more safe to normal cells. Methods By using the Cancer Targeting Gene-Viro-Therapy strategy, Apoptin, a promising cancer therapeutic gene was inserted into the double-regulated oncolytic adenovirus AD55 in which E1A gene was driven by alpha fetoprotein promoter along with a 55 kDa deletion in E1B gene to form AD55-Apoptin. The anti-tumor effects and safety were examined by western blotting, virus yield assay, real time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, Hoechst33342 staining, Fluorescence-activated cell sorting, xenograft tumor model, Immunohistochemical assay, liver function analysis and Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay. Results The recombinant virus AD55-Apoptin has more significant antitumor effect for hepatocelluar carcinoma cell lines (in vitro) than that of AD55 and even ONYX-015 but no or little impair on normal cell lines. Furthermore, it also shows an obvious in vivo antitumor effect on the Huh-7 liver carcinoma xenograft in nude mice with bigger beginning tumor volume till about 425 mm3 but has no any damage on the function of liver. The induction of apoptosis is involved in AD55-Apoptin induced antitumor effects. Conclusion The AD55-Apoptin can be a potential anti-hepatoma agent with remarkable antitumor efficacy as well as higher safety in cancer targeting gene-viro-therapy system. PMID:22321574

  4. 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.

  5. Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo.

    PubMed

    Liu, Yang; Butterfield, Lisa H; Fu, Xiaohui; Song, Zhenshun; Zhang, Xiaoping; Lu, Chongde; Ding, Guanghui; Wu, Mengchao

    2011-07-01

    α-fetoprotein (AFP), a tumor-associated antigen for hepatocellular carcinoma (HCC), is an established biomarker for HCC. In this study, we created a lentivirus expressing the AFP antigen and investigated the anti-tumor activity of AFP-specific CD8+ T cells, with and without CD4+ T cells, which were activated by either AFP peptide-pulsed or Lenti-AFP-engineered Dendritic cells (DCs) in vitro and in vivo. AFP-specific T cells could efficiently kill HepG2 HCC cells, and produced IL-2, IFN-γ, TNF-α, perforin and granzyme B, with minimal production of IL-10 (a negative regulator of T cell activation). Both strategies activated AFP-specific T cells, but the lentiviral strategy was superior by several measures. Data also support an impact of CD4+ T cells in supporting anti-tumor activity. In vivo studies in a xenograft HCC tumor model also showed that AFP-specific T cells could markedly suppress HCC tumor formation and morbidity in tumor-bearing nude mice, as well as regulate serum levels of related cytokines and anti-tumor molecules. In parallel with human in vitro T cell cultures, the in vivo model demonstrated superior anti-tumor effects and Th1-skewing with Lenti-AFP-DCs. This study supports the superiority of a full-length antigen lentivirus-based DCs vaccine strategy over peptides, and provides new insight into the design of DCs-based vaccines.

  6. 99MTC Alpha-Fetoprotein: A Novel, Specific Agent for the Detection of Human Breast Cancer.

    DTIC Science & Technology

    1999-07-01

    produce recombinant virus . Virus was plaque- purified, then screened for the incorporation of the Domain III coding sequence into the viral genome...by PCR; Polymerase Chain Reaction) and for the ability of recombinant virus to produce secreted protein (Western Blot). Recombinant baculovirus...quantity of vi- rus. Protein was then produced in large batches by infection of SF9 cells with recombinant virus . The medium containing the secreted

  7. Hereditary persistence of alpha-fetoprotein mimicking testicular cancer in a patient with acute epididymitis.

    PubMed

    Abt, Dominik; Meier, Mark; Markart, Patrick; Schmid, Hans-Peter

    2011-11-01

    Only a few cases of hereditary persistence of α-fetoprotein (HPAFP) have been published. This report presents an association between HPAFP and inflammatory testis disease, to the authors' knowledge, for the first time. HPAFP was diagnosed in a 41-year-old patient with acute epididymitis after exclusion of malignancies and benign diseases.

  8. The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans

    PubMed Central

    Thevissen, Karin; de Mello Tavares, Patricia; Xu, Deming; Blankenship, Jill; Vandenbosch, Davy; Idkowiak-Baldys, Jolanta; Govaert, Gilmer; Bink, Anna; Rozental, Sonia; de Groot, Piet W.J.; Davis, Talya R.; Kumamoto, Carol A.; Vargas, Gabriele; Nimrichter, Leonardo; Coenye, Tom; Mitchell, Aaron; Roemer, Terry; Hannun, Yusuf A.; Cammue, Bruno P.A.

    2012-01-01

    Summary The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal glucosylceramides and induces apoptosis in Candida albicans. To further unravel the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a library of 2,868 heterozygous C. albicans deletion mutants and identified 30 RsAFP2-hypersensitive mutants. The most prominent group of RsAFP2 tolerance genes was involved in cell wall integrity and hyphal growth/septin ring formation. Consistent with these genetic data, we demonstrated that RsAFP2 interacts with the cell wall of C. albicans, which also contains glucosylceramides, and activates the cell wall integrity pathway. Moreover, we found that RsAFP2 induces mislocalization of septins and blocks the yeast-to-hypha transition in C. albicans. Increased ceramide levels have previously been shown to result in apoptosis and septin mislocalization. Therefore, ceramide levels in C. albicans membranes were analyzed following RsAFP2 treatment and, as expected, increased accumulation of phytoC24-ceramides in membranes of RsAFP2-treated C. albicans cells was detected. This is the first report on the interaction of a plant defensin with glucosylceramides in the fungal cell wall, causing cell wall stress, and on the effects of a defensin on septin localization and ceramide accumulation. PMID:22384976

  9. The Immune System as a New Possible Cell Target for AFP 464 in a Spontaneous Mammary Cancer Mouse Model.

    PubMed

    Callero, Mariana A; Rodriguez, Cristina E; Sólimo, Aldana; Bal de Kier Joffé, Elisa; Loaiza Perez, Andrea I

    2017-02-16

    Aminoflavone (AFP 464, NSC 710464), an antitumor agent which recently entered phase II clinical trials, acts against estrogen-positive breast cancer (ER +). AFP 464, which has a unique mechanism of action by activating aryl hydrocarbon receptor (AhR) signaling pathway, decreased tumor size and growth rate in the estrogen dependent, Tamoxifen-sensitive spontaneous M05 mouse model. Considering that AhR has recently emerged as a physiological regulator of the innate and adaptive immune responses, we investigated whether AFP 464 modulates the immune response in our mouse model. Studies on the effect of AFP 464 on the immune system were carried in BALB/c mice bearing M05 semi-differentiated mammary adenocarcinomas that express estrogen and progesterone receptors. Splenic cells and tumor inflammatory infiltrates were studied by cytometric analyses. The modulation of splenocytes cytotoxic activity by AFP 464 was also evaluated. We further investigated the effects of AFP 464 on peritoneal macrophages by evaluating metalloproteinase, arginase and iNOS activities. We found that AFP 464 increased splenic cytotoxic activity, diminished the number of systemic and local Treg lymphocytes and MDSCs, and induced a M1 phenotype in peritoneal macrophages of M05 tumor bearing mice. Therefore, we conclude that AFP 464 modulates immune response which collaborates with its anti-tumor activity. Our results place the immune system as a novel target for this anti-cancer agent to strengthen the rationale for its inclusion in breast cancer treatment regimens. This article is protected by copyright. All rights reserved.

  10. [Epidemiological analysis on morbidity of acute flaccid paralysis (AFP) among children under 15 years old in 14 provinces of China].

    PubMed

    Zhang, X L; Wang, K A

    1995-12-01

    Five investigations through analysis of hospital records on morbidity of Acute Flaccid Paralysis (AFP) among children under 15 years old in 14 provinces of China have currently been conducted. In this paper, data from a series of studies published in journals or reported to meetings was combined and analyzed based on Meta-Analysis. Comparisons have been made between AFP, poliomyelitis, Guillian-Barre Syndrome (GBS) and non-polio AFP morbidities and their distributions by age, sex and month. The morbidity rates for these four categories were 1.41, 0.54, 0.55 and 1.05 per 10(5) respectively. An important conclusion drawn from of this study was that the criterion put forward by WHO, reported rate of non-polio AFP should reach over 1.0 per 10(5) among children under 15, can also be used as an indicator for sensitivity evaluation and monitoring of AFP surveillance system in China.

  11. Impact of the antifungal protein PgAFP from Penicillium chrysogenum on the protein profile in Aspergillus flavus.

    PubMed

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

    2015-10-01

    Antifungal proteins produced by molds are generally small, highly basic, and cysteine-rich. The best known effects of these proteins include morphological changes, metabolic inactivation, and membrane perturbation on sensitive fungi. Reactive oxygen species (ROS) generation leads to apoptosis, with G -protein playing a key role in transduction of cell death signals. The antifungal protein PgAFP from Penicillium chrysogenum inhibits growth of some toxigenic molds. Here we analyzed the effect of the antifungal protein PgAFP on the growth of Aspergillus flavus. For this, comparative proteomic analysis was used to identify the whole protein profile and protein change in abundance after PgAFP treatment. PgAFP provoked metabolic changes related to reduced energy metabolism, cell wall integrity alteration, and increased stress response due to higher levels of ROS. The observed changes in protein abundance, favoring a higher glutathione concentration as well as the increased abundance in heat shock proteins, do not seem to be enough to avoid necrosis. The decreased chitin deposition observed in PgAFP-treated A. flavus is attributed to a lower relative quantity of Rho1. The reduced relative abundance of a β subunit of G -protein seems to be the underlying reason for modulation of apoptosis in PgAFP-treated A. flavus hyphae. We propose Rho1 and G -protein subunit β CpcB to be the main factors in the mode of action of PgAFP in A. flavus. Additionally, enzymes essential for the biosynthesis of aflatoxin were no longer detectable in A. flavus hyphae at 24 h, following treatment with PgAFP. This presents a promising effect of PgAFP, which may prevent A. flavus from producing mycotoxins. However, the impact of PgAFP on actual aflatoxin production requires further study.

  12. The effects of antifreeze peptide III (AFP) and insulin transferrin selenium (ITS) on cryopreservation of chimpanzee (Pan troglodytes) spermatozoa.

    PubMed

    Younis, A I; Rooks, B; Khan, S; Gould, K G

    1998-01-01

    We investigated the effects of antifreeze peptides (AFP) and insulin transferrin selenium (ITS) on the motility and membrane integrity of chimpanzee (Pan troglodytes) spermatozoa after chilling (0-5 degrees C) and thawing. The effects of three thawing procedures, in the presence or absence of AFP and ITS, on sperm motility and on the status of the plasma membrane and acrosome were also examined. During chilling, AFP and ITS seem mildly cytotoxic, as the progressive motility and velocity (curvilinear and straight line) declined significantly at AFP concentrations of 1, 10, and 100 microg/ml and at ITS concentrations of 1 and 10 microg/ml. However, at a concentration of 100 microg/ml, ITS was able to protect sperm during short-term hypothermic storage. Addition of AFP or ITS at 100 microg/ml to test egg yolk-glycerol extender during freezing significantly (P < 0.05) increased postthaw motility, plasma membrane integrity, and acrosome integrity. The mean (+/-SE) motility recovery rate increased from 28.9 +/- 3.9%, for the untreated control, to 59.2 +/- 5.8% and 67.8 +/- 7.4%, for ITS and AFP, respectively. The effects of the thawing procedure were influenced by the presence of AFP during the freezing cycle. An improved motility recovery rate of 67 +/- 4.2% was obtained when chimpanzee sperm frozen in test egg yolk-glycerol extender supplemented with AFP were thawed rapidly at 37 degrees C, compared to 47 +/- 5.2% and 44 +/- 8.2% for slow (23 degrees C) and ultrarapid (75 degrees C) thawing, respectively. The motility recovery after thawing of ITS-treated semen at 23 degrees C, 37 degrees C, or 75 degrees C was not significantly different. Semen frozen without AFP or ITS and thawed at 75 degrees C was seriously (P < 0.05) damaged. This study provides evidence that AFP- or ITS-supplemented semen extender improves postthaw sperm motility in the chimpanzee.

  13. 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...

  14. Neutron structure of type-III antifreeze protein allows the reconstruction of AFP-ice interface.

    PubMed

    Howard, Eduardo I; Blakeley, Matthew P; Haertlein, Michael; Petit-Haertlein, Isabelle; Mitschler, Andre; Fisher, Stuart J; Cousido-Siah, Alexandra; Salvay, Andrés G; Popov, Alexandre; Muller-Dieckmann, Christoph; Petrova, Tatiana; Podjarny, Alberto

    2011-01-01

    Antifreeze proteins (AFPs) inhibit ice growth at sub-zero temperatures. The prototypical type-III AFPs have been extensively studied, notably by X-ray crystallography, solid-state and solution NMR, and mutagenesis, leading to the identification of a compound ice-binding surface (IBS) composed of two adjacent ice-binding sections, each which binds to particular lattice planes of ice crystals, poisoning their growth. This surface, including many hydrophobic and some hydrophilic residues, has been extensively used to model the interaction of AFP with ice. Experimentally observed water molecules facing the IBS have been used in an attempt to validate these models. However, these trials have been hindered by the limited capability of X-ray crystallography to reliably identify all water molecules of the hydration layer. Due to the strong diffraction signal from both the oxygen and deuterium atoms, neutron diffraction provides a more effective way to determine the water molecule positions (as D(2) O). Here we report the successful structure determination at 293 K of fully perdeuterated type-III AFP by joint X-ray and neutron diffraction providing a very detailed description of the protein and its solvent structure. X-ray data were collected to a resolution of 1.05 Å, and neutron Laue data to a resolution of 1.85 Å with a "radically small" crystal volume of 0.13 mm(3). The identification of a tetrahedral water cluster in nuclear scattering density maps has allowed the reconstruction of the IBS-bound ice crystal primary prismatic face. Analysis of the interactions between the IBS and the bound ice crystal primary prismatic face indicates the role of the hydrophobic residues, which are found to bind inside the holes of the ice surface, thus explaining the specificity of AFPs for ice versus water.

  15. Real-Time Quantification of AFP mRNA to Assess Hematogenous Dissemination After Transarterial Chemoembolization of Hepatocellular Carcinoma

    PubMed Central

    Gross-Goupil, Marine; Saffroy, Raphaël; Azoulay, Daniel; Precetti, Sophie; Emile, Jean-François; Delvart, Valérie; Tindilière, Fréderic; Laurent, Alexis; Bellin, Marie-France; Bismuth, Henri; Debuire, Brigitte; Lemoine, Antoinette

    2003-01-01

    Objective: To determine whether the number of hepatocytes containing AFP mRNA shed into the bloodstream during transarterial chemoembolization (TAE) affects the incidence and pattern of recurrence of hepatocellular carcinoma (HCC). Patients and Methods: We developed a Taqman procedure to quantify AFP mRNA prospectively in 52 consecutive patients before and after TAE. Results are expressed in hepatocytes /mL. Results: Thirteen of the patients (24.5%) were positive for AFP mRNA (42 ± 19 hepatocytes/mL) before TAE and 13 (24.5%) (80 ± 32 hepatocytes/mL) after TAE; the difference was not significant. The presence of AFP mRNA in the bloodstream before TAE was associated with larger nodules (85.2 ± 73.8 mm versus 34.8 ± 26.1 mm; P = 0.006). Six of the patients were excluded from the analysis because they underwent curative surgery or were lost to follow-up. The circulating levels of AFP mRNA released in the 46 remaining patients after TAE did not affect metastasis-free survival. A significant number of extrahepatic metastases were found in patients exhibiting at least 1 AFP mRNA-positive blood sample either before or after TAE. However, the TAE procedure did not increase the risk of extrahepatic recurrences. Conclusion: Cells containing AFP mRNA are inconsistently released into the circulation during TAE. The amount of these cells released does not affect the recurrence of HCC. PMID:12894018

  16. [An investigation on acute flaccid paralysis (AFP) cases in some provinces with high risk of poliomyelitis of China].

    PubMed

    Wang, Z; Yang, B P; Li, H F

    1995-04-01

    In the mid Jun, 1994, a study team organized by MOPH investigated AFP cases in 10 provinces with high prevalence of poliomyelitis (polio). Twenty prefectures and ten counties were selected randomly from each of 10 provinces and relevant prefectures. The team identified 681 AFP cases under 15 years old from 45 hospitals at prefecture level and 13 hospitals at country level based on hospital records from cases occurred during 1991-1994. AFP, Polio, Non-polio AFP and GBS (Guillian-Barre Syndrome) cases aged from 0-14 years scattered around 101 counties (cities) among target population and their average incidences by year were 1.04, 0.48, 0.57 and 0.31 (per 10(5) respectively. Noticingly, the incidence of polio had reduced significantly since 1991, and its proportion among AFP was also reducing from first place yearly since 1991. In addition, over 95% of the polio cases were concentrated in the 4 year olds which indicated that the target population for surveillance and prevention should mainly be focusing on 0-4 year olds. As the incidence of non-polio AFP has been used as a current sensitive index of surveillance system, we noticed that the incidence rates had been significantly different from various regions. According to the analytic data, we recommend that "Rate of non-polio AFP in children 0-14 years of age greater than 1/10(5)" might be a better and more sensitive index for surveillance program in China.

  17. Comparison of oval cells induced in rat liver by feeding N-2-fluorenylacetamide in a choline-devoid diet and bile duct cells induced by feeding 4,4'-diaminodiphenylmethane.

    PubMed

    Sell, S

    1983-04-01

    Oval cells and duct-like structures produced in the livers of rats fed N-2-fluorenylacetamide in a choline-devoid diet differ from bile ducts produced after feeding 4,4'-diaminodiphenylmethane. Rapid elevations of serum alpha-fetoprotein (AFP) occur after feeding N-2-fluorenylacetamide in a choline-devoid diet; no elevations of AFP are seen during 4,4'-diaminodiphenylmethane feeding. The duct-like structures associated with oval cells frequently contain AFP and albumin and are faintly delineated by laminin, whereas normal bile ducts and ducts induced by 4,4'-diaminodiphenylmethane do not contain AFP or albumin and are delineated by an intensely staining layer of laminin. Zones of oval cell proliferation label intensely for fibronectin, whereas zones of bile duct proliferation label much less intensely. It is concluded that the "tubuloform degeneration" seen after carcinogen exposure does not necessarily represent differentiation to true bile duct structures and that oval cells may neither derive from nor differentiate into bile ducts. Oval cells have characteristics more like fetal hepatocytes than ductular cells and may represent a "stem cell"-like population with potential for loss of growth control and malignant transformation.

  18. iAFP-Ense: An Ensemble Classifier for Identifying Antifreeze Protein by Incorporating Grey Model and PSSM into PseAAC.

    PubMed

    Xiao, Xuan; Hui, Mengjuan; Liu, Zi

    2016-12-01

    Antifreeze proteins (AFPs), known as thermal hysteresis proteins, are ice-binding proteins. AFPs have been found in many fields such as in vertebrates, invertebrates, plants, bacteria, and fungi. Although the function of AFPs is common, the sequences and structures of them show a high degree of diversity. AFPs can be adsorbed in ice crystal surface and inhibit the growth of ice crystals in solution. However, the interaction between AFPs and ice crystal is not completely known for human beings. It is vitally significant to propose an automated means as a high-throughput tool to timely identify the AFPs. Analyzing physicochemical characteristics of AFPs sequences is very significant to understand the ice-protein interaction. In this manuscript, a predictor called "iAFP-Ense" was developed. The operation engine to run the AFPs prediction is an ensemble classifier formed by a voting system to fuse eleven different random forest classifiers based on feature extraction. We also compare our predictor with the AFP-PseAAC via the tenfold cross-validation on the same benchmark dataset. The comparison with the existing methods indicates the new predictor is very promising, meaning that many important key features which are deeply hidden in complicated protein sequences. The predictor used in this article is freely available at http://www.jci-bioinfo.cn/iAFP-Ense .

  19. Expression of insect (Microdera puntipennis dzungarica) antifreeze protein MpAFP149 confers the cold tolerance to transgenic tobacco.

    PubMed

    Wang, Yan; Qiu, Liming; Dai, Chunying; Wang, Jing; Luo, Jianmin; Zhang, Fuchun; Ma, Ji

    2008-08-01

    To elucidate the function of antifreeze protein from Microdera puntipennis dzhungarica for freezing stress tolerance in plant, the construct of MpAFP149 gene with the signal peptide sequence responsible for secreting the native MpAFP149 into the apoplast space under control of a cauliflower mosaic virus 35S promoter was introduced into tobacco by Agrobacterium tumefaciens-mediated transformation. The observation of immunogold localization by TEM (transmission electron microscope) showed that the heterologous MpAFP149 protein was mainly distributed on the cell wall in apoplast of the transgenic tobacco plant. T1 generation transgenic tobacco plants displayed a more frost resistant phenotype and kept the lower ion leakage ratio and MDA (malondialdehyde) content in the leaves compared with wild-type ones at -1 degrees C for 3 days. The results showed that MpAFP149 provided protection and conferred cold tolerance to transgenic tobacco plant during freezing stress.

  20. 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

  1. 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.

  2. Strand Burner Results of AFP-001 Propellant with Inert Coating for Temperature Compensation

    DTIC Science & Technology

    2015-10-01

    the model will include burning rate information on the coated propellants , ballistic simulator data, as well as chemical and morphological results...MD): Army Research Laboratory (US); Sept 2013. Report No.: ARL-TR-6578. 7. Miller M, Vanderhoff J. Burning phenomena of solid propellants . Aberdeen...ARL-MR-0907 ● OCT 2015 US Army Research Laboratory Strand Burner Results of AFP-001 Propellant with Inert Coating for Temperature

  3. 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.

  4. 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.

  5. Co-transfection of dendritic cells with AFP and IL-2 genes enhances the induction of tumor antigen-specific antitumor immunity.

    PubMed

    Yang, Jing-Yue; Li, Xiao; Gao, Li; Teng, Zeng-Hui; Liu, Wen-Chao

    2012-10-01

    Dendritic cells (DCs) are highly efficient, specialized antigen-presenting cells and DCs transfected with tumor-related antigens are regarded as promising vaccines in cancer immunotherapy. The aim of the present study was to investigate whether DCs co-transfected with the α-fetoprotein (AFP) and human interleukin-2 (IL-2) genes were able to induce stronger therapeutic antitumor immunity in transfected DCs. In this study, DCs from hepatocellular carcinoma (HCC) patients were co-transfected with the IL-2 gene and/or the AFP gene. The reverse transcription-PCR (RT-PCR) data revealed that the DCs transfected with the adenovirus AdAFP/IL-2 expressed AFP and IL-2. The DCs co-transfected with IL-2 and AFP (AFP/IL-2-DCs) enhanced the cytotoxicities of cytotoxic T lymphocytes (CTLs) and increased the production of IL-2 and interferon-γ significantly compared with their AFP-DC, green fluorescent protein (GFP)-DC, DC or phosphate-buffered saline (PBS) counterparts. In vivo data suggested that immunization with AFP-DCs enhances antigen-specific antitumor efficacy more potently than immunization with IL-2-DCs or AFP-DCs. These findings provide a potential strategy to improve the efficacy of DC-based tumor vaccines.

  6. Liver Rapid Reference Set Application: Kevin Qu-Quest (2011) — EDRN Public Portal

    Cancer.gov

    We propose to evaluate the performance of a novel serum biomarker panel for early detection of hepatocellular carcinoma (HCC). This panel is based on markers from the ubiquitin-proteasome system (UPS) in combination with the existing known HCC biomarkers, namely, alpha-fetoprotein (AFP), AFP-L3%, and des-y-carboxy prothrombin (DCP). To this end, we applied multivariate logistic regression analysis to optimize this biomarker algorithm tool.

  7. RAPID COMMUNICATION-- POLIO VACCINE COVERAGE IN THE ACUTE FLACCID PARALYSIS (AFP) CASES IN ROMANIA.

    PubMed

    Băicuş, Anda

    2015-01-01

    Poliovirus (PV), a member of the Enterovirus genus, is the etiological agent of poliomyelitis. A study carried out between 2013-2014 on 30 serum samples from acute flaccid paralysis (AFP) cases, showed a protective antibody level of 90% against poliovirus Sabin strains type 1 and type 2 and of 88% against type 3. No PV strains were isolated from 2009 to 2015 in Romania. Maintaining a high vaccine coverage level against polio is mandatory until global polio eradication, especially as the risk of polio importation remains elevated in Romania.

  8. Nested polymerase chain reaction technique for the detection of Gpc3 and Afp mRNA in liver cancer micrometastases.

    PubMed

    Luo, J; Yang, K; Wen, Y G

    2017-02-08

    The incidence of liver cancer has gradually risen to a high level in China, and tumor metastasis occurs via multiple pathways. Alpha fetal protein (AFP) is the main biomarker of liver cancer micrometastases. A recent study showed that glypican-3 (GPC3), which is abundant in hepatoma cells, has promising specificity and could be used to determine the presence of malignant cells. The nested polymerase chain reaction (PCR) technique is superior in experimental sensitivity. Using rat models of liver cancer in the current study, we utilized nested PCR to detect Gpc3 and Afp mRNA to determine their relationship with liver cancer micrometastases. The aim was to provide an experimental basis for clinical examination. We randomly assigned male Sprague-Dawley rats to sham and experimental groups. The experimental group constituted a liver cancer model induced by diethylnitrosamine, whereas the sham group was administered with an equivalent volume of normal saline. Gpc3 and Afp mRNA was detected using nested PCR. Analysis was performed to determine statistical significance. Compared with the sham group, the rates of occurrence of Gpc3 and Afp mRNA were significantly higher in the experimental group (P < 0.05). Compared with the total positive ratio of hepatoma cells examined by joint detection, the rates of occurrence of Gpc3 and Afp mRNA increased significantly in the four subgroups of the experimental group (P < 0.05). The use of nested PCR significantly improved sensitivity for the detection of Gpc3 and Afp mRNA in liver cancer micrometastases.

  9. The Doylestown Algorithm: A Test to Improve the Performance of AFP in the Detection of Hepatocellular Carcinoma.

    PubMed

    Wang, Mengjun; Devarajan, Karthik; Singal, Amit G; Marrero, Jorge A; Dai, Jianliang; Feng, Ziding; Rinaudo, Jo Ann S; Srivastava, Sudhir; Evans, Alison; Hann, Hie-Won; Lai, Yinzhi; Yang, Hushan; Block, Timothy M; Mehta, Anand

    2016-02-01

    Biomarkers for the early diagnosis of hepatocellular carcinoma (HCC) are needed to decrease mortality from this cancer. However, as new biomarkers have been slow to be brought to clinical practice, we have developed a diagnostic algorithm that utilizes commonly used clinical measurements in those at risk of developing HCC. Briefly, as α-fetoprotein (AFP) is routinely used, an algorithm that incorporated AFP values along with four other clinical factors was developed. Discovery analysis was performed on electronic data from patients who had liver disease (cirrhosis) alone or HCC in the background of cirrhosis. The discovery set consisted of 360 patients from two independent locations. A logistic regression algorithm was developed that incorporated log-transformed AFP values with age, gender, alkaline phosphatase, and alanine aminotransferase levels. We define this as the Doylestown algorithm. In the discovery set, the Doylestown algorithm improved the overall performance of AFP by 10%. In subsequent external validation in over 2,700 patients from three independent sites, the Doylestown algorithm improved detection of HCC as compared with AFP alone by 4% to 20%. In addition, at a fixed specificity of 95%, the Doylestown algorithm improved the detection of HCC as compared with AFP alone by 2% to 20%. In conclusion, the Doylestown algorithm consolidates clinical laboratory values, with age and gender, which are each individually associated with HCC risk, into a single value that can be used for HCC risk assessment. As such, it should be applicable and useful to the medical community that manages those at risk for developing HCC.

  10. Development of a highly sensitive glycan microarray for quantifying AFP-L3 for early prediction of hepatitis B virus-related hepatocellular carcinoma.

    PubMed

    Wu, Chen-Shiou; Lee, Teng-Yu; Chou, Ruey-Hwang; Yen, Chia-Jui; Huang, Wei-Chien; Wu, Chung-Yi; Yu, Yung-Luen

    2014-01-01

    The α-fetoprotein fraction L3 (AFP-L3), which is synthesized by malignant cells and incorporates a fucosylated oligosaccharide, has been investigated as a diagnostic and prognostic marker for hepatocellular carcinoma (HCC). Quantification of AFP-L3 by conventional enzyme-linked immunosorbent assay (ELISA) has not always produced reliable results for serum samples with low AFP, and thus we evaluated the clinical utility of quantifying AFP-L3 using a new and highly sensitive glycan microarray assay. Sera from 9 patients with chronic hepatitis B and 32 patients with hepatitis B virus (HBV)-related HCC were tested for AFP-L3 level using the glycan microarray. Additionally, we compared receiver operator characteristic curves for the ELISA and glycan microarray methods for determination of the AFP-L3: AFP-L1 ratio in patient samples. This ratio was calculated for 8 HCC patients who underwent transarterial embolization therapy pre- or post-treatment with AFP-L3. Glycan microarrays showed that the AFP-L3 ratio of HBV-related HCC patients was significantly higher than that measured for chronic hepatitis B patients. Overall parameters for estimating AFP-L3% in HCC samples were as follows: sensitivity, 53.13%; specificity, 88.89%; and area under the curve, 0.75. The elevated AFP-L3% in the 8 patients with HBV-related HCC was strongly associated with HCC progression. Following one month of transarterial embolization therapy, the relative mean AFP-L3% decreased significantly. In addition, we compared Fut8 gene expression between paired tumor and non-tumor tissues from 24 patients with HBV-related HCC. The Fut8 mRNA expression was significantly increased in tumorous tissues in these patients than that in non-tumor tissue controls. Higher expression of Fut8 mRNA in tumorous tissues in these patients was associated with poor differentiation than well and moderate differentiation. Our results describe a new glycan microarray for the sensitive and rapid quantification of

  11. 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…

  12. 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.

  13. Stem Cells

    MedlinePlus

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

  14. Enhanced succinic acid production under acidic conditions by introduction of glutamate decarboxylase system in E. coli AFP111.

    PubMed

    Wu, Mingke; Li, Xiaozhan; Guo, Shunfeng; Lemma, Wubliker Dessie; Zhang, Wenming; Ma, Jiangfeng; Jia, Honghua; Wu, Hao; Jiang, Min; Ouyang, Pingkai

    2017-04-01

    Biological synthesis of succinic acid at low pH values was favored since it not only decreased investment cost but also simplified downstream purification process. In this study, the feasibility of using glutamate decarboxylase system to improve succinic acid production of Escherichia coli AFP111, a succinate-producing candidate with mutations in pfl, ldhA, and ptsG, under acidic conditions was investigated. By overexpressing gadBC operon in AFP111, a recombinant named as BA201 (AFP111/pMD19T-gadBC) was constructed. Fermentation at pH 5.6 showed that 30 g L(-1) glucose was consumed and 26.58 g L(-1) succinic acid was produced by BA201, which was 1.22- and 1.32-fold higher than that by the control BA200 (AFP111/pMD19T) containing the empty vector. Analysis of intracellular enzymes activities and ATP concentrations revealed that the activities of key enzymes involved in glucose uptake and products synthesis and intracellular ATP levels were all increased after overexpression of gadBC which were benefit for cell metabolism under weak acidic conditions. To further improve the succinic acid titer by recombinant BA201 at pH 5.6, the extracellular glutamate concentration was optimized and the final succinic acid titer increased 20.4% to 32.01 g L(-1). Besides, the fermentation time was prolonged by repetitive fermentation and additional 15.78 g L(-1) succinic acid was produced by recovering cells into fresh medium. The results here demonstrated a potential strategy of overexpressing gadBC for increased succinic acid production of E. coli AFP111 under weak acidic conditions.

  15. Psc-AFP from Psoralea corylifolia L. overexpressed in Pichia pastoris increases antimicrobial activity and enhances disease resistance of transgenic tobacco.

    PubMed

    Luo, Xiu-Mei; Xie, Cheng-Jian; Wang, De; Wei, Yun-Min; Cai, Jie; Cheng, Shan-Shan; Yang, Xing -Yong; Sui, An -Ping

    2017-02-01

    Psc-AFP, isolated from the seeds of Psoralea corylifolia L., is an antimicrobial protein with trypsin inhibitor activity. Its encoding gene was cloned by 3'- rapid amplification of cDNA ends (RACE) combined with Y-shaped adaptor-dependent extension (YADE) method. The gene Psc-AFP encodes a protein of 203 amino acids with a deduced signal peptide of 24 residues. The growth inhibition effect exerted by the heterologously expressed Psc-AFP in Pichia pastoris revealed that the recombinant Psc-AFP inhibited mycelium growth of Aspergillus niger, Rhizoctonia solani, and Alternaria brassicae and conidial germination of Alternaria alternata. The recombinant Psc-AFP also showed protease inhibitor activity manifested by the inhibition of trypsin. The transgenic tobacco bioassays confirmed that overexpressing Psc-AFP significantly enhanced the disease resistance of tobacco and that some of the transgenic lines were almost fully tolerant to Ralstonia solanacearum and A. alternata, whereas no apparent alteration in plant growth and development was observed. Collectively, these results indicate that the recombinant Psc-AFP is an active antimicrobial protein, with protease inhibitor activity that can be successfully produced in the yeast and tobacco and, therefore, maybe a potential antimicrobial candidate for practical use.

  16. AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis.

    PubMed

    Jin, Junhua; Niu, Xiaojuan; Zou, Lihui; Li, Lin; Li, Shugang; Han, Jingli; Zhang, Peiying; Song, Jinghai; Xiao, Fei

    2016-08-01

    Circulating tumor cells (CTCs) quantification may be helpful for evaluating cancer dissemination, predicting prognosis and assessing therapeutic effectiveness and safety. In the present study, CTCs from blood samples of 72 patients with hepatocellular carcinoma (HCC) were enriched with anti-EpCAM nanoparticles. AFP mRNA level was detected by nested polymerase chain reaction (PCR) after enrichment of CTCs from HCC blood samples at 0, 3, 6, 9 and 12 months after hepatectomy, respectively. AFP mRNA expression in CTCs was positive in 43 patients (59.7%) and negative in 29 patients (40.3%) before hepatectomy. Among 43 patients with positive AFP mRNA expression in CTCs before hepatectomy, 10 and 11 were diagnosed as intrahepatic/extrahepatic metastasis before and after hepatectomy, respectively. In addition, these 21 patients with metastasis had persisting positive AFP mRNA of CTCs during the whole tested year. Specifically, 3 patients with AFP mRNA negative in CTCs before hepatectomy changed to be positive at 6 and 9 months, and 2 of them were diagnosed as metastasis 12 months after hepatectomy. We conclude that the positive AFP mRNA of CTCs can be a pivotal predictor for HCC metastasis before and after hepatectomy. The release of AFP expression from hepatocellular carcinoma cells into circulation must be a major source of HCC metastasis.

  17. Comparison of hepatic-like cell production from human embryonic stem cells and adult liver progenitor cells: CAR transduction activates a battery of detoxification genes.

    PubMed

    Funakoshi, Natalie; Duret, Cédric; Pascussi, Jean-Marc; Blanc, Pierre; Maurel, Patrick; Daujat-Chavanieu, Martine; Gerbal-Chaloin, Sabine

    2011-09-01

    In vitro production of human hepatocytes is of primary importance in basic research, pharmacotoxicology and biotherapy of liver diseases. We have developed a protocol of differentiation of human embryonic stem cells (ES) towards hepatocyte-like cells (ES-Hep). Using a set of human adult markers including CAAT/enhancer binding protein (C/EBPalpha), hepatocyte nuclear factor 4/7 ratio (HNF4alpha1/HNF4alpha7), cytochrome P450 7A1 (CYP7A1), CYP3A4 and constitutive androstane receptor (CAR), and fetal markers including alpha-fetoprotein, CYP3A7 and glutathione S-transferase P1, we analyzed the expression of a panel of 41 genes in ES-Hep comparatively with human adult primary hepatocytes, adult and fetal liver. The data revealed that after 21 days of differentiation, ES-Hep are representative of fetal hepatocytes at less than 20 weeks of gestation. The glucocorticoid receptor pathway was functional in ES-Hep. Extending protocols of differentiation to 4 weeks did not improve cell maturation. When compared with hepatocyte-like cells derived from adult liver non parenchymal epithelial (NPE) cells (NPE-Hep), ES-Hep expressed several adult and fetal liver makers at much greater levels (at least one order of magnitude), consistent with greater expression of liver-enriched transcription factors Forkhead box A2, C/EBPalpha, HNF4alpha and HNF6. It therefore seems that ES-Hep reach a better level of differentiation than NPE-Hep and that these cells use different lineage pathways towards the hepatic phenotype. Finally we showed that lentivirus-mediated expression of xenoreceptor CAR in ES-Hep induced the expression of several detoxification genes including CYP2B6, CYP2C9, CYP3A4, UDP-glycosyltransferase 1A1, solute carriers 21A6, as well as biotransformation of midazolam, a CYP3A4-specific substrate.

  18. Synthesis of cadmium, lead and copper alginate nanobeads as immunosensing probes for the detection of AFP, CEA and PSA.

    PubMed

    Wang, Zifeng; Liu, Na; Feng, Feng; Ma, Zhanfang

    2015-08-15

    A double-water-in-oil-emulsion procedure was designed to synthesize cadmium, lead and copper alginate nanobeads less than 200n m diameter under mild conditions. The cadmium, lead and copper alginate nanobeads can be activated to immobilize biomacromolecules and can directly produce distinctive electrochemical signals. Using the novel alginate nanobeads labeled with antibodies as electrochemical probes, a sandwich-type immunosensor was constructed using AFP, CEA and PSA as model analytes. This proposed immunosensor shows wide linear range with detection limits of 0.01, 0.0086 and 0.0075 ng mL(-1) for AFP, CEA and PSA, respectively. Analysis of clinical serum samples using this immunosensor was well consistent with the data determined by the enzyme-linked immunosorbent assay (ELISA). It suggested that the alginate nanobeads electrochemical probes could be generally extended to other multiple analytes detection.

  19. 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

    2009-08-06

    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.

  20. 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.

  1. Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ -MALDI-MS/MS.

    PubMed

    He, X; Wang, Y; Zhang, W; Li, H; Luo, R; Zhou, Y; Li, C; Liao, M; Huang, H; Lv, X; Xie, Z; He, M

    2013-09-20

    Hepatocellular carcinoma (HCC) is serious condition associated with a high morbidity and mortality. Therefore is an urgent need to develop novel noninvasive techniques for early diagnosis, particularly for patients with AFP-negative [AFP(-)] HCC. In this study, iTRAQ-MALDI-MS/MS was used to identify differentially expressed proteins in AFP(-) HBV-related HCC compared with non-cancerous hepatitis B virus (HBV) and healthy controls subjects.Serum was obtained from 18 patients with AFP(-) HBV-related HCC, 18 matched patients with HBV without HCC and 18 healthy control subjects. High abundance proteins were removed from serum and the differentially expressed proteins from the three groups were screened out using iTRAQ-MALDI-MS/MS. The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. A total of 24 expressed differential proteins associated with AFP(-) HBV-related HCC were screened out, 15 proteins were up-regulated and 9 down-regulated. The most common molecular function of the 24 differentially expressed proteins was enzyme inhibition. Interaction network of the 24 differentially expressed proteins showed that 14 proteins (C5, KNG1, FN1, LRG1, HRG, SERPINC1, CRP, APOB, SAA1, APCS, C4BPA, CFI, CFB and GSN) were central to the functional network. The expression levels of the GSN protein were down-regulated in AFP(-) HBV-related HCC subjects compared with healthy controls and the HBV group (p<0.01), consistent with the iTRAQ results.The 14 proteins from the serum of AFP(-) HBV-related HCC appeared at the fulcrum of the functional network and were differentially expressed compare to HBV and healthy controls suggesting a possible association with HCC progression. Keywords: HCC, AFP Negative, iTRAQ, GSN.

  2. Levels of CEA, CA153, CA199, CA724 and AFP in nipple discharge of breast cancer patients

    PubMed Central

    Zhao, Song; Mei, Yu; Wang, Yongmei; Zhu, Jiang; Zheng, Guixi; Ma, Rong

    2015-01-01

    The distinction between breast cancer and benign breast diseases with nipple discharge remains an important diagnostic challenge. The purpose of this study was to predict the potential usefulness of tumor markers in nipple discharge and to investigate the relationship of tumor markers and clinical characteristics with breast cancer.One hundred and eleven patients with nipple discharge received breast surgery from November 2013 to December 2014 were included in the study. We evaluated levels of five tumor markers (CEA, CA153, CA199, CA724 and AFP) prior to treatment. Patients were divided into two groups according to postoperative pathological results: 30 cases in breast cancer group and 81 cases in benign group. The relationships of clinical characteristics with breast cancer were investigated by multivariate analysis with a logistic regression model.It showed significant differences in levels of nipple discharge CEA (P < 0.001) and CA153 (P = 0.014), but not CA199 (P = 0.856), CA724 (P = 0.171), AFP (P = 0.834) among two groups. Logistic regression analysis demonstrated complaint, age, menopause, abnormal palpable mass, CEA and CA153 were associated with breast cancer. In summary, measurements of CA199, CA724 and AFP in nipple discharge are not of great clinical value. Detecting CEA and CA153 in nipple dischargecould potentially be used for the early detection of breast cancer with in high-risk populations. PMID:26885008

  3. Levels of CEA, CA153, CA199, CA724 and AFP in nipple discharge of breast cancer patients.

    PubMed

    Zhao, Song; Mei, Yu; Wang, Yongmei; Zhu, Jiang; Zheng, Guixi; Ma, Rong

    2015-01-01

    The distinction between breast cancer and benign breast diseases with nipple discharge remains an important diagnostic challenge. The purpose of this study was to predict the potential usefulness of tumor markers in nipple discharge and to investigate the relationship of tumor markers and clinical characteristics with breast cancer.One hundred and eleven patients with nipple discharge received breast surgery from November 2013 to December 2014 were included in the study. We evaluated levels of five tumor markers (CEA, CA153, CA199, CA724 and AFP) prior to treatment. Patients were divided into two groups according to postoperative pathological results: 30 cases in breast cancer group and 81 cases in benign group. The relationships of clinical characteristics with breast cancer were investigated by multivariate analysis with a logistic regression model.It showed significant differences in levels of nipple discharge CEA (P < 0.001) and CA153 (P = 0.014), but not CA199 (P = 0.856), CA724 (P = 0.171), AFP (P = 0.834) among two groups. Logistic regression analysis demonstrated complaint, age, menopause, abnormal palpable mass, CEA and CA153 were associated with breast cancer. In summary, measurements of CA199, CA724 and AFP in nipple discharge are not of great clinical value. Detecting CEA and CA153 in nipple dischargecould potentially be used for the early detection of breast cancer with in high-risk populations.

  4. Photometric calibrations of the AFP-675 far-ultraviolet cameras experiment

    NASA Astrophysics Data System (ADS)

    Carruthers, George R.; Dohne, Brian C.; Shephard, Kevin K.; Reeb, Susan A. C.; Schmidt, Edward G.

    1994-09-01

    The far ultraviolet cameras experiment (NRL-803), part of the U.S. Air Force Space Test Program's AFP-675 payload, flew aboard the space shuttle Discovery in April - May 1991 (STS-39). While in orbit, the experiment gathered data about sources of far-ultraviolet radiation in near-Earth and distant space. To obtain quantitative information from the data, pre-flight and post-flight calibrations of the flight instruments were required. Calibrations were performed using a vacuum-UV optical collimator and two types of light sources: (a) a vacuum-UV monochromator, whose output wavelength could be varied over the wavelength range 105 - 200 nm; and (b) gas discharge tubes with interference-filter windows, giving monochromatic output at selected wavelengths within this range. Calibrations were of two types (the first performed only before flight): (a) using the far UV cameras as photodiodes; and (b) using the cameras to record images on film, as during flight. In addition, in-flight calibrations are obtained from observations of hot stars or other sources which have been measured by previous space experiments. Results from the calibrations are used to derive absolute far-UV brightnesses of objects from the actual flight data.

  5. Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ -MALDI-MS/MS.

    PubMed

    He, X; Wang, Y; Zhang, W; Li, H; Luo, R; Zhou, Y; Liao, C Li M; Huang, H; Lv, X; Xie, Z; He, M

    2014-01-01

    Hepatocellular carcinoma(HCC) is serious condition associated with a high morbidity and mortality. Therefore is an urgent need to develop novel noninvasive techniques for early diagnosis, particularly for patients with AFP-negative [AFP(-)] HCC. In this study, iTRAQ-MALDI-MS/MS was used to identify differentially expressed proteins in AFP(-) HBV-related HCC compared with non-cancerous hepatitis B virus (HBV) and healthy controls subjects.Serum was obtained from 18 patients with AFP(-) HBV-related HCC, 18 matched patients with HBV without HCC and 18 healthy control subjects. High abundance proteins were removed from serum and the differentially expressed proteins from the three groups were screened out using iTRAQ-MALDI-MS/MS. The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. A total of 24 expressed differential proteins associated with AFP(-) HBV-related HCC were screened out, 15 proteins were up-regulated and 9 down-regulated. The most common molecular function of the 24 differentially expressed proteins was enzyme inhibition. Interaction network of the 24 differentially expressed proteins showed that 14 proteins (C5, KNG1, FN1, LRG1, HRG, SERPINC1, CRP, APOB, SAA1, APCS, C4BPA, CFI, CFB and GSN) were central to the functional network. The expression levels of the GSN protein were down-regulated in AFP(-) HBV-related HCC subjects compared with healthy controls and the HBV group (p<0.01), consistent with the iTRAQ results.The 14 proteins from the serum of AFP(-) HBV-related HCC appeared at the fulcrum of the functional network and were differentially expressed compare to HBV and healthy controls suggesting a possible association with HCC progression.

  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. A Transcriptome Meta-Analysis Proposes Novel Biological Roles for the Antifungal Protein AnAFP in Aspergillus niger

    PubMed Central

    Schäpe, Paul; Müller-Hagen, Dirk; Ouedraogo, Jean-Paul; Heiderich, Caroline; Jedamzick, Johanna; van den Hondel, Cees A.; Ram, Arthur F.; Meyer, Vera

    2016-01-01

    Understanding the genetic, molecular and evolutionary basis of cysteine-stabilized antifungal proteins (AFPs) from fungi is important for understanding whether their function is mainly defensive or associated with fungal growth and development. In the current study, a transcriptome meta-analysis of the Aspergillus niger γ-core protein AnAFP was performed to explore co-expressed genes and pathways, based on independent expression profiling microarrays covering 155 distinct cultivation conditions. This analysis uncovered that anafp displays a highly coordinated temporal and spatial transcriptional profile which is concomitant with key nutritional and developmental processes. Its expression profile coincides with early starvation response and parallels with genes involved in nutrient mobilization and autophagy. Using fluorescence- and luciferase reporter strains we demonstrated that the anafp promoter is active in highly vacuolated compartments and foraging hyphal cells during carbon starvation with CreA and FlbA, but not BrlA, as most likely regulators of anafp. A co-expression network analysis supported by luciferase-based reporter assays uncovered that anafp expression is embedded in several cellular processes including allorecognition, osmotic and oxidative stress survival, development, secondary metabolism and autophagy, and predicted StuA and VelC as additional regulators. The transcriptomic resources available for A. niger provide unparalleled resources to investigate the function of proteins. Our work illustrates how transcriptomic meta-analyses can lead to hypotheses regarding protein function and predict a role for AnAFP during slow growth, allorecognition, asexual development and nutrient recycling of A. niger and propose that it interacts with the autophagic machinery to enable these processes. PMID:27835655

  8. Arginase-1 is a more sensitive marker than HepPar-1 and AFP in differential diagnosis of hepatocellular carcinoma from nonhepatocellular carcinoma.

    PubMed

    Sang, Wei; Zhang, Wei; Cui, Wenli; Li, Xinxia; Abulajiang, Gulinar; Li, Qiaoxin

    2015-05-01

    Distinguishing hepatocellular carcinoma (HCC) from metastatic tumors is a challenging issue, especially in differential diagnosis between poorly differentiated HCC and metastasis tumors. Expression of Arg-1, HepPar-1, and α-fetoprotein (AFP) in 78 cases of HCC, 34 cases of metastatic tumors, and 228 cases of nonhepatocellular tumors of surgical specimens is measured by immunohistochemistry. Arg-1 immunoreactivity was detected in 75 of 78 (96.1 %) cases of HCC, whereas HepPar-1 and AFP immunoreactivity was detected in 63 of 78 (80.7 %) and 40 of 78 (51.3 %) cases of HCC, respectively. HepPar-1 and AFP expression was observed in three of 34 (8.8 %) cases and one of 34 (2.9 %) cases of metastatic tumors, respectively. In contrast, Arg-1 expression was absent in all 34 (0 %) cases of metastatic tumors. The sensitivity, specificity, positive predictive value, and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors and nonhepatocellular tumors are 96.1, 99.6, 98.7, and 98.8 % compared with 80.7, 92.0, 75.0, and 94.1 % for HepPar-1 and 51.3, 97.7, 87.0, and 87.1 % for AFP, respectively. Arg-1 is a more sensitive and better specific marker for HCC compared with HepPar-1 and AFP, indicating that Arg-1 can be easily applied in distinguishing HCC from metastatic tumors.

  9. A Phase II Randomized, Controlled Trial of S-Adenosylmethionine in Reducing Serum α-Fetoprotein in Patients with Hepatitis C Cirrhosis and Elevated AFP.

    PubMed

    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

    2015-09-01

    In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas 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 α-fetoprotein (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 g/d, 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. One hundred ten 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.

  10. Sequential detection of alphafetoprotein-bearing cells in blood stem cell fraction of germ cell tumour patients

    PubMed Central

    Kasahara, T; Hara, N; Bilim, V; Tomita, Y; Saito, K; Obara, K; Takahashi, K

    2001-01-01

    High-dose chemotherapy with peripheral blood stem cell (PBSC) transplantation in advanced germ cell tumour (GCT) patients is widely applied. The aims of this study were: (1) To examine the presence of alphafetoprotein (AFP) bearing tumour cells in PBSC harvests from advanced GCT patients obtained after multiple cycles of induction chemotherapy. (2) To determine whether induction chemotherapy contributed to in vivo purging of the tumour. We evaluated cryopreserved PBSC samples from 5 patients with advanced stage II/III AFP producing GCT. PBSC were separated after the first, second and third cycles of induction chemotherapy. Those samples were analysed using the nested reverse transcription polymerase chain reaction (RT-PCR) method to detect AFP mRNA. Although, in all patients, AFP mRNA was detected in PBSC samples after the first or second cycle of induction chemotherapy, but was not detected in 3 of 4 samples after the third cycle of chemotherapy. Although it is not clear whether tumour cells contaminating PBSC fraction contribute to disease relapse, PBSC harvested after at least 3 cycles of induction chemotherapy might be recommended to avoid such a possibility. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11710823

  11. Mid-trimester maternal serum AFP and hCG as markers of preterm and term adverse pregnancy outcomes.

    PubMed

    Tancrède, Sabrina; Bujold, Emmanuel; Giguère, Yves; Renald, Marie-Hélène; Girouard, Joel; Forest, Jean-Claude

    2015-02-01

    Objectif : Évaluer les coefficients de prévision propres aux taux sériques d’alphafœtoprotéine (AFP) et de gonadotrophine chorionique (hCG) constatés au deuxième trimestre pour ce qui est des issues de grossesse indésirables à médiation placentaire (IGIMP) obtenues avant le terme et à terme. Méthodes : Nous avons tiré, d’une étude de cohorte prospective, des données concernant des femmes nullipares ayant connu une grossesse monofœtale exempte d’aneuploïdie ou d’anomalies fœtales mortelles. Nous avons comparé les taux sériques maternels d’AFP et de hCG (mesurés entre 13 et 17 semaines de gestation et exprimés sous forme de multiples de la médiane [MoM] en fonction de l’âge gestationnel) des femmes ayant connu une IGIMP (prééclampsie, retard de croissance intra-utérin, décès fœtal) avant le terme ou à terme à ceux des femmes qui n’en sont pas venues à connaître de telles complications. Résultats : Au sein d’un groupe de 3 466 femmes nullipares, les taux sériques maternels d’AFP et de hCG étaient connus dans 2 110 cas et 2 125 cas, respectivement. Les femmes qui ont connu une IGIMP avant le terme présentaient des valeurs de MoM pour ce qui est des taux sériques d’AFP (1,4 vs 1,1 MoM; P < 0,01) et de hCG (1,3 vs 1,1 MoM; P < 0,01) plus élevées que celles des femmes du groupe témoin. Bien que la constatation d’un taux sérique de hCG > 2,0 MoM ait été associée à un risque accru d’IGIMP avant le terme (RR, 4,6; IC à 95 %, 2,3 - 9,1), elle n’exerçait aucun effet sur le risque d’IGIMP à terme (RR, 1,1; IC à 95 %, 0,7 - 1,7). La constatation d’un taux sérique maternel d’AFP > 2,0 MoM a également été associée à une hausse considérable du risque d’IGIMP avant le terme (RR, 3,9; IC à 95 %, 1,6 - 9,8); le risque d’IGIMP à terme (RR, 1,2; IC à 95 %, 0,6 - 2,3) n’en était toutefois pas affecté. Conclusion : Au sein de la population à l’étude, les taux s

  12. Types of Stem Cells

    MedlinePlus

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  13. Stem cells.

    PubMed

    Behr, Björn; Ko, Sae Hee; Wong, Victor W; Gurtner, Geoffrey C; Longaker, Michael T

    2010-10-01

    Stem cells are self-renewing cells capable of differentiating into multiple cell lines and are classified according to their origin and their ability to differentiate. Enormous potential exists in use of stem cells for regenerative medicine. To produce effective stem cell-based treatments for a range of diseases, an improved understanding of stem cell biology and better control over stem cell fate are necessary. In addition, the barriers to clinical translation, such as potential oncologic properties of stem cells, need to be addressed. With renewed government support and continued refinement of current stem cell methodologies, the future of stem cell research is exciting and promises to provide novel reconstructive options for patients and surgeons limited by traditional paradigms.

  14. 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…

  15. Alphafetoprotein and atretic follicles in the ovary of the pregnant rat.

    PubMed

    Seralini, G E; Lafaurie, M; Krebs, B; Stora, C

    1986-01-01

    Previous experiments have been conducted concerning the role of alphafetoprotein in genital system blockade in several cases: during adult rat N2-fluorenylacetamide hepatocarcinogenesis, after alphafetoprotein injections into normal adult female rats, during fetal life, and during postnatal and prepuberal development. In these conditions, alphafetoprotein is present at high plasma levels, and the normal cyclic ovarian function is stopped or nonexistent. The degenerating oocytes observed in the ovaries are often AFP-positive by histo-immunolocalization. Pregnancy corresponds to a physiological state in which alphafetoprotein levels are high while the gonadal activity is not characterized by ovulatory cycles. In order to assess our hypothesis, alpha-fetoprotein was studied in the ovary of pregnant rats from day 18 to 21 of gestation by an immunofluorescent technique, and alpha-fetoprotein was assayed in plasma samples. The results of this work show that, during pregnancy, follicular maturation is blocked at the antral stage, and the follicles contain degenerating oocytes that are AFP-positive in immunofluorescence. In conclusion, we suggest that the alpha-fetoprotein produced by the fetal liver and the yolk sac is disseminated in the amniotic fluid and passes through the placenta, and then reaches the ovarian follicles and the oocytes. The possible role of alphafetoprotein in follicular atresia is discussed.

  16. Autoradiography of "oval cells" appearing rapidly in the livers of rats fed N-2-fluorenylacetamide in a choline devoid diet.

    PubMed

    Sell, S; Osborn, K; Leffert, H L

    1981-01-01

    Autoradiographic analysis of liver sections from rats fed the hepatocarcinogen N-2-fluorenylacetamide (FAA) in a choline devoid (CD) diet suggests that proliferating small "oval" cells arise from a few small portally-situated cells, and spread rapidly across the entire liver lobule. Small cells with detectable grains are first located where liver plates meet the portal areas. This cell type gradually increases in number over a 10-12 day period, then proliferates rapidly. After 28 days, microscopic nodules consisting of heavily labeled large eosinophilic cells appear, whereas residual hepatocytes are not labeled. Combined immunofluorescent and autoradiographic labeling studies reveal that many of the small cells contain AFP; approximately half of the alpha-fetoprotein-containing cells are labeled with [3H]thymidine (dT). Feeding CD-FAA diets to rats with hepatocytes prelabeled with [3H]dT after 70% hepatectomy 7 weeks earlier provides data which suggest that small "oval" cells do not arise from prelabeled hepatocytes but, instead, infiltrate the prelabeled hepatocytes during the diet induced proliferative phase. We conclude that "oval" cells arise from a small number of portal cells, not from hepatocytes. Exact identification of the oval cell precursor is not possible, but it could be a "stem" cell. Although hepatocyte-like properties are found in small cells (e.g., albumin staining), there is no evidence that they differentiate into normally functioning hepatocytes.

  17. 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.

  18. Superfund Record of Decision (EPA Region 9): Tucson International Airport Area, Operable Unit 3 (AFP 44), Tucson, AZ, September 28, 1998

    SciTech Connect

    Not Available

    1999-05-01

    Air Force Plant 44 (AFP 44) is located within the Tucson International Airport Area Superfund Site, Tucson, Arizona, and is identified as such on the National Priorities List. The Air Force has decided that excavation and offsite disposal in a Resource Conservation and Recovery Act (RCRA) Class I landfill with solidification/stabilization (S/S) is the preferred remedy for excavated metals-contaminated materials under CERCLA for these three specific sites and sources.

  19. The sandwich-type electrochemiluminescence immunosensor for α-fetoprotein based on enrichment by Fe3O4-Au magnetic nano probes and signal amplification by CdS-Au composite nanoparticles labeled anti-AFP.

    PubMed

    Zhou, Hankun; Gan, Ning; Li, Tianhua; Cao, Yuting; Zeng, Saolin; Zheng, Lei; Guo, Zhiyong

    2012-10-09

    A novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was fabricated on a glassy carbon electrode (GCE) for ultra trace levels of α-fetoprotein (AFP) based on sandwich immunoreaction strategy by enrichment using magnetic capture probes and quantum dots coated with Au shell (CdS-Au) as the signal tag. The capture probe was prepared by immobilizing the primary antibody of AFP (Ab1) on the core/shell Fe(3)O(4)-Au nanoparticles, which was first employed to capture AFP antigens to form Fe(3)O(4)-Au/Ab1/AFP complex from the serum after incubation. The product can be separated from the background solution through the magnetic separation. Then the CdS-Au labeled secondary antibody (Ab2) as signal tag (CdS-Au/Ab2) was conjugated successfully with Fe(3)O(4)-Au/Ab1/AFP complex to form a sandwich-type immunocomplex (Fe(3)O(4)-Au/Ab1/AFP/Ab2/CdS-Au), which can be further separated by an external magnetic field and produce ECL signals at a fixed voltage. The signal was proportional to a certain concentration range of AFP for quantification. Thus, an easy-to-use immunosensor with magnetic probes and a quantum dots signal tag was obtained. The immunosensor performed at a level of high sensitivity and a broad concentration range for AFP between 0.0005 and 5.0 ng mL(-1) with a detection limit of 0.2 pg mL(-1). The use of magnetic probes was combined with pre-concentration and separation for trace levels of tumor markers in the serum. Due to the amplification of the signal tag, the immunosensor is highly sensitive, which can offer great promise for rapid, simple, selective and cost-effective detection of effective biomonitoring for clinical application.

  20. Combined Evaluation of AFP, CA15-3, CA125, CA19-9, and CEA Tumor Markers in Patients with Hepatitis B and C

    PubMed Central

    ASSMAR, Mehdi; YEGANEH, Sara; MANSOURGHANAEI, Fariborz; AMIRMOZAFARI, Nour

    2016-01-01

    Background: This study aimed to determine the role of tumor markers AFP, CA15-3, CA125, CA19-9 and CEA in patients with hepatitis B and C. Methods: This descriptive cross-sectional study was performed from Oct 2012 to Oct 2014. Serum samples of 129 patients with hepatitis B and C referred to Guilan Liver and Digestive Disease Research Center in Rasht, Iran were collected and checked for the existence of the listed tumor markers by ELISA. Results: No increase in serum levels of tumor marker CA19-9, CEA and CA15-3 were seen in patients with hepatitis (P>0.05). In patients with hepatitis B, increase in CA125 were observed (P=0.03). In hepatitis C patients, there was an increase in AFP levels (P=0.03). Conclusion: The levels of AFP and CA125 markers were high in hepatitis C and hepatitis B, respectively. However, the increased levels were not seen is malignancy. Due to the small sample size, further study is necessary to find the reasons of the increase. PMID:28053931

  1. Molecular Epidemiology and Recombination of Human Enteroviruses from AFP surveillance in Yunnan, China from 2006 to 2010

    PubMed Central

    Tang, Jingjing; Yoshida, Hiromu; Ding, Zhengrong; Tao, Zexin; Zhang, Jie; Tian, Bingjun; Zhao, Zhixian; Zhang, Lifen

    2014-01-01

    The study represents the genetic overview of non-polio enteroviruses (NPEV) isolated from acute flaccid paralysis (AFP) cases in Yunnan Province from 2006 to 2010. Molecular typing based on VP1 nucleotide sequence was carried out on 98 NPEV isolates, and 33 serotypes were identified. EV-B was detected most frequently with an overall prevalence of 71.4%, followed by EV-A (18.4%) and EV-C (10.2%). No EV-D was identified. NPEV positive rate was higher in children <3 years of age and in summer and autumn months. Clinically, 68.4% patients presented with fever, and 16 cases (16.3%) were classified as Guillain-Barré syndrome, followed by myositis (13.3%). The phylogenetic analysis on the VP1 and 3D regions of prevalent serotypes provided evidence for recombination events among them. EV-A71, an important pathogen previously demonstrated to be associated with paralysis, had also been detected (n = 8) in this study and they all belonged to genotype C4. Great genetic divergence between Yunnan isolates and strains from other regions of the world was revealed. The findings of the study are of great importance for further research on molecular evolution of EV under the circumstance of no specialized EV surveillance system in China. PMID:25317568

  2. Construction of the optical part of a time-of-flight detector prototype for the AFP detector.

    PubMed

    Nozka, L; Adamczyk, L; Avoni, G; Brandt, A; Buglewicz, P; Cavallaro, E; Chiodini, G; Chytka, L; Ciesla, K; Davis, P M; Dyndal, M; Grinstein, S; Hamal, P; Hrabovsky, M; Janas, K; Jirakova, K; Kocian, M; Komarek, T; Korcyl, K; Lange, J; Mandat, D; Michalek, V; Paz, I Lopez; Northacker, D; Rijssenbeek, M; Seabra, L; Schovanek, P; Staszewski, R; Swierska, P; Sykora, T

    2016-11-28

    We present the construction of the optical part of the ToF (time-of-flight) subdetector prototype for the AFP (ATLAS Forward Proton) detector. The ToF detector in conjunction with a 3D silicon pixel tracker will tag and measure protons originating in central exclusive interactions p + p → p + X + p, where the two outgoing protons are scattered in the very forward directions. The ToF is required to reduce so-called pileup backgrounds that arise from multiple proton interactions in the same bunch crossing at high luminosity. The background can fake the signal of interest, and the extra rejection from the ToF allows the proton tagger to operate at the high luminosity required for measurement of the processes. The prototype detector uses fused silica bars emitting Cherenkov radiation as a relativistic particle passes through it. The emitted Cherenkov photons are detected by a micro-channel plate multi-anode Photomultiplier Tube (MCP-PMT) and processed by fast electronics.

  3. 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

  4. STEM Education.

    PubMed

    Xie, Yu; Fang, Michael; Shauman, Kimberlee

    2015-08-01

    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.

  5. Sustained release of the candidate antiretroviral peptides T-1249 and JNJ54310516-AFP from a rod insert vaginal ring.

    PubMed

    Murphy, Diarmaid J; Amssoms, Katie; Pille, Geert; Clarke, Aileen; O'Hara, Marc; van Roey, Jens; Malcolm, R Karl

    2016-06-01

    Administration of biomacromolecular drugs in effective quantities from conventional vaginal rings is hampered by poor drug permeability in the polymers from which rings are commonly constructed. Here, we report the formulation development and testing of rod insert rings for sustained release of the candidate antiretroviral peptides T-1249 and JNJ54310516-AFP (JNJ peptide), both of which have potential as HIV microbicides. Rod inserts were prepared comprising antiviral peptides T-1249 or JNJ peptide in combination with a hydrophilic excipient (sodium chloride, sodium glutamate, lactose or zinc acetate) dispersed at different loadings within a medical grade silicone elastomer. The inserts were tested for weight change and swelling when immersed in simulated vaginal fluid (SVF). Dye migration into the inserts was also assessed visually over 28 days. In vitro release of T-1249 and JNJ peptide from rings containing various insert types was tested. Weight change and degree of swelling of rods immersed in SVF was dependent on the type and concentration of excipient present. The rods displayed the following rank order in terms of weight change: sodium glutamate > zinc acetate ≈ sodium chloride > lactose. The weight change and degree of swelling of the inserts did not correlate with the level of dye uptake observed. In vitro release of T-1249 was improved through addition of lactose, sodium chloride and sodium glutamate, while release of JNJ peptide was improved through addition of sodium chloride or sodium glutamate. Sustained release of hydrophobic peptides can be achieved using a rod insert ring design formulated to include a hydrophilic excipient. Release rates were dependent upon the type of excipient used. The degree of release improvement with different inserts partially reflects their ability to imbibe surrounding fluid and swell in aqueous environments.

  6. Improved Survival and Initiation of Differentiation of Human Induced Pluripotent Stem Cells to Hepatocyte-Like Cells upon Culture in William’s E Medium followed by Hepatocyte Differentiation Inducer Treatment

    PubMed Central

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-01-01

    Background Hepatocyte differentiation inducer (HDI) lacks both glucose and arginine, but is supplemented with galactose and ornithine, and is added together with other reagents such as apoptosis inhibitor and oncostatin M. Although human induced pluripotent stem (iPS) cells initiate hepatocyte differentiation, most die within 7 days. In this study, we investigated both HDI and conventional media for their potential to improve cell survival. Materials and Methods 201B7 iPS cells were cultured in conventional media. This consisted of three cycles of 5-day culture in William’s E (WE) medium, followed by a 2-day culture in HDI. Results Expression levels of α-feto protein (AFP) were higher in cells cultured in WE and in Dulbecco’s Modified Eagle’s Medium/Nutrient F-12 Ham (DF12). 201B7 cells expressed the highest AFP and albumin (ALB) when cultured in HDI for 2 days following 7-day culture in WE. After three cycles of 5-day culture in WE followed by 2 days in HDI, 201B7 cells expressed AFP and ALB 54 ± 2.3 (average ± standard deviation) and 73 ± 15.1 times higher, respectively, than those cultured in ReproFF (feeder-free condition). Conclusion 201B7 cells survived culture in WE for 7 days followed HDI for 2 days. After three cycles of culture under these conditions, hepatocyte differentiation was enhanced, as evidenced by increased AFP and ALB expression. PMID:27073925

  7. 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

  8. Stem Cell Basics

    MedlinePlus

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  9. 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

    2003-01-03

    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.

  10. 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…

  11. 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…

  12. 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

  13. Preoperative prognostic values of α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients with hepatocellular carcinoma for living donor liver transplantation

    PubMed Central

    Kim, Seok-Hwan; Kim, Wan-Joon; Kang, Woo-Hyoung; Kwon, Jae Hyun; Jwa, Eun Kyung; Cho, Hwui-Dong; Ha, Su-Min; Chung, Yong-Kyu; Lee, Sung-Gyu

    2016-01-01

    Background Adult living donor liver transplantation (LDLT) is one of the best treatments for hepatocellular carcinoma (HCC). However, when recurrence of HCC after LDLT occurs, the prognosis is poor because of rapid progression. Preoperative level of α-fetoprotein (AFP) and protein induced by vitamin K antagonist-II (PIVKA-II) reportedly correlate with recurrence of HCC after LDLT. Methods We examined AFP and PIVKA-II preoperatively as predictors of HCC recurrence in 461 patients who underwent LDLT using right liver graft for HCC from May 2007 to December 2013. Results Among these, 77 patients (16.7%) who experienced recurrence were retrospectively reviewed. Multivariate analysis revealed tumor size >5 cm, AFP >150 nag/mol and PIVKA-II >100 maul/mol as significant independent risk factors for recurrence. The median time to recurrence was 10 months. The median survival time after recurrence was 26 months, and the 1-, 3- and 5-year survival rates after recurrence were 80.5%, 58%, and 28.3% respectively. Conclusions Preoperatively, not only morphology of the tumor but also AFP and PIVKA-II levels can offers important information for the recurrence after LDLT for HCC. Thus, combination of tumor markers might be used for expansion of pre-existing strict selection criteria of liver transplantation for HCC. PMID:28124000

  14. 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.

  15. The role of radioimmunodetection in the management of testicular cancer

    SciTech Connect

    Javadpour, N.; Kim, E.E.; DeLand, F.H.; Salyer, J.R.; Shah, U.; Goldenberg, D.M.

    1981-07-03

    Five patients with testicular cancer received an intravenous injection of between 1 and 2.5 mCi of iodine 131-labeled antibody to human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP), followed by total-body photoscanning to visualize areas of abnormal radioactivity. Blood-pool and nontarget sites of radioactivity were reduced by subtracting the images derived by injection of technetium Tc 99m-labeled components from the iodine 131 scans. The HCG-immune scintiscans proved helpful in tumor localization and in the selection of appropriate therapy, while the AFP scan presented corroborative evidence of widespread tumor. Elevated serum levels of these two markers did not hinder successful tumor detection and localization by this method of radioimmunodetection. Cancer radioimmunodetection with antibodies to HCG and to AFP appears to be a useful procedure for the pretreatment and posttreatment evaluation of patients with testicular cancer and can reveal sites of tumor not detected by other methods.

  16. 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.

  17. 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.

  18. Stem Cell Information: Glossary

    MedlinePlus

    ... cells (skeletal stem cells) Cell-based therapies Cell culture Cell division Chromosome Clone Cloning Cord blood stem cells Culture medium Differentiation Directed differentiation DNA Ectoderm Embryo Embryoid ...

  19. 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.

  20. 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.

  1. Platinum-based Chemotherapy in Primary Advanced Seminoma—a Retrospective Analysis: Treatment Results at the Northern Israel Oncology Center (1989–2010)

    PubMed Central

    Stein, Moshe E.; Drumea, Karen; Charas, Tomer; Gershuny, Anthony; Ben-Yosef, Rahamim

    2014-01-01

    Objective: Over the past 30 years, great strides have been made in the treatment of disseminated testicular tumors. Despite the low number of patients and the rarity of studies concerning primary advanced seminoma, the efficacy of chemotherapy is clear, mainly 3–4-cisplatin-based chemotherapy. Aiming to contribute to the understanding and implementation of proper chemotherapeutic management in advanced seminoma patients, we retrospectively summarized our experience with 26 patients who were referred for platinum-based chemotherapy, post-orchiectomy to the Northern Israel Oncology Center between 1989 and 2010. Response rate, side effects, and long-term outcome were investigated. Methods: Before chemotherapy, meticulous staging was done, including tumor markers (B-human chorionic gonadotropin (B-HCG), alpha-fetoprotein (AFP), and lactic dehydrogenase (LDH)), and abdominal and pelvic computerized tomography (CT) scans were carried out. Results: All 26 treated patients achieved complete remission, clinically and symptomatically, with normalization of their CT scans. At a median follow-up of 120 months (range, 24–268 months) all patients are alive, without evidence of recurrent disease. One patient whose disease recurred twice achieved a third complete remission following salvage treatment with high-dose chemotherapy and autologous peripheral stem cell transplantation. Another patient, who preferred surveillance, relapsed abdominally after 9 months but achieved long-standing complete remission with cisplatin-based chemotherapy. Both these patients are alive with no evidence of disease. Three patients recovered uneventfully from bleomycin-induced pneumonitis. Conclusions: Advanced seminoma is a highly curable disease using platinum-based chemotherapy. Our study confirms the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma. PMID:24498512

  2. Dyslipidemia in pregnancy may contribute to increased risk of neural tube defects -a pilot study in north Indian population.

    PubMed

    Gupta, Supriya; Arora, Sarika; Trivedi, S S; Singh, Ritu

    2009-04-01

    Neural tube defects are congenital structural abnormalities of the brain and vertebral column resulting from improper or non-timely closure of the neural tube. Prevalence of neural tube defects is reported to be higher among women with diabetes mellitus and obesity. This study was designed to investigate the relation between the presence of dyslipidemia in antenatal patients and the risk of fetal neural tube defects. The present study was an observational, cross-sectional study involving 129 pregnant women in 16 to 18 weeks gestation period. Of these, 80 women had normal pregnancies and 49 were clinically high-risk cases for neural tube defects. Fasting blood samples were analyzed for blood sugar and lipid profile by enzymatic assay and alpha-fetoprotein levels using Enzyme Immunoassay. Alpha-fetoprotein (AFP) values were converted to Multiples of Median (MoM) appropriate for the gestational age. Based on AFP values, women were labeled as screen negative (AFP <2 MoM, n= 102) and screen positive (AFP > 2 MoM, n =27). Screen positive women were further evaluated by ultrasound and 21 women were found to carry a neural tube defects positive pregnancy. Statistical analysis was done on SPSS software. Body weight of the women showed a significant positive correlation with serum triglycerides, plasma sugar and AFP MoM values. A significant difference was observed in serum cholesterol levels (p= 0.038), triglycerides (p=0.001) and plasma sugar levels (p=0.002) between normal women and those with neural tube defects positive pregnancy. The Odds ratio for neural tube defects risk in dyslipidemic cases was 24.23 (CI 4.73 - 148.60) with a relative risk of 12.12. Dyslipidemia especially hypertriglyceridemia was found to be significantly associated with fetal neural tube defects.

  3. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  4. 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.

  5. 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

  6. Stem Cell Transplant

    MedlinePlus

    ... transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or ... A bone marrow transplant is also called a stem cell transplant. A bone marrow transplant may be necessary ...

  7. 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.

  8. 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…

  9. 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…

  10. Nail stem cells.

    PubMed

    Sellheyer, Klaus

    2013-03-01

    Our knowledge on stem cells of the hair follicle has increased exponentially after the bulge was characterized as the stem cell niche two decades ago. In contrast, little is known about stem cells in the nail unit. Whereas hair follicles are plentiful and easy to access, the human body has only twenty nails and they are rarely biopsied. Therefore, examining fetal material offers unique advantages. In the following mini-review, our current knowledge on nail stem cells is summarized and analogies to the hair follicle stem cells are drawn.

  11. Ferrocenemonocarboxylic-HRP@Pt nanoparticles labeled RCA for multiple amplification of electro-immunosensing.

    PubMed

    Su, Huilan; Yuan, Ruo; Chai, Yaqin; Mao, Li; Zhuo, Ying

    2011-07-15

    A multiple amplification immunoassay was proposed to detect alpha-fetoprotein (AFP), which was based on ferrocenemonocarboxylic-HRP conjugated on Pt nanoparticles as labels for rolling circle amplification (RCA). Firstly, the capture antibody (anti-AFP) was immobilized on glass carbon electrode (GCE) deposited nano-sized gold particles. After a typical immuno-sandwich protocol, primary DNA was immobilized by labeling secondary antibody, which acted as a precursor to initiate RCA. The products of RCA provide large amount of sites to link detection DNAs, which were labeled by signal probes (ferrocenemonocarboxylic) and horseradish peroxidase (HRP). Moreover, the enzymatic amplification signals could be produced by the catalysis of HRP and Pt nanoparticles with the addition of H₂O₂. These lead to multiple amplification signals monitoring by electrochemical instrument and further resulted in high sensitivity of the immunoassay with the detection limit of 1.7 pg/mL.

  12. [Diagnostic value of tumor markers in pleural effusions].

    PubMed

    Botte, G; Laferrere, L; Etchepare, S; Dalurzo, D; Duhart, J E; Adaro, F V

    1990-01-01

    In order to discriminate between benign and malignant effusions, the value of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and beta subunit of human chorionic gonadotropin (GNCH Sub-beta) has been estimated in pleural exudates. A sample of 65 patients, 33 with a malignant (histologically and/or cytologically established) and 32 with a benign effusion was analysed. Only mean CEA in malignant effusions was significantly higher than in benign effusions (p less than 0.01). In the detection of malignant effusion CEA showed a sensitivity of 57% and a specificity of 97%; AFP a sensitivity of 9% and a specificity of 97% and GNCH Sub beta a sensitivity of 9% and a specificity of 90%.

  13. External quality control results for hormones, tumor markers and CRP testing.

    PubMed

    Tatsumi, N; Kawano, K; Takubo, T; Nakamura, H; Tsuda, I

    1999-01-01

    Most hormones, tumor markers, C-reactive protein, and rheumatoid factor (RF) are measured immunologically. Immunological methods based on the antigen-antibody reaction have certain specific problems, including their principle of determination, character of antibodies used, reaction conditions, and others. Free thyroxine (FT4) and thyroid stimulating hormone (TSH), as well as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate antigen, carcinoantigen 19-9 (CA 19-9), and CA 125 are very commonly measured in the routine medical laboratory. Authentic materials can be obtained for hormones and CRP, and efforts to improve quality control and standardization have been made for years. Results of surveillance for FT4, TSH, and AFP were not poor, but inter-laboratory differences for CEA, CA 19-9, and RF were not insignificant.

  14. 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.

  15. Liver cancer stem cells.

    PubMed

    Sell, Stewart; Leffert, Hyam L

    2008-06-10

    In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.

  16. 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.

  17. 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.

  18. Role of superoxide dismutase in hepatitis B virus-related hepatocellular carcinoma

    PubMed Central

    Zhang, Xiaolian; Lu, Yu; Rong, Chengzhi; Yang, Dongmei; Li, Shan; Qin, Xue

    2016-01-01

    Background: Reactive oxygen species (ROS) play important roles in hepatocarcinogenesis. Superoxide dismutase (SOD) is involved in the repair of ROS. Serum alpha-fetoprotein (AFP) is the “golden marker” for diagnosing hepatocellular carcinoma (HCC), and one major shortcoming of its use is that it is insensitive for the early detection of HCC. Therefore, we evaluated serum SOD levels and their association with AFP in hepatitis B virus (HBV)-related HCC. Materials and Methods: A total of 279 subjects were divided into three groups: 99 HBV patients with HCC, 73 HBV patients without HCC, and 107 sex- and age-matched healthy controls. Serum levels of SOD were assayed using colorimetry, while AFP levels were measured by electrochemiluminescence immunoassay. Results: A highly significant elevation was found in AFP in HBV-with HCC patients compared to HBV-without HCC patients and control subjects (P < 0.001). Alternatively, serum SOD levels were significantly decreased in patients with HCC compared to HBV patients without HCC and healthy controls (P < 0.001). Furthermore, serum SOD was negatively correlated with AFP (r = −0.505, P < 0.001) in HBV-with HCC patients. Conclusion: SOD and AFP might be simultaneously evaluated to improve the HCC detection rate. PMID:28163740

  19. 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…

  20. 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.

  1. Stress and stem cells.

    PubMed

    Tower, John

    2012-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress.

  2. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness 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 ...

  3. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants A ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  4. 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.

  5. Myeloproliferative neoplasm stem cells.

    PubMed

    Mead, Adam J; Mullally, Ann

    2017-03-23

    Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2, CALR, or MPL The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC.

  6. Learn About Stem Cells

    MedlinePlus

    ... develops and ages, the number and type of stem cells changes. Totipotent cells are no longer present after dividing into the cells that generate the placenta and umbilical cord. Pluripotent cells ... organs and tissues. The stem cells that stay in your body throughout your ...

  7. 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…

  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. 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…

  10. 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…

  11. Colorectal cancer stem cells.

    PubMed

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  12. 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…

  13. 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…

  14. 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.

  15. The maintaining of the active laboratory-based surveillance of the acute flaccid paralysis (AFP) cases in Romania in the framework of the strategic plan of the global polio eradication initiative.

    PubMed

    Băicuş, Anda; Persu, Ana; Combiescu, Mariana; Aubert-Combiescu, A

    2007-01-01

    Until 2008 poliomyelitis was controlled in Romania by predominantly using Oral Poliovirus Vaccine Sabin (OPV); the alternative vaccination schedule (IPV formalin Inactivated Poliovirus Vaccine/OPV) will be implemented starting September 2008. The vaccination coverage with 4 doses of TOPV (trivalent oral polio vaccine) in the first 14 months of life has been > 90% since 1980. In Romania, the risk of the Vaccine-Associated Paralytic Poliomyelitis cases (VAPP) decreased from less than 2 VAPP cases/year in the 1995-2006 interval to 0 VAPP cases in 2007. The serological study was performed in 2006-2007 only in cases with pair serum samples from 28 acute flaccid paralysis (AFP) cases (age = 3 months - 14 years) and from 45 facial paralysis (FP) cases (age -6 months - 4 years 9 months). A high level of vaccinal coverage was shown for all poliovirus serotypes: >95% in AFP serum samples investigated; and for FP serum samples investigated the levels of antibodies against poliovirus (PV) serotypes were 98% for PV type 1; 87% for PV type 2: and 89% for PV type 3. If the European region is polio free since 2002, the risk of wild PV importation from endemic region remains present. The laboratory capacity for the fast detection and molecular investigations of the emergence of the new epidemic strains and a high level of population immunity must be maintained. A national seroprevalence study concerning all three PV serotypes must be performed.

  16. A proposed unified mechanism for the reduction of human breast cancer risk by the hormones of pregnancy.

    PubMed

    Jacobson, Herbert I; Lemanski, Nicole; Agarwal, Anu; Narendran, Amithi; Turner, Kelvin E; Bennett, James A; Andersen, Thomas T

    2010-02-01

    Parity in women is associated with reduced lifetime risk of breast cancer, and hormones of pregnancy [estrogen (E), progesterone (P), human chorionic gonadotropin (hCG)] are implicated. Parity also reduces mammary cancer risk in carcinogen-exposed rats, and administering pregnancy hormones to these animals is similarly effective. Because pregnancy hormones are also able to stimulate cancer growth, we proposed to resolve this dichotomy by determining whether administered pregnancy hormones elicit the cancer-inhibiting agent alpha-fetoprotein (AFP) from the liver, which would implicate AFP as a proximal effector of hormonal anticancer activity. Accordingly, we treated groups of nitrosomethylurea-exposed rats with saline, E(3), E(2) + P, E(3) + P, hCG, or allowed them to experience pregnancy, and then monitored mammary cancer incidence and serum levels of AFP over time. Each hormone treatment reduced mammary cancer incidence and elevated serum AFP levels. To challenge human tissues, human HepG2 liver cells in culture were treated with the same hormonal agents. Each hormone regimen increased the levels of AFP in the culture medium. Medium containing AFP elicited by hCG inhibited the E(2)-stimulated proliferation of cultured human MCF7 breast cancer cells, whereas hCG alone did not inhibit their growth. Furthermore, antibodies to AFP neutralized the growth-inhibiting effect of AFP-containing HepG2 medium. We conclude that in the treatment of carcinogen-exposed rats with the hormones of pregnancy, and by inference in women who have experienced pregnancy, that AFP is a proximal agent that inhibits mammary gland cancer.

  17. 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.

  18. 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...

  19. 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

  20. Glypican 3 as a Serum Marker for Hepatoblastoma

    PubMed Central

    Zhou, Shengmei; O’Gorman, Maurice R. G.; Yang, Fusheng; Andresen, Kevin; Wang, Larry

    2017-01-01

    Hepatoblastoma (HB) is the most common primary liver cancer in children. The conventional serum marker for HB, alpha-fetoprotein (AFP), has its limitations. Novel serum markers need to be explored. Glypican 3 (GPC3) has been reported to be an excellent histological immunomarker for HB. However, the clinical value of serum GPC3 in patients with HB is unknown. A total of 184 serum samples were tested for both GPC3 by ELISA, and AFP by immunometric assay. Of these, 134 were from 32 patients with HB at three treatment stages, 30 from age-matched patients with benign hepatobiliary disorders (BHD) and 20 from age-matched “normal controls”(NC). We found that the GPC3 levels in HB pretreatment group were significantly higher than those in NC group and HB remission group but not statistically different from those in BHD group and HB during treatment group. In contrast, AFP showed significant differences among different groups. The areas under the receiver operating curve (AUROC) value, sensitivity and specificity of GPC3 for HB pretreatment group versus all controls were all significantly lower than those of AFP. Serum GPC3 levels were not associated with prognostic parameters. We concluded that GPC3 is inferior to AFP as a serum marker for HB. PMID:28378832

  1. Simultaneous electrochemical immunoassay using graphene-Au grafted recombinant apoferritin-encoded metallic labels as signal tags and dual-template magnetic molecular imprinted polymer as capture probes.

    PubMed

    Wang, De; Gan, Ning; Zhang, Huairong; Li, Tianhua; Qiao, Li; Cao, Yuting; Su, Xiurong; Jiang, Shan

    2015-03-15

    A novel electrochemical multiplexed immunoassay was designed for simultaneous determination of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) using recombinant apoferritin-encoded metallic nanoparticles (rApo-M) as labels and dual-template magnetic molecularly imprinted polymers (MMIPs) as capture probes. The labels were prepared by loading recombinant apoferritin (r-Apo) and separately immobilize primary antibodies (anti-AFP and anti-CEA) via Au nanoparticles of in site growth on graphene (G). The capture probes were synthesized by self-polymerization of dopamine (DA) on the Fe3O4 nanoparticles (Fe3O4 NPs) and using AFP and CEA as the template proteins, which were used to enrich the targets simultaneously. After a sandwich-type immunoreaction, the labels were captured to the surface of MMIPs. The subsequent electrochemical stripping analysis of the metal components from the immunocomplex provide a means for quantification of targets based on the peak currents of Cd and Pb. Experimental results showed the immunoassay enabled the simultaneous determination of AFP and CEA in a single run with wide dynamic ranges of 0.001-5ngmL(-1). And the detection limits of AFP and CEA were 0.3 and 0.35pgmL(-1) (S/N=3), respectively. These results suggested that the proposed multiplexed immunoassay would be applied for clinical screening of other biomarkers.

  2. [On plant stem cells and animal stem cells].

    PubMed

    You, Yun; Jiang, Chao; Huang, Lu-Qi

    2014-01-01

    A comparison of plant and animal stem cells can highlight core aspects of stem-cell biology. In both kingdoms, stem cells are defined by their clonogenic properties and are maintained by intercellular signals. The signaling molecules are different in plants and animals stem cell niches, but the roles of argonaute and polycomb group proteins suggest that there are some molecular similarities.

  3. Nuclear receptor regulation of stemness and stem cell differentiation

    PubMed Central

    Jeong, Yangsik

    2009-01-01

    Stem cells include a diverse number of toti-, pluri-, and multi-potent cells that play important roles in cellular genesis and differentiation, tissue development, and organogenesis. Genetic regulation involving various transcription factors results in the self-renewal and differentiation properties of stem cells. The nuclear receptor (NR) superfamily is composed of 48 ligand-activated transcription factors involved in diverse physiological functions such as metabolism, development, and reproduction. Increasing evidence shows that certain NRs function in regulating stemness or differentiation of embryonic stem (ES) cells and tissue-specific adult stem cells. Here, we review the role of the NR superfamily in various aspects of stem cell biology, including their regulation of stemness, forward- and trans-differentiation events; reprogramming of terminally differentiated cells; and interspecies differences. These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell). PMID:19696553

  4. 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.

  5. Hematopoietic Stem Cells Therapies.

    PubMed

    Chivu-Economescu, Mihaela; Rubach, Martin

    2017-01-01

    Stem cell-based therapies are recognized as a new way to treat various diseases and injuries, with a wide range of health benefits. The goal is to heal or replace diseased or destroyed organs or body parts with healthy new cells provided by stem cell transplantation. The current practical form of stem cell therapy is the hematopoietic stem cells transplant applied for the treatment of hematological disorders. There are over 2100 clinical studies in progress concerning hematopoietic stem cell therapies. All of them are using hematopoietic stem cells to treat various diseases like: cancers, leukemia, lymphoma, cardiac failure, neural disorders, auto-immune diseases, immunodeficiency, metabolic or genetic disorders. Several challenges are to be addressed prior to developing and applying large scale cell therapies: 1) to explain and control the mechanisms of differentiation and development toward a specific cell type needed to treat the disease, 2) to obtain a sufficient number of desired cell type for transplantation, 3) to overcome the immune rejection and 4) to show that transplanted cells fulfill their normal functions in vivo after transplants.

  6. Successful treatment of a case with pancreatic neuroendocrine carcinoma with focal hepatoid differentiation: a case report and literature review

    PubMed Central

    Xin, Bao-Bao; Li, Jian-Ang; Han, Xu; Zhao, Jing; Ji, Yuan; Lou, Wen-Hui; Xu, Xue-Feng

    2014-01-01

    A 33-year-old Chinese woman was admitted to our hospital because of an elevated serum alpha-fetoprotein (AFP) level (300 ng/mL) found in a regular medical checkup. Computed tomography imaging of the abdomen revealed a 1.6 × 2.2 cm low-attenuation mass in the head of the pancreas, with no enlarged lymph nodes and no metastatic liver nodules, and a pancreaticoduodenectomy was performed and the tumor was completely removed. The tumor was solid, unencapsulated and poorly demarcated, measuring 2 × 1.4 × 1.8 cm, and the cut surface was grey-yellowish. Histologically, most of the areas of the tumor were composed of small monotonous and round shaped neuroendocrine cells, and approximately 20% of the areas were cells with indistinct cytoplasmic borders, large oval nuclei, prominent nucleoli and abundant eosinophilic cytoplasm, resembling the appearance of HCC. Immunohistochemical stains revealed that the neuroendocrine areas were diffusely positive for chromogranin, and the hepatoid areas showed diffuse and strong positive reaction to AFP. After surgery the AFP level reduced to normal. She received six cycles of postoperative chemotherapy and three years after the surgery was found to have an elevated serum AFP level again which gave rise to the suspicion of tumor recurrence, and a positron emission tomography-computed tomography confirmed the speculation by showing a hypermetabolic lymph node behind the body of the pancreas. She then underwent radiotherapy and the AFP level reduced to normal. Up till now she has survived 46 months since the initial diagnosis. This case and previous cases suggest that the serum AFP could be a useful marker for early detection of the disease, but careful differential diagnosis should be performed, and AFP could also be a marker for evaluation of therapeutic response and recurrence of the AFP-producing hepatoid carcinomas of pancreas. PMID:25419403

  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. Fifth Annual Stem Cell Summit.

    PubMed

    Knowlton, Daniel

    2010-04-01

    The Fifth Annual Stem Cell Summit, held in New York, included topics covering new commercial developments in the research field of stem cell-based therapies. This conference report highlights selected presentations on embryonic and adult stem cells, stem cell-based therapies for the treatment of orthopedic and cardiovascular indications and inflammatory diseases, as well as technologies for processing and storing stem cells. Investigational therapies discussed include placental expanded (PLX) cells (Pluristem Therapeutics Inc), StemEx (Gamida-Teva Joint Venture/Teva Pharmaceutical Industries Ltd) and remestemcel-L (Osiris Therapeutics Inc/Genzyme Corp/JCR Pharmaceuticals Co Ltd/ Mochida Pharmaceutical Co Ltd).

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  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. 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

  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. 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

  1. Reversing breast cancer stem cell into breast somatic stem cell.

    PubMed

    Wijaya, L; Agustina, D; Lizandi, A O; Kartawinata, M M; Sandra, F

    2011-02-01

    Stem cells have an important role in cell biology, allowing tissues to be renewed by freshly created cells throughout their lifetime. The specific micro-environment of stem cells is called stem cell niche; this environment influences the development of stem cells from quiescence through stages of differentiation. Recent advance researches have improved the understanding of the cellular and molecular components of the micro-environment--or niche--that regulates stem cells. We point out an important trend to the study of niche activity in breast cancers. Breast cancer has long been known to conserve a heterogeneous population of cells. While the majority of cells that make up tumors are destined to differentiate and eventually stop dividing, only minority populations of cells, termed cancer stem cell, possess extensive self renewal capability. These cancer stem cells possess characteristics of both stem cells and cancer cells. Breast cancer stem cells reversal to breast somatic stem cells offer a new therapy, that not only can stop the spread of breast cancer cells, but also can differentiate breast cancer stem cells into normal breast somatic stem cells. These can replace damaged breast tissue. Nevertheless, the complexity of realizing this therapy approach needs further research.

  2. Stem cells and healthy aging.

    PubMed

    Goodell, Margaret A; Rando, Thomas A

    2015-12-04

    Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.

  3. Multipotent Stem Cell and Reproduction.

    PubMed

    Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sobhani, Aligholi

    2016-01-01

    Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. The accessibility and adaptability of these amazing cells create them a great therapeutic choice for different part of medical approaches, and it becomes interesting topic in the scientific researches to found obvious method for the most advantageous use of MSC-based therapies. Recent studies in the field of stem cell biology have provided new perspectives and opportunities for the treatment of infertility disorders.

  4. Stem Cells and Female Reproduction

    PubMed Central

    Du, Hongling; Taylor, Hugh S.

    2011-01-01

    Several recent findings in stem cell biology have resulted in new opportunities for the treatment of reproductive disease. Endometrial regeneration can be driven by bone marrow derived stem cells. This finding has potential implications for the treatment of uterine disorders. It also supports a new theory for the etiology of endometriosis. The ovaries have been shown to contain stem cells that form oocytes in adults and can be cultured in vitro to develop mature oocytes. Stem cells from the fetus have been demonstrated to lead to microchimerism in the mother and implicated in several maternal diseases. Additionally the placenta may be another source of hematopoietic stem cell. Finally endometrial derived stem cells have been demonstrated to differentiate into non-reproductive tissues. While we are just beginning to understand stem cells and many key questions remain, the potential advantages of stem cells in reproductive biology and medicine are apparent. PMID:19208782

  5. Stem Cell Organoid Engineering

    PubMed Central

    Yin, Xiaolei; Mead, Benjamin E.; Safaee, Helia; Langer, Robert; Karp, Jeffrey M.; Levy, Oren

    2016-01-01

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies. PMID:26748754

  6. Engineering Stem Cell Organoids.

    PubMed

    Yin, Xiaolei; Mead, Benjamin E; Safaee, Helia; Langer, Robert; Karp, Jeffrey M; Levy, Oren

    2016-01-07

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies.

  7. Cloning of Mammary Stem Cells

    DTIC Science & Technology

    2001-11-01

    these parity-induced cells do represent a totipotent mammary stem cell population per se, but these cells might support stem cell maintenance as... Stem Cells PRINCIPAL INVESTIGATOR: Dr. Kay-Uwe Wagner CONTRACTING ORGANIZATION: University of Nebraska Medical Center Omaha, Nebraska 68198-6810 REPORT...Mammary Stem Cells DAMD17-00-1-0641 6. AUTHOR(S) Dr. Kay-Uwe Wagner 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT

  8. 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.

  9. Stem Cell Transplants (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Stem Cell Transplants KidsHealth > For Parents > Stem Cell Transplants A A A What's in this article? ... Recovery Coping en español Trasplantes de células madre Stem cells are cells in the body that have the ...

  10. Information on Stem Cell Research

    MedlinePlus

    ... Home » Current Research » Focus on Research Focus on Stem Cell Research Stem cells possess the unique ability to differentiate into many ... they also retain the ability to produce more stem cells, a process termed self-renewal. There are multiple ...

  11. 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…

  12. Multifunctional nanoparticles for protein detections in thin channels.

    PubMed

    Tsai, Hweiyan; Lin, Weimin; Chuang, Mingchieh; Lu, Yishuan; Fuh, C Bor

    2017-04-15

    This paper presents a method for simultaneous detection of two proteins by using multifunctional nanoparticles with a magnetic immunoassay in thin channels. Biofunctional magnetic graphene quantum dots (GQDs) combined with two biofunctional quantum dots (QDs) were used for simultaneously detecting two proteins. Magnetic GQDs enabled selective and quantitative nanoparticle deposition with blue emission. Biofunctional QDs confirmed the two protein detections with orange and green emissions. We used two model biomarkers [alpha-fetoprotein (AFP) and cancer antigen 125 (CA125)] to demonstrate the feasibility of the proposed method. The detection limits (0.06pg/mL AFP and 0.001U/mL CA125) and linear ranges (0.2pg/mL-0.68ng/mL AFP and 0.003-25U/mL CA125) of this method are the same as those of single protein detection within experimental errors. These detection limits are substantially lower and the linear ranges are considerably wider than those of enzyme-linked immunosorbent assay (ELISA) and other immunoassay methods. The differences between the proposed method and an ELISA method in AFP and CA125 measurements of serum samples were less than 12%. The proposed method demonstrates favorable detection of biomarkers with advantages of speed, sensitivity, selectivity, and throughput.

  13. Fetoprotein Derived Short Peptide Coated Nanostructured Amphiphilic Surfaces for Targeting Mouse Breast Cancer Cells

    NASA Astrophysics Data System (ADS)

    Brown, Alexandra M.; Miranda-Alarćon, Yoliem S.; Knoll, Grant A.; Santora, Anthony M.; Banerjee, Ipsita A.

    In this work, self-assembled tumor targeting nanostructured surfaces were developed from a newly designed amphiphile by conjugating boc protected isoleucine with 2,2‧ ethylenedioxy bis ethylamine (IED). To target mouse mammary tumor cells, a short peptide sequence derived from the human alpha-fetoprotein (AFP), LSEDKLLACGEG was attached to the self-assembled nanostructures. Tumor targeting and cell proliferation were examined in the presence of nanoscale assemblies. To further obliterate mouse breast tumor cells, the chemotherapeutic drug tamoxifen was then entrapped into the nanoassemblies. Our studies indicated that the targeting systems were able to efficiently encapsulate and release tamoxifen. Cell proliferation studies showed that IED-AFP peptide loaded with tamoxifen decreased the proliferation of breast cancer cells while in the presence of the IED-AFP peptide nanoassemblies alone, the growth was relatively slower. In the presence of human dermal fibroblasts however cell proliferation continued similar to controls. Furthermore, the nanoscale assemblies were found to induce apoptosis in mouse breast cancer cells. To examine live binding interactions, SPR analysis revealed that tamoxifen encapsulated IED-AFP peptide nanoassemblies bound to the breast cancer cells more efficiently compared to unencapsulated assemblies. Thus, we have developed nanoscale assemblies that can specifically bind to and target tumor cells, with increased toxicity in the presence of a chemotherapeutic drug.

  14. Ultrasensitive Multiplexed Immunoassay for Tumor Biomarkers Based on DNA Hybridization Chain Reaction Amplifying Signal.

    PubMed

    Guo, Jinjin; Wang, Junchun; Zhao, Junqing; Guo, Zilin; Zhang, Yuzhong

    2016-03-23

    In this work, a novel electrochemical immunoassay protocol has been reported for simultaneous determination of multiple tumor biomarkers based on DNA hybridization chain reaction (HCR) for signal amplification. Alpha-fetoprotein (AFP) and prostate specific antigen (PSA) were selected as model biomarkers. The immunoassay protocol contained primary antibodies immobilized on gold nanoparticles (Au NPs), secondary antibodies conjugated with DNA concatemer from HCR of primer, auxiliary probe, and signal probe labeled with signal molecules (methyleneblue (MB) and ferrocene (Fc)). In the presence of target biomarkers, the sandwich immunocomplex was formed between the primary antibodies and secondary antibodies bioconjugates carrying numerous signal molecules. As a result, two well-resolved reduction peaks, one was at -0.35 V (corresponding to MB) and other was at 0.33 V (corresponding to Fc; both vs SCE), were obtained in differential pulse voltammetry, and peak currents changed were related to the level of biomarkers. Under optimal conditions, the electrochemical immunoassay exhibited a wide linear response range (0.5 pg mL(-1) to 50 ng mL(-1)) and low detection limits (PSA, 0.17 pg mL(-1); AFP, 0.25 pg mL(-1)) (at S/N = 3). In addition, the immunoassay was evaluated by analyzing simulate human serum sample, and the recoveries obtained were within 99.4-107.6% for PSA and 97.9-108.2% for AFP, indicating the immnuoassay could be applied to the simultaneous detection of AFP and PSA in human serum samples.

  15. Squamous cell carcinoma antigen in hepatocellular carcinoma: Ready for the prime time?

    PubMed

    Montagnana, Martina; Danese, Elisa; Lippi, Giuseppe

    2015-05-20

    Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the third cause of cancer deaths. The leading predisposing condition is represented by an underlying viral hepatitis, mainly sustained by hepatitis B and C viruses. Since the cumulative risk of developing HCC can be as high as 30-fold in patients with infectious cirrhosis, a timely diagnosis is necessary for establishing an appropriate treatment in these patients. The armamentarium of diagnostic and prognostic biomarkers in patients with HCC currently entails alpha-fetoprotein (AFP) and a limited number of innovative biomarkers, among which squamous cell carcinoma antigen (SCCA) and its immune complexes are among the most widely investigated. The clinical data published so far and reviewed in this article seemingly suggest that neither total serum SSCA or its isoform 1 (i.e., SCCA1) may be ready for the prime time for management of patients with HCC. More interesting evidence has emerged from studies investigating the serum values of SCCA-IgM, since the diagnostic performance of this biomarker was found to be frequently superior to that of AFP and, even more importantly, the combination of SCCA-IgM and AFP was characterized by a much better sensitivity than either biomarker alone, with only a modest decrease of specificity. Larger studies are needed before these preliminary findings can be generalized, but the combined use of AFP and SCCA-IgM represents an appealing perspective in diagnosis and prognostication of HCC.

  16. 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.

  17. One-step synthesis of redox-active polymer/AU nanocomposites for electrochemical immunoassay of multiplexed tumor markers.

    PubMed

    Liu, Zhimin; Rong, Qinfeng; Ma, Zhanfang; Han, Hongliang

    2015-03-15

    In this work, a simple and sensitive multiplexed immunoassay protocol for simultaneous electrochemical determination of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) was designed using redox-active nanocomposites. As the redox-active species, the poly(o-phenylenediamine) (POPD)/Au nanocomposite and poly(vinyl ferrocene-2-aminothiophenol) (poly(VFc-ATP))/Au nanocomposite were obtained by one-step method which HAuCl4 was used as the oxidant. With Au nanoparticles (AuNPs), the nanocomposites were successful to immobilize labeled anti-CEA and anti-AFP as the immunosensing probes. The proposed electrochemical immunoassay enabled the simultaneous monitoring of AFP and CEA in a wide range of 0.01-100ngmL(-1). The detection limits was 0.006ngmL(-1) for CEA and 0.003ngmL(-1) for AFP (S/N=3). The assay results of serum samples with the proposed method were well consistent with the reference values from standard ELISA method. And the negligible cross-reactivity between the two analytes makes it possesses potential promise in clinical diagnosis.

  18. Immunohistochemical study of pancreatoblastoma.

    PubMed

    Ohaki, Y; Misugi, K; Fukuda, J; Okudaira, M; Hirose, M

    1987-10-01

    Three cases of pancreatoblastoma in children were examined immunohistochemically and the results were compared with those of pancreatic duct carcinoma in adults. The pancreatoblastoma demonstrated positive reactions to alpha-fetoprotein (AFP) (67%: 2/3), alpha-1-antitrypsin (AAT) (100%: 3/3), carcinoembryonic antigen (CEA) (67%: 2/3) and keratin (33%: 1/3), although CEA was only weakly positive in both cases. On the other hand, adult pancreatic duct carcinoma showed positive reactions as follows; AFP: 3% (1/29), AAT: 21% (6/29), CEA: 97% (28/29) and keratin: 93% (27/29). Also, endocrine substances including insulin, glucagon and somatostatin were all negative in the pancreatoblastomas. Two cases of pancreatoblastoma which were immunohistochemically positive for AFP also showed elevation of the serum AFP level clinically. The different expressive pattern of oncofetal antigens in pancreatoblastoma as compared with pancreatic duct carcinoma in adults may provide further supporting evidence for the embryonic nature of pancreatoblastoma, and suggests that such a pattern might be used as a tumor marker for pancreatoblastoma.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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…

  4. "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…

  5. 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,…

  6. 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…

  7. STEM Comes to Preschool

    ERIC Educational Resources Information Center

    Moomaw, Sally; Davis, Jaumall A.

    2010-01-01

    Math and science and the related technology and engineering are natural pairings. These four disciplines form the acronym STEM (Science, Technology, Engineering, and Math) and can be readily combined into an integrated curriculum for early childhood classrooms. Many educators believe that children learn best when disciplines are interconnected. An…

  8. Advancing Diversity in STEM

    ERIC Educational Resources Information Center

    Hill, Paul L.; Shaw, Rose A.; Taylor, Jan R.; Hallar, Brittan L.

    2011-01-01

    Although progress has been made, greater efforts are needed to promote faculty diversity at the college and university levels, especially in STEM fields. Thus, it is important to elucidate best practices both for increasing awareness of diversity issues pertaining to higher education and for implementing change. This article focuses on the…

  9. 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…

  10. 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…

  11. Convenient and efficient enrichment of the CD133+ liver cells from rat fetal liver cells as a source of liver stem/progenitor cells.

    PubMed

    Liu, Wei-hui; Li, Ren; Dou, Ke-feng

    2011-03-01

    Although the stem cells are commonly isolated by FACS or MACS, they are very expensive and these is no specific marker for liver stem/progentior cells (LSPCs). This paper applied a convenient and efficient method to enrich LSPCs. The fetal liver cells (FLCs) were firstly enriched by Percoll discontinuous gradient centrifugation (PDGC) from the rat fetal liver. Then the FLCs in culture were purified to be homogeneous in size by differential trypsinization and differential adherence (DTDA). Flow cytometric analysis revealed more than half of the purified FLCs expressed alternative markers of LSPCs (CD117, c-Met, Sca-1, CD90, CD49f and CD133). In other words, the purified FLCs were heterogeneous. Therefore, they were sequentially layered into six fractions by Percoll continuous gradient centrifugation (PCGC). Both CD133 and CD49f expressed decreasingly from fraction 1 to 6. In fraction 1 and 2, about 85% FLCs expressed CD133, which were revealed to be LSPCs by high expressions of AFP and CK-19, low expressions of G-6-P and ALB. To conclude, the purity of CD133(+) LSPCs enriched by combination of PDGC, DTDA and PCGC is close to that obtained by MACS. This study will greatly contribute to two important biological aspects: liver stem cells isolation and liver cell therapy.

  12. Stem cell mobilization.

    PubMed

    Cottler-Fox, Michele H; Lapidot, Tsvee; Petit, Isabelle; Kollet, Orit; DiPersio, John F; Link, Dan; Devine, Steven

    2003-01-01

    Successful blood and marrow transplant (BMT), both autologous and allogeneic, requires the infusion of a sufficient number of hematopoietic progenitor/stem cells (HPCs) capable of homing to the marrow cavity and regenerating a full array of hematopoietic cell lineages in a timely fashion. At present, the most commonly used surrogate marker for HPCs is the cell surface marker CD34, identified in the clinical laboratory by flow cytometry. Clinical studies have shown that infusion of at least 2 x 10(6) CD34(+) cells/kg recipient body weight results in reliable engraftment as measured by recovery of adequate neutrophil and platelet counts approximately 14 days after transplant. Recruitment of HPCs from the marrow into the blood is termed mobilization, or, more commonly, stem cell mobilization. In Section I, Dr. Tsvee Lapidot and colleagues review the wide range of factors influencing stem cell mobilization. Our current understanding focuses on chemokines, proteolytic enzymes, adhesion molecules, cytokines and stromal cell-stem cell interactions. On the basis of this understanding, new approaches to mobilization have been designed and are now starting to undergo clinical testing. In Section II, Dr. Michele Cottler-Fox describes factors predicting the ability to mobilize the older patient with myeloma. In addition, clinical approaches to improving collection by individualizing the timing of apheresis and adjusting the volume of blood processed to achieve a desired product are discussed. Key to this process is the daily enumeration of blood CD34(+) cells. Newer methods of enumerating and mobilizing autologous blood HPCs are discussed. In Section III, Dr. John DiPersio and colleagues provide data on clinical results of mobilizing allogeneic donors with G-CSF, GM-CSF and the combination of both as relates to the number and type of cells collected by apheresis. Newer methods of stem cell mobilization as well as the relationship of graft composition on immune reconstitution

  13. Inflammation and cancer stem cells.

    PubMed

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei

    2014-04-10

    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche.

  14. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    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.

  15. 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.

  16. 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

  17. Stem cells and transplant arteriosclerosis.

    PubMed

    Xu, Qingbo

    2008-05-09

    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.

  18. 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

  19. Neural stem cells: an overview.

    PubMed

    Parati, E A; Pozzi, S; Ottolina, A; Onofrj, M; Bez, A; Pagano, S F

    2004-01-01

    Multipotent stem cells are present in the majority of mammalian tissues where they are a renewable source of specialized cells. According to the several biological portions from which multipotent stem cells can be derived, they are characterized as a) embryonic stem cells (ESCs) isolated from the pluripotent inner-cell mass of the pre-implantation blastocyste-stage embryo; b) multipotent fetal stem cells (FSCs) from aborted fetuses; and c) adult stem cells (ASCs) localized in small zones of several organs known as "niche" where a subset of tissue cells and extracellular substrates can indefinitely house one or more stem cells and control their self-renewal and progeny production in vivo. ECSs have an high self-renewing capacity, plasticity and pluripotency over the years. Pluripotency is a property that makes a stem cell able to give rise to all cell type found in the embryo and adult animals.

  20. 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.

  1. The changing role of surgery in the treatment of primary liver cancer.

    PubMed

    Tang, Z Y; Yu, Y Q; Zhou, X D

    1986-01-01

    For decades, the role of surgery in the treatment of primary liver cancer (PLC) was important but limited. However, a comparison of pathologically proven PLC during the three periods 1958-1966, 1967-1975, and 1976-1984 revealed that as a result of alpha fetoprotein (AFP) serosurvey, changing concepts in surgical oncology, and introduction of new surgical modalities, the role of surgery has become greater. The increasing proportion of subclinical PLC (0, 7.2, and 21.2%) has favored the increasing series resection rate (16.1, 34.7, and 39.6%) and palliative surgery (13.7, 17.0, and 29.8%). The results indicated that early resection, reoperation for subclinical recurrence, resection of huge PLC in stages, and combination of palliative surgery other than resection might be responsible for the increasing 5-year survival rate (1.7, 7.1, and 19.5%) in the entire series.

  2. Self-healing encapsulation strategy for preparing highly stable, functionalized quantum-dot barcodes.

    PubMed

    Song, Tao; Liu, Junqing; Li, Wenbin; Li, Yunhong; Yang, Qiuhua; Gong, Xiaoqun; Xuan, Lixue; Chang, Jin

    2014-02-26

    Quantum dot (QD) barcodes are becoming an urgent requirement for researchers and clinicians to obtain high-density information in multiplexed suspension (bead-based) assay. However, how to improve the stability of quantum dot barcodes is a longstanding issue. Here, we present a new self-healing encapsulation strategy to generate functionalized uniform quantum dots barcodes with high physical and chemical stability. This efficient and facile strategy could make porous polymer microspheres self-heal to encapsulate QDs via the thermal motion and interaction of the molecular chains. Consequently, the new strategy solved especially the QDs leakage problem and improved the chemical stability under different pH physiological conditions as well as the longtime storage stability. In the meantime, the encoding capacity and the spatial distribution uniformity of quantum dots could be also improved. Furthermore, immunofluorescence assays for alpha fetoprotein (AFP) detections indicated that carboxyl groups on the surface of QD-encoded microspheres could facilitate efficient attachment of biomacromolecules.

  3. Ultrathin gold nanowire-functionalized carbon nanotubes for hybrid molecular sensing.

    PubMed

    Cui, Huizhong; Hong, Chenglin; Ying, Andrew; Yang, Xinmai; Ren, Shenqiang

    2013-09-24

    Carbon nanotubes (CNTs) have shown great potential as sensing component in the electrochemical field effect transistor and optical sensors, because of their extraordinary one-dimensional electronic structure, thermal conductivity, and tunable and stable near-infrared emission. However, the insolubility of CNTs due to strong van der Waals interactions limits their use in the field of nanotechnology. In this study, we demonstrate that noncovalent ultrathin gold nanowires functionalized multiwalled carbon nanotube (GNW-CNT) hybrid sensing agents show highly efficient and selective immune molecular sensing in electrochemical and near-infrared photoacoustic imaging methods. A detection limit of 0.01 ng/mL for the alpha-fetoprotein (AFP) antigen with high selectivity is shown. The extraordinary optical absorption, thermal, and electric conductivity of hybrid GNW-CNTs presented in this study could be an effective tactic to integrate imaging, sensing, and treatment functionalities.

  4. 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.

  5. Lipoprotein-X and other tests in the diagnosis of obstructive jaundice in the infant.

    PubMed

    Lipsitz, P J; Yoss, B; Schussheim, A

    1979-01-01

    The infant with elevated direct-reacting bilirubin levels requires an early specific diagnosis to identify those who would require early surgical intervention and those in whom the bilirubin levels will eventually return to normal. This study compares the accuracy of three tests: the serum lipoprotein-X (LP-X), the I131 rose bengal (IRB) excretion and the serum alpha-fetoprotein (AFP) in making a specific diagnosis in 15 patients. When used individually the accuracy of the tests varies from 56-100%. The LP-X and IRB excretion are more specific and when in agreement are 100% acurate in the diagnosis of the neonatal hepatitis syndrome (NHS) or extrahepatic biliary obstruction (EHBO). This study suggests that both the LP-X and IRB excretion should be used in the investigation of the infant with conjugated hyperbilirubinemia.

  6. Combined hepatocellular-cholangiocarcinoma with stem cell features, ductal plate malformation subtype: a case report and proposal of a new subtype.

    PubMed

    Terada, Tadashi

    2013-01-01

    In the current WHO blue book, combined hepatocellular-cholangiocarcinoma (C-HCC-CC) was classified into two types; classical type and type with stem cell features. The latter is extremely rare, and is subcategorized into the following three subtypes; typical subtype, intermediate cell subtype, and cholangiocellular subtype. Recently, intrahepatic cholangiocarcinoma (ICC) with features of ductal plate malformations (DPM) have been reported, and the ICC with DPM was proposed as a subtype of ICC. The author herein reports a case of C-HCC-CC with stem cell features. Characteristically, the CC element showed features of DPM. A 51-year-old man of HBV carrier was found to have high AFP. A laboratory test showed an elevated AFP (395 ng/ml, normal 9-10) and hepatitis B virus-related antigens and antibodies. Liver and ductal enzymes and PIVKAII were within normal ranges. Imaging modalities including CT identified a small liver tumor. Hepatocellular carcinoma (HCC) was suspected, and the resection of the hepatic tumor was performed. Grossly, the liver tumor is well-defined white solid tumor measuring 22x16x23 mm. Microscopically, the tumor was a C-HCC-CC, and was composed of following three elements: well differentiated HCC, well differentiated cholangiocarcinoma (CC), and intermediate tumor element. Characteristically, the CC cells formed tortuous markedly irregular tubules with intraluminal cell projections, bridge formations, intraluminal tumor biliary cells; such features very resembled the ductal plate (DP) and DPM. Immunohistochemically, the cells of CC element were positive for stem cell antigens (KIT (CD117), CD56, EMA, CD34), HepPar1, EpCAM, cytokeratin (CK) CAM5.2, AE1/3, CK34BE12 (focal), CK7, CK8, CK18, CK19, CA19-9, p53, MUC1, MUC2, MUC5AC, MUC6, and Ki-67 (labeling=25%). They were negative for CEA, CK5/6, CK20, NSE, chromogranin, synaptophysin, and p63. No mucins were found by histochemically. The background liver showed chronic hepatitis B (a1, f3). Very

  7. [Stem cell colloquy: conclusion].

    PubMed

    Tubiana, Maurice

    2002-10-01

    The stem cell data presented and discussed during the symposium raise the hope that important medical progress can be made in several fields: neuro-degenerative diseases, those linked to cellular deficit, some aspects of aging linked to cellular degeneration, and the treatment of cancers that may harm normal tissues at risk of being infiltrated by malignant cells. Three main types of stem cells are available. (i) Those present in normal adult tissue: contrary to what was believed, some data suggest that certain adult stem cells have a great plasticity (they can differentiate into cells different from those in tissues from which they were taken) and can proliferate in vitro without losing their properties. Nevertheless, their use faces several obstacles: in ill or elderly subjects, then these cells can be limited in number or not multiply well in vitro. In this case, auto-grafting of the cells cannot be used. They must be sought in another subject, and allo-grafting causes difficult and sometimes insoluble problems of immunological tolerance. (ii) Embryonic stem cells from surplus human embryos, obtained by in vitro fertilisation, which the parents decide not to use: these cells have a great potential for proliferation and differentiation, but can also encounter problems of immunological intolerance. (iii) Cells obtained from cell nuclear transfer in oocytes: these cells are well tolerated, since they are genetically and immunologically identical to those of the host. All types of stem cells can be obtained with them. However, they do present problems. For obtaining them, female oocytes are needed, which could lead to their commercialization. Moreover, the first steps for obtaining these cells are identical to those used in reproductive cloning. It therefore appears that each type of cell raises difficult scientific and practical problems. More research is needed to overcome these obstacles and to determine which type of stem cell constitutes the best solution for

  8. 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

  9. 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,…

  10. Stem cells in dentistry--part I: stem cell sources.

    PubMed

    Egusa, Hiroshi; Sonoyama, Wataru; Nishimura, Masahiro; Atsuta, Ikiru; Akiyama, Kentaro

    2012-07-01

    Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral and maxillofacial tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (iPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. Part I of this review outlines various types of intra- and extra-oral tissue-derived stem cells with regard to clinical availability and applications in dentistry. Additionally, appropriate sources of stem cells for regenerative dentistry are discussed with regard to differentiation capacity, accessibility and possible immunomodulatory properties.

  11. Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study.

    PubMed

    Wang, Dandan; Niu, Lingying; Feng, Xuebing; Yuan, Xinran; Zhao, Shengnan; Zhang, Huayong; Liang, Jun; Zhao, Cheng; Wang, Hong; Hua, Bingzhu; Sun, Lingyun

    2016-06-07

    The aim of this study is to assess the long-term safety of allogeneic umbilical cord mesenchymal stem cells (UC MSCs) transplantation for patients with refractory systemic lupus erythematosus (SLE). Nine SLE patients, who were refractory to steroid and immunosuppressive drugs treatment and underwent MSCs transplantation in 2009, were enrolled. One million allogeneic UC MSCs per kilogram of body weight were infused intravenously at days 0 and 7. The possible adverse events, including immediately after MSCs infusions, as well as the long-term safety profiles were observed. Blood and urine routine test, liver function, electrocardiogram, chest radiography and serum levels of tumor markers, including alpha fetal protein (AFP), cancer embryo antigen (CEA), carbohydrate antigen 155 (CA155) and CA199, were assayed before and 1, 2, 4 and 6 years after MSCs transplantation. All the patients completed two times of MSCs infusions. One patient had mild dizzy and warm sensation 5 min after MSCs infusion, and the symptoms disappeared quickly. No other adverse event, including fluster, headache, nausea or vomit, was observed. There was no change in peripheral white blood cell count, red blood cell count and platelet number in these patients after followed up for 6 years. Liver functional analysis showed that serum alanine aminotransferase, glutamic-oxalacetic transaminase, total bilirubin and direct bilirubin remained in normal range after MSCs infusions. No newly onset abnormality was detected on electrocardiogram and chest radiography. Moreover, we found no rise of serum tumor markers, including AFP, CEA, CA125 and CA199, before and 6 years after MSCs infusions. Our long-term observational study demonstrated a good safety profile of allogeneic UC MSCs in SLE patients.

  12. Measuring stem cell circadian rhythm.

    PubMed

    Hrushesky, William; Rich, Ivan N

    2015-01-01

    Circadian rhythms are biological rhythms that occur within a 24-h time cycle. Sleep is a prime example of a circadian rhythm and with it melatonin production. Stem cell systems also demonstrate circadian rhythms. This is particularly the case for the proliferating cells within the system. In fact, all proliferating cell populations exhibit their own circadian rhythm, which has important implications for disease and the treatment of disease. Stem cell chronobiology is particularly important because the treatment of cancer can be significantly affected by the time of day a drug is administered. This protocol provides a basis for measuring hematopoietic stem cell circadian rhythm for future stem cell chronotherapeutic applications.

  13. 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.

  14. 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

  15. 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…

  16. Learning for STEM Literacy: STEM Literacy for Learning

    ERIC Educational Resources Information Center

    Zollman, Alan

    2012-01-01

    We are in the STEM generation whose comprehensive purpose is to resolve (1) societal needs for new technological and scientific advances; (2) economic needs for national security; and (3) personal needs to become a fulfilled, productive, knowledgeable citizen. STEM specifically refers to science, technology, engineering, and mathematics, but now…

  17. Aging, metabolism and stem cells: Spotlight on muscle stem cells.

    PubMed

    García-Prat, Laura; Muñoz-Cánoves, Pura

    2017-04-15

    All tissues and organs undergo a progressive regenerative decline as they age. This decline has been mainly attributed to loss of stem cell number and/or function, and both stem cell-intrinsic changes and alterations in local niches and/or systemic environment over time are known to contribute to the stem cell aging phenotype. Advancing in the molecular understanding of the deterioration of stem cell cells with aging is key for targeting the specific causes of tissue regenerative dysfunction at advanced stages of life. Here, we revise exciting recent findings on why stem cells age and the consequences on tissue regeneration, with a special focus on regeneration of skeletal muscle. We also highlight newly identified common molecular pathways affecting diverse types of aging stem cells, such as altered proteostasis, metabolism, or senescence entry, and discuss the questions raised by these findings. Finally, we comment on emerging stem cell rejuvenation strategies, principally emanating from studies on muscle stem cells, which will surely burst tissue regeneration research for future benefit of the increasing human aging population.

  18. 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

  19. STEM TIPS: Supporting the Beginning Secondary STEM Teacher

    ERIC Educational Resources Information Center

    Jones, Griff; Dana, Thomas; LaFramenta, Joanne; Adams, Thomasenia Lott; Arnold, Jason Dean

    2016-01-01

    The STEM TIPS mobile-ready support platform gives institutions or school districts the ability to provide immediate and customized mentoring to teachers through multiple tiers of web-based support and resources. Using the results of a needs assessment, STEM TIPS was created and launched in partnership with 18 Florida school districts. Further…

  20. 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…

  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. 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

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. 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...

  12. 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…

  13. Ethical Reasoning in STEM Disciplines

    ERIC Educational Resources Information Center

    Tekerek, Mehmet; Karakaya, Ferhat; Tekerek, Betül

    2016-01-01

    In this study, it was aimed to determine ethical reasoning of lecturers in STEM disciplines in terms of several independent variables (gender, working another institution, age, academic title, academic discipline, service period). This study was designed as a survey research. Lecturers in STEM disciplines in Kahramanmaras Sutçuimam University were…

  14. 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…

  15. Stem cell mitochondria during aging.

    PubMed

    Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Shyh-Chang, Ng

    2016-04-01

    Mitochondria are the central hubs of cellular metabolism, equipped with their own mitochondrial DNA (mtDNA) blueprints to direct part of the programming of mitochondrial oxidative metabolism and thus reactive oxygen species (ROS) levels. In stem cells, many stem cell factors governing the intricate balance between self-renewal and differentiation have been found to directly regulate mitochondrial processes to control stem cell behaviors during tissue regeneration and aging. Moreover, numerous nutrient-sensitive signaling pathways controlling organismal longevity in an evolutionarily conserved fashion also influence stem cell-mediated tissue homeostasis during aging via regulation of stem cell mitochondria. At the genomic level, it has been demonstrated that heritable mtDNA mutations and variants affect mammalian stem cell homeostasis and influence the risk for human degenerative diseases during aging. Because such a multitude of stem cell factors and signaling pathways ultimately converge on the mitochondria as the primary mechanism to modulate cellular and organismal longevity, it would be most efficacious to develop technologies to therapeutically target and direct mitochondrial repair in stem cells, as a unified strategy to combat aging-related degenerative diseases in the future.

  16. 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…

  17. 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

  18. (Re)defining stem cells.

    PubMed

    Shostak, Stanley

    2006-03-01

    Stem-cell nomenclature is in a muddle! So-called stem cells may be self-renewing or emergent, oligopotent (uni- and multipotent) or pluri- and totipotent, cells with perpetual embryonic features or cells that have changed irreversibly. Ambiguity probably seeped into stem cells from common usage, flukes in biology's history beginning with Weismann's divide between germ and soma and Haeckel's biogenic law and ending with contemporary issues over the therapeutic efficacy of adult versus embryonic cells. Confusion centers on tissue dynamics, whether stem cells are properly members of emerging or steady-state populations. Clarity might yet be achieved by codifying differences between cells in emergent populations, including embryonic stem and embryonic germ (ES and EG) cells in tissue culture as opposed to self-renewing (SR) cells in steady-state populations.

  19. Stem cells for spine surgery

    PubMed Central

    Schroeder, Joshua; Kueper, Janina; Leon, Kaplan; Liebergall, Meir

    2015-01-01

    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. PMID:25621119

  20. Stem Cells behind the Barrier

    PubMed Central

    Cangkrama, Michael; Ting, Stephen B.; Darido, Charbel

    2013-01-01

    Epidermal stem cells sustain the adult skin for a lifetime through self-renewal and the production of committed progenitors. These stem cells generate progeny that will undergo terminal differentiation leading to the development of a protective epidermal barrier. Whereas the molecular mechanisms that govern epidermal barrier repair and renewal have been extensively studied, pathways controlling stem cell differentiation remain poorly understood. Asymmetric cell divisions, small non-coding RNAs (microRNAs), chromatin remodeling complexes, and multiple differentiation factors tightly control the balance of stem and progenitor cell proliferation and differentiation, and disruption of this balance leads to skin diseases. In this review, we summarize and discuss current advances in our understanding of the mechanisms regulating epidermal stem and progenitor cell differentiation, and explore new relationships for maintenance of skin barrier function. PMID:23812084

  1. Lasers, stem cells, and COPD

    PubMed Central

    2010-01-01

    The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed. PMID:20158898

  2. 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.

  3. 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.

  4. Expression pattern of pluripotent markers in different embryonic developmental stages of buffalo (Bubalus bubalis) embryos and putative embryonic stem cells generated by parthenogenetic activation.

    PubMed

    Singh, Karn P; Kaushik, Ramakant; Garg, Veena; Sharma, Ruchi; George, Aman; Singh, Manoj K; Manik, Radhey S; Palta, Prabhat; Singla, Suresh K; Chauhan, Manmohan S

    2012-12-01

    In this study, we describe the production of buffalo parthenogenetic blastocysts and subsequent isolation of parthenogenetic embryonic stem cell (PGESC)-like cells. PGESC colonies exhibited dome-shaped morphology and were clearly distinguishable from the feeder layer cells. Different stages of development of parthenogenetic embryos and derived embryonic stem cell (ESC)-like cells expressed key ESC-specific markers, including OCT-4, NANOG, SOX-2, FOXD3, REX-1, STAT-3, TELOMERASE, NUCLEOSTEMIN, and cMYC. Immunofluorescence-based studies revealed that the PGESCs were positive for surface-based pluripotent markers, viz., SSEA-3, SSEA-4, TRA 1-80, TRA 1-60, CD-9, and CD-90 and exhibited high alkaline phosphatase (ALP) activity. PGEC cell-like cells formed embryoid body (EB)-like structures in hanging drop cultures and when cultured for extended period of time spontaneously differentiated into derivatives of three embryonic germ layers as confirmed by RT-PCR for ectodermal (CYTOKERATIN8, NF-68), mesodermal (MSX1, BMP-4, ASA), and endodermal markers (AFP, HNF-4, GATA-4). Differentiation of PGESCs toward the neuronal lineage was successfully directed by supplementation of serum-containing media with retinoic acid. Our results indicate that the isolated ESC-like cells from parthenogenetic blastocyst hold properties of ESCs and express markers of pluripotency. The pluripotency markers were also expressed by early cleavage-stage of buffalo embryos.

  5. Comparison of the clinical features and hematopoietic stem cell transplantation outcomes of mediastinal malignant germ cell tumors with nonmediastinal extragonadal placements

    PubMed Central

    Ocal, Nesrin; Yildiz, Birol; Karadurmus, Nuri; Dogan, Deniz; Ozaydin, Sukru; Ocal, Ramazan; Ozturk, Mustafa; Arpaci, Fikret; Bilgic, Hayati

    2016-01-01

    Objective Even though the primary mediastinal extragonadal germ cell tumors (EGCTs) are rare, they are noteworthy in the differential diagnosis of mediastinal masses. In this study, we aimed to identify the clinical features of mediastinal malignant GCTs and compare the results of hematopoietic stem cell transplantation between mediastinal and nonmediastinal malignant EGCTs. Method Data of the patients with EGCT who were treated and underwent hematopoietic stem cell transplantation at our hospital between 1988 and 2015 were retrieved retrospectively. Results were compared between mediastinal and nonmediastinal EGCTs. Results Data of 65 patients diagnosed with EGCT (37 [56.92%] cases with mediastinal EGCT and 28 [43.07%] cases with nonmediastinal EGCT) were assessed. The clinical stages, frequency of pretransplant status, mean pretransplant time, and mean number of chemotherapy lines before hematopoietic stem cell transplantation were not significantly different between groups. Although the overall survival did not significantly differ between groups, the 5-year survival was significantly higher in mediastinal EGCTs (P=0.02). Yolk sac tumor was significantly more common in mediastinal EGCTs (P=0.05). Mortality rates were higher in seminomas and yolk sac tumors in all cases, higher in embryonal carcinomas in mediastinal EGCT group and higher in yolk sac tumors in nonmediastinal EGCT group. While choriocarcinomas had more aggressive courses in mediastinal EGCTs, seminomas and yolk sac tumors had poorer prognosis in nonmediastinal EGCTs. Short pretransplant time and persistence of elevated posttransplant βhCG and AFP levels were the significant mortality risk factors both in mediastinal and nonmediastinal EGCTs. Conclusion Mediastinal placement of EGCT was not a poor prognostic factor; furthermore, the 5-year survival was significantly higher in mediastinal EGCTs. According to our knowledge, this is the first study that compares the clinical outcomes of hematopoietic

  6. 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…

  7. The Federal Science, Technology, Engineering, and Mathematics (STEM) Education Portfolio. A Report from the Federal Inventory of STEM Education Fast-Track Action Committee, Committee on STEM Education

    DTIC Science & Technology

    2011-12-01

    majors, complete STEM credentials or degree programs, or are prepared to enter STEM careers or advanced education. • STEM Careers : Prepare people to...students who enroll in STEM majors, complete STEM credentials or degree programs, or are prepared to enter STEM careers or advanced education. • STEM... Careers : Prepare people to enter STEM workforce with training or certification (where STEM discipline specific knowledge and skills are the primary

  8. Discovering potential serological biomarker for chronic Hepatitis B Virus-related hepatocellular carcinoma in Chinese population by MAL-associated serum glycoproteomics analysis

    PubMed Central

    Liu, Tianhua; Liu, Denghe; Liu, Riqiang; Jiang, Hucong; Yan, Guoquan; Li, Wei; Sun, Lu; Zhang, Shu; Liu, Yinkun; Guo, Kun

    2017-01-01

    The accuracy of current biomarkers for the diagnosis of hepatocellular carcinoma (HCC), especially chronic Hepatitis B Virus (HBV)-related HCC, is limited. Recent progress in glycoproteomics has provided a novel platform for screening novel serological biomarkers of HCC. In this study, lectin affinity chromatography by Maackia amurensis lectin (MAL) and iTRAQ combined with mass spectrometric analysis were performed to enrich and identify the glycoprotein fractions in serum samples from HBV-related HCC patients and from healthy controls. Seventeen differential MAL-associated glycoproteins were identified. Among them, Galectin 3 binding protein (Gal-3BP) was selected for further evaluated by ELISA analysis and showed a high diagnostic potential of HBV-related HCC, with the AUC of 0.898 and a sensitivity, specificity and accuracy of 80.00%, 93.75% and 86.88%, respectively. Moreover, we constructed a predictive model through the combined use of serum Gal-3BP and Alpha Fetoprotein (AFP), which improved the sensitivity (from 87.5% to 95%), specificity (from 93.75% to 95%) and accuracy (from 90.63% to 95%) of diagnosing early HCC. These data suggested serum Gal-3BP level is a promising biomarker to identify HBV-related HCC and the combined use of serum Gal-3BP and AFP improves the diagnostic potential of HBV-HCC compared with AFP alone in current clinical practice. PMID:28079114

  9. HSP72 and gp96 in gastroenterological cancers.

    PubMed

    Wang, Xiaoping; Wang, Qiaoxia; Lin, Huanping; Li, Sanzhong; Sun, Lijun; Yang, Yixin

    2013-02-18

    Heat shock protein 72 (HSP72) and glycoprotein 96 (gp96) are highly expressed in cancer tissues. Recent studies indicate the possible roles of HSP72 and gp96 in the development and progression of gastrointestinal carcinomas but detailed mechanisms are still ambiguous. Human esophageal cancer, gastric cancer, colon cancer and liver cancer are common gastrointestinal malignant carcinomas in the world. The studies indicated that there existed a significant correlation between the expression of HSP72, gp96 and the development and progression of digestive carcinomas. HSP72 and gp96 expression were significantly associated with the presence of tumor infiltration, lymph node and remote metastasis. Interestingly, studies have found that HSP72 chaperoned alpha-fetoprotein (AFP), HBx in hepatocellular carcinoma, and CD44 in colonic carcinomas. The further researches demonstrated that HSP72-AFP or gp96-AFP recombined vaccine could elicit specific anti-tumor immunity. The high-level expression of HSP72 and gp96 may be not only used as diagnostic or prognostic markers for gastrointestinal carcinomas but also as better immunotherapeutic vaccines in the cancers.

  10. Nitric Oxide Synthase Type III Overexpression By Gene Therapy Exerts Antitumoral Activity In Mouse Hepatocellular Carcinoma.

    PubMed

    González, Raúl; De la Rosa, Ángel J; Romero-Brufau, Santiago; Barrera-Pulido, Lydia; Gallardo-Chamizo, Francisco; Pereira, Sheila; Marín, Luís M; Álamo, José M; Rodríguez-Hernández, Ángeles; Padillo, Francisco J; Muntané, Jordi

    2015-08-01

    Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. Hepa 1-6 cells were used for in vitro and in vivo experiments. The first generation adenovirus was designed to overexpress NOS-3 (or GFP) and luciferase cDNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenoviruses were administered through the tail vein two weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-Luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8 activity in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by l-NAME or p53 siRNA. The tail vein infusion of AFP-NOS- 3/RSV-Luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

  11. Personalized Risk Assessment in Never, Light, and Heavy Smokers in a prospective cohort in Taiwan

    PubMed Central

    Wu, Xifeng; Wen, Chi Pang; Ye, Yuanqing; Tsai, MinKwang; Wen, Christopher; Roth, Jack A.; Pu, Xia; Chow, Wong-Ho; Huff, Chad; Cunningham, Sonia; Huang, Maosheng; Wu, Shuanbei; Tsao, Chwen Keng; Gu, Jian; Lippman, Scott M.

    2016-01-01

    The objective of this study was to develop markedly improved risk prediction models for lung cancer using a prospective cohort of 395,875 participants in Taiwan. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). In multivariate Cox regression analysis, age, gender, smoking pack-years, family history of lung cancer, personal cancer history, BMI, lung function test, and serum biomarkers such as carcinoembryonic antigen (CEA), bilirubin, alpha fetoprotein (AFP), and c-reactive protein (CRP) were identified and included in an integrative risk prediction model. The AUC in overall population was 0.851 (95% CI = 0.840–0.862), with never smokers 0.806 (95% CI = 0.790–0.819), light smokers 0.847 (95% CI = 0.824–0.871), and heavy smokers 0.732 (95% CI = 0.708–0.752). By integrating risk factors such as family history of lung cancer, CEA and AFP for light smokers, and lung function test (Maximum Mid-Expiratory Flow, MMEF25–75%), AFP and CEA for never smokers, light and never smokers with cancer risks as high as those within heavy smokers could be identified. The risk model for heavy smokers can allow us to stratify heavy smokers into subgroups with distinct risks, which, if applied to low-dose computed tomography (LDCT) screening, may greatly reduce false positives. PMID:27805040

  12. 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.

  13. Optimal surveillance program for hepatocellular carcinoma - getting ready, but not yet.

    PubMed

    Wong, Grace Lai-Hung

    2015-08-28

    Hepatocellular carcinoma (HCC) secondary to chronic viral hepatitis is a major health problem in Asian-Pacific regions due to the endemics of chronic hepatitis B and C virus infection. HCC surveillance has been recommended to patients who are at risk to develop HCC. Unfortunately, a significant proportion of patients still died in long run due to tumor recurrence. The key components of an optimal surveillance program include an accurate tumor biomarker and optimal surveillance interval. Serum alpha-fetoprotein (AFP), despite of being the most widely used biomarker for HCC surveillance, it was criticized as neither sensitive nor specific. Other HCC biomarkers, including lectin-reactive AFP (AFP-L3), des-gamma carboxyprothrombin, are still under investigations. Recent study showed cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing to be accurate with both sensitivity and specificity close to 90% in detecting HCC in a case-control study. Concerning the optimal surveillance interval, we believe one size does not fit all patients. Accurate risk prediction to assist prognostication with well-validated HCC risk scores would be useful to decide the need for HCC surveillance. These key components of an optimal HCC surveillance program should be further validated at a surveillance setting.

  14. Serum tumor markers.

    PubMed

    Perkins, Greg L; Slater, Evan D; Sanders, Georganne K; Prichard, John G

    2003-09-15

    Monoclonal antibodies are used to detect serum antigens associated with specific malignancies. These tumor markers are most useful for monitoring response to therapy and detecting early relapse. With the exception of prostate-specific antigen (PSA), tumor markers do not have sufficient sensitivity or specificity for use in screening. Cancer antigen (CA) 27.29 most frequently is used to follow response to therapy in patients with metastatic breast cancer. Carcinoembryonic antigen is used to detect relapse of colorectal cancer, and CA 19-9 may be helpful in establishing the nature of pancreatic masses. CA 125 is useful for evaluating pelvic masses in postmenopausal women, monitoring response to therapy in women with ovarian cancer, and detecting recurrence of this malignancy. Alpha-fetoprotein (AFP), a marker for hepatocellular carcinoma, sometimes is used to screen highly selected populations and to assess hepatic masses in patients at particular risk for developing hepatic malignancy. Testing for the beta subunit of human chorionic gonadotropin (beta-hCG) is an integral part of the diagnosis and management of gestational trophoblastic disease. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG also may be useful in evaluating potential origins of poorly differentiated metastatic cancer. PSA is used to screen for prostate cancer, detect recurrence of the malignancy, and evaluate specific syndromes of adenocarcinoma of unknown primary.

  15. 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.

  16. Liver transplantation versus surgical resection for HCC meeting the Milan criteria

    PubMed Central

    Shen, Jun-Yi; Li, Chuan; Wen, Tian-Fu; Yan, Lv-Nan; Li, Bo; Wang, Wen-Tao; Yang, Jia-Yin; Xu, Ming-Qing; Nazar Highness, Tholakkara

    2016-01-01

    Abstract The optimal treatment (liver transplantation [LT] vs surgical resection [SR]) for early-stage hepatocellular carcinoma (HCC) remains controversial. A total of 209 SR patients and 129 LT patients were identified at our institution. After eliminating 27 patients with Child–Pugh C, the data from 209 SR patients and 102 LT patients were analyzed using a propensity score matching (PSM) model. Forty-six pairs were generated. A subgroup analysis was conducted based on the alpha-fetoprotein (AFP) level or platelet count (PLT). A survival analysis was performed using the Kaplan–Meier method. Gender, satellite lesions, and the treatment method were predictors of HCC recurrence. The Ishak score and treatment methods were associated with long-term survival after surgery. Before PSM, LT patients had a better prognosis than those treated by SR. Among HCC patients with childhood A/B cirrhosis, after PSM, SR achieved similar overall survival outcomes compared with LT. LT and SR resulted in comparable long-term survival for patients with or without thrombocytopenia. Patients with an AFP ≥ 400 ng/mL might achieve more survival benefits from LT. Our propensity score model provided evidence that, compared with transplantation, surgical resection could result in comparable long-term survival for resectable early-stage HCC patients, except for the AFP ≥ 400 ng/mL HCC subgroup. Surgical resection might not be a contraindication for early-stage HCC patients with thrombocytopenia due to their similar prognosis after transplantation. PMID:28033289

  17. Blood neutrophil-lymphocyte ratio predicts survival after hepatectomy for hepatocellular carcinoma: A propensity score-based analysis

    PubMed Central

    Yang, Hao-Jie; Guo, Zhe; Yang, Yu-Ting; Jiang, Jing-Hang; Qi, Ya-Peng; Li, Ji-Jia; Li, Le-Qun; Xiang, Bang-De

    2016-01-01

    AIM: To investigate whether an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) can predict poor survival in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 526 patients with HCC who underwent surgery between 2004 and 2011. RESULTS: Preoperative NLR ≥ 2.81 was an independent predictor of poor disease-free survival (DFS, P < 0.001) and overall survival (OS, P = 0.044). Compared with patients who showed a preoperative NLR < 2.81 and postoperative increase, patients who showed preoperative NLR ≥ 2.81 and postoperative decrease had worse survival (DFS, P < 0.001; OS, P < 0.001). Among patients with preoperative NLR ≥ 2.81, survival was significantly higher among those showing a postoperative decrease in NLR than among those showing an increase (DFS, P < 0.001; OS, P < 0.001). When elevated, alpha-fetoprotein (AFP) provided no prognostic information, and so preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS whenever AFP levels are low or high. CONCLUSION: Preoperative NLR ≥ 2.81 may be an indicator of poor DFS and OS in patients with HCC undergoing surgery. Preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS when elevated AFP levels provide no prognostic information. PMID:27275101

  18. Multi-analyte analysis of cytokines that predict outcomes in patients with hepatocellular carcinoma treated with radiotherapy

    PubMed Central

    Cha, Hyejung; Lee, Eun Jung; Seong, Jinsil

    2017-01-01

    AIM To analyze cytokine levels and to identify their association with outcome in patients with hepatocellular carcinoma (HCC) treated with radiotherapy (RT). METHODS Patients with HCC who were treated with RT were eligible for this prospective study. Blood samples were collected before and after RT, and serum cytokine levels including interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α were analyzed. RESULTS Between 2008 and 2009, 51 patients were enrolled in this study. Baseline IL-6 level was high in patients with a history of pre-RT treatment. Median survival was 13.9 mo with alpha-fetoprotein (AFP) as a significant factor (P = 0.020). Median failure-free survival (FFS) for infield, outfield-intrahepatic and extrahepatic failures were 23.3, 11.5 and 12.0 mo, respectively. Sex and baseline IL-6 level were associated with infield FFS, and baseline IL-10 level was correlated with outfield-intrahepatic FFS. For extrahepatic FFS, AFP was significant (P = 0.034). Patients with a baseline IL-6 level of ≥ 9.7 pg/mL showed worse infield FFS (P = 0.005), and this significance was observed only in treatment-non-naïve patients (P = 0.022). CONCLUSION In addition to AFP, cytokines seem useful in predicting infield and outfield-intrahepatic failure. Serum cytokines could be useful biomarkers for predicting RT outcome in HCC. PMID:28373775

  19. Pancreatic cancer stem cells.

    PubMed

    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.

  20. Immune privilege of stem cells.

    PubMed

    Ichiryu, Naoki; Fairchild, Paul J

    2013-01-01

    Immune privilege provides protection to vital tissues or cells of the body when foreign antigens are introduced into these sites. The modern concept of relative immune privilege applies to a variety of tissues and anatomical structures, including the hair follicles and mucosal surfaces. Even sites of chronic inflammation and developing tumors may acquire immune privilege by recruiting immunoregulatory effector cells. Adult stem cells are no exception. For their importance and vitality, many adult stem cell populations are believed to be immune privileged. A preimplantation-stage embryo that derives from a totipotent stem cell (i.e., a fertilized oocyte) must be protected from maternal allo-rejection for successful implantation and development to occur. Embryonic stem cells, laboratory-derived cell lines of preimplantation blastocyst-origin, may, therefore, retain some of the immunological properties of the developing embryo. However, embryonic stem cells and their differentiated tissue derivatives transplanted into a recipient do not necessarily have an ability to subvert immune responses to the extent required to exploit their pluripotency for regenerative medicine. In this review, an extended definition of immune privilege is developed and the capacity of adult and embryonic stem cells to display both relative and acquired immune privilege is discussed. Furthermore, we explore how these intrinsic properties of stem cells may one day be harnessed for therapeutic gain.

  1. GPCRs in Stem Cell Function

    PubMed Central

    DOZE, VAN A.; PEREZ, DIANNE M.

    2013-01-01

    Many tissues of the body cannot only repair themselves, but also self-renew, a property mainly due to stem cells and the various mechanisms that regulate their behavior. Stem cell biology is a relatively new field. While advances are slowly being realized, stem cells possess huge potential to ameliorate disease and counteract the aging process, causing its speculation as the next panacea. Amidst public pressure to advance rapidly to clinical trials, there is a need to understand the biology of stem cells and to support basic research programs. Without a proper comprehension of how cells and tissues are maintained during the adult life span, clinical trials are bound to fail. This review will cover the basic biology of stem cells, the various types of stem cells, their potential function, and the advantages and disadvantages to their use in medicine. We will next cover the role of G-protein coupled receptors in the regulation of stem cells and their potential in future clinical applications. PMID:23415095

  2. Bone morphogenetic protein-9 is a potent growth inhibitor of hepatocellular carcinoma and reduces the liver cancer stem cells population

    PubMed Central

    Jung, Jae Woo; Yoon, So-Mi; Kim, Subin; Jeon, Yun-Hui; Yoon, Byung-Hak; Yang, Su-Geun; Kim, Min Kyoung; Choe, Senyon; Kuo, Mario Meng-Chiang

    2016-01-01

    The biological role of BMP-9 signaling in liver cancer remains dubious. To explore the potential use of BMP-9 signaling for anti-cancer therapy, we used recombinant human BMP-9, which we referred to as MB109, to study the effect on growth of fifteen hepatocellular carcinoma (HCC) cell lines. MB109 effectively inhibits the proliferation of nine HCC cells in vitro. The anti-proliferative effect was found to be induced by turning on p21 signaling, which caused survivin suppression and G0/G1 cell cycle arrest. ID3 was identified to be the mediator of the MB109-induced p21 expression. Blocking the activity of p38 MAPK diminished ID3 and p21 expression, indicating that MB109 signals through a p38 MAPK/ID3/p21 pathway to arrest cell cycle progression. Moreover, prolonged MB109 treatment suppressed the expression of five prominent liver cancer stem cell (LCSC) markers, including CD44, CD90, AFP, GPC3 and ANPEP. Xenograft model confirmed the anti-tumor and LCSC-suppression capability of MB109 in vivo. Contrary to ongoing efforts of suppressing BMP-9 signaling to inhibit angiogenesis of cancer tissue, these results demonstrate an unexpected therapeutic potential of MB109 to stimulate BMP-9 signaling for anti-cancer therapies. PMID:27650540

  3. FAM83D associates with high tumor recurrence after liver transplantation involving expansion of CD44+ carcinoma stem cells

    PubMed Central

    Lin, Binyi; Chen, Tianchi; Zhang, Qijun; Lu, Xiaoxiao; Zheng, Zhiyun; Ding, Jun; Liu, Jinfeng; Yang, Zhe; Geng, Lei; Wu, Liming; Zhou, Lin; Zheng, Shusen

    2016-01-01

    To investigate the potential oncogene promoting recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT), throughput RNA sequencing was performed in a subgroup of HCC patients. The up-regulated FAM83D in HCC tissues was found and further verified in 150 patients by real-time PCR and immunohistochemistry. FAM83D overexpression significantly correlated with high HCC recurrence rate following LT and poor HCC characteristics such as high AFP, poor differentiation. Of cancer stem cells (CSCs) markers, CD44 expression was effectively suppressed when FAM83D was knocked down by siRNA. Meanwhile, the siRNA transfected cells suppressed formation of sphere and ability of self-renew. In a xenograft tumorigenesis model, FAM83D knockdown apparently inhibited tumor growth and metastasis. Microarray assays revealed that FAM83D promotes CD44 expression via activating the MAPK, TGF-β and Hippo signaling pathways. Furthermore, CD44 knockdown presented reverse effect on above signaling pathways, which suggested that FAM83D was a key activator of loop between CD44 and above signaling pathways. In conclusion, FAM83D promotes HCC recurrence by promoting CD44 expression and CD44+ CSCs malignancy. FAM83D provides a novel therapeutic approach against HCC recurrence after LT. PMID:27769048

  4. 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

  5. [Stem cell therapy: an update].

    PubMed

    Coulombel, Laure

    2009-03-01

    Medicine will be faced with a major challenge in coming years, namely how to treat for tissue dysfunction due to disease and aging There are two basic options: drug therapy and cell therapy. Stem cells have been the subject of intense speculation and controversy for several years, as they open up radically new therapeutic possibilities. Classical drugs can only smoothen consequences of tissue dysfunction, whereas cell therapy has the potential to restore tissue function by providing fresh cells. Cell therapy is totally different from organ transplantation, which can only benefit a limited number of patients. The use of the generic term "stem cells" to designate a whole variety of cell types that are present throughout life, is a source of confusion and ambiguity. It will take years of cognitive research to unravel the molecular mechanisms that govern a stem cell's multi- or totipotent status before we can fully exploit this therapeutic tool to the full. The younger a stem cell the greater its potential and, probably, the more durable its benefits, but the use of embryonic stem cells raises ethical issues. The redundancy or equivalence of diferent categories of cells is another source of controversy, yet researchers must be able to study stem cells in all their diversity, as complementary rather than competitive alternatives, in an acceptable ethical and regulatory environment. We briefly describe the three types of stem cells: pluripotent embryonic stem cells, fetal and adult stem cells, and pluripotent reprogrammed adult somatic cells. Only the former two categories have physiological functions: the first gives rise to tissues and organs while the second maintains tissue function during adulthood

  6. 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

  7. 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.

  8. Effect of Antibiotics against Mycoplasma sp. on Human Embryonic Stem Cells Undifferentiated Status, Pluripotency, Cell Viability and Growth

    PubMed Central

    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 PlasmocinTM 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 PlasmocinTM 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 PlasmocinTM 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 PlasmocinTM 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. PMID:23936178

  9. FACS Sorting Mammary Stem Cells.

    PubMed

    Iriondo, Oihana; Rábano, Miriam; Vivanco, María D M

    2015-01-01

    Fluorescent-activated cell sorting (FACS) represents one of the key techniques that have been used to isolate and characterize stem cells, including cells from the mammary gland. A combination of approaches, including recognition of cell surface antigens and different cellular activities, has facilitated the identification of stem cells from the healthy mammary gland and from breast tumors. In this chapter we describe the protocol to use FACS to separate breast cancer stem cells, but most of the general principles discussed could be applied to sort other types of cells.

  10. Bone repair and stem cells.

    PubMed

    Ono, Noriaki; Kronenberg, Henry M

    2016-10-01

    Bones are an important component of vertebrates; they grow explosively in early life and maintain their strength throughout life. Bones also possess amazing capabilities to repair-the bone is like new without a scar after complete repair. In recent years, a substantial progress has been made in our understanding on mammalian bone stem cells. Mouse genetic models are powerful tools to understand the cell lineage, giving us better insights into stem cells that regulate bone growth, maintenance and repair. Recent findings about these stem cells raise new questions that require further investigations.

  11. 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

  12. Tracking stem cells in the cardiovascular system.

    PubMed

    Chemaly, Elie R; Yoneyama, Ryuichi; Frangioni, John V; Hajjar, Roger J

    2005-11-01

    Stem cells are a promising approach to cardiovascular therapeutics. Animal experiments have assessed the fate of injected stem cells through ex vivo methods on sacrificed animals. Approaches are needed for in vivo tracking of stem cells. Various imaging techniques and contrast agents for stem cell tracking will be reviewed.

  13. The STEM Initiative: Constraints and Challenges

    ERIC Educational Resources Information Center

    Herschbach, Dennis R.

    2011-01-01

    There is considerable national interest in STEM initiatives, but yet there is little discussion concerning what STEM means in terms of a curriculum concept to be applied to school programming. This article focuses on STEM as a curriculum concept. First, STEM programming is discussed in terms of separate subjects, correlated and broad fields…

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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…

  2. 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...

  3. 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...

  4. 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...

  5. Dental stem cells and their sources.

    PubMed

    Sedgley, Christine M; Botero, Tatiana M

    2012-07-01

    The search for more accessible mesenchymal stem cells than those found in bone marrow has propelled interest in dental tissues. Human dental stem/progenitor cells (collectively termed dental stem cells [DSCs]) that have been isolated and characterized include dental pulp stem cells, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, periodontal ligament stem cells, and dental follicle progenitor cells. Common characteristics of these cell populations are the capacity for self-renewal and the ability to differentiate into multiple lineages. In vitro and animal studies have shown that DSCs can differentiate into osseous, odontogenic, adipose, endothelial, and neural-like tissues.

  6. 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

  7. Stem cells, tissue engineering and periodontal regeneration.

    PubMed

    Han, J; Menicanin, D; Gronthos, S; Bartold, P M

    2014-06-01

    The aim of this review is to discuss the clinical utility of stem cells in periodontal regeneration by reviewing relevant literature that assesses the periodontal-regenerative potential of stem cells. We consider and describe the main stem cell populations that have been utilized with regard to periodontal regeneration, including bone marrow-derived mesenchymal stem cells and the main dental-derived mesenchymal stem cell populations: periodontal ligament stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla and dental follicle precursor cells. Research into the use of stem cells for tissue regeneration has the potential to significantly influence periodontal treatment strategies in the future.

  8. Stem cell therapy for Parkinson's disease.

    PubMed

    Takahashi, Jun

    2007-06-01

    The aim of stem cell therapy for Parkinson's disease is to reconstruct nigro-striatal neuronal pathways using endogenous neural stem/precursor cells or grafted dopaminergic neurons. As an alternative, transplantation of stem cell-derived dopaminergic neurons into the striatum has been attempted, with the aim of stimulating local synapse formation and/or release of dopamine and cytokines from grafted cells. Candidate stem cells include neural stem/precursor cells, embryonic stem cells and other stem/precursor cells. Among these, embryonic stem cells are pluripotent cells that proliferate extensively, making them a good potential donor source for transplantation. However, tumor formation and ethical issues present major problems for embryonic stem cell therapy. This review describes the current status of stem cell therapy for Parkinson's disease, as well as future research approaches from a clinical perspective.

  9. [Progress in stem cells and regenerative medicine].

    PubMed

    Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

    2015-06-01

    Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

  10. 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.

  11. Neural Stem Cells and Glioblastoma

    PubMed Central

    Rispoli, Rossella; Conti, Carlo; Celli, Paolo; Caroli, Emanuela; Carletti, Sandro

    2014-01-01

    Summary Glioblastoma multiforme represents one of the most common brain cancers with a rather heterogeneous cellular composition, as indicated by the term “multiforme". Recent reports have described the isolation and identification of cancer neural stem cells from human adult glioblastoma multiforme, which possess the capacity to establish, sustain, and expand these tumours, even under the challenging settings posed by serial transplantation experiments. Our study focused on the distribution of neural cancer stem cells inside the tumour. The study is divided into three phases: removal of tumoral specimens in different areas of the tumour (centre, periphery, marginal zone) in an operative room equipped with a 1.5 T scanner; isolation and characterization of neural cancer stem cells from human adult glioblastoma multiforme; identification of neural cancer stem cell distribution inside the tumour. PMID:24750704

  12. On hematopoietic stem cell fate.

    PubMed

    Metcalf, Donald

    2007-06-01

    Multipotential hematopoietic stem cells (HSCs) maintain blood-cell formation throughout life. Here, Metcalf considers the origin and heterogeneity of HSCs, their ability to self-generate, and their commitment to the various hematopoietic lineages.

  13. Childhood Brain Stem Glioma Treatment

    MedlinePlus

    ... before the cancer is diagnosed and continue for months or years. Childhood brain stem gliomas may cause ... after treatment. Some cancer treatments cause side effects months or years after treatment has ended. These are ...

  14. 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.

  15. Stem Cells in the Lung

    PubMed Central

    Liu, Xiaoming; Driskell, Ryan R.; Engelhardt, John F.

    2007-01-01

    The lung is composed of two major anatomically distinct regions—the conducting airways and gas-exchanging airspaces. From a cell biology standpoint, the conducting airways can be further divided into two major compartments, the tracheobronchial and bronchiolar airways, while the alveolar regions of the lung make up the gas-exchanging airspaces. Each of these regions consists of distinct epithelial cell types with unique cellular physiologies and stem cell compartments. This chapter focuses on model systems with which to study stem cells in the adult tracheobronchial airways, also referred to as the proximal airway of the lung. Important in such models is an appreciation for the diversity of stem cell niches in the conducting airways that provide localized environmental signals to both maintain and mobilize stem cells in the setting of airway injury and normal cellular turnover. Because cellular turnover in airways is relatively slow, methods for analysis of stem cells in vivo have required prior injury to the lung. In contrast, ex vivo and in vitro models for analysis of airway stem cells have used genetic markers to track lineage relationships together with reconstitution systems that mimic airway biology. Over the past decades, several widely acceptable methods have been developed and used in the characterization of adult airway stem/ progenitor cells. These include localization of label-retaining cells (LRCs), retroviral tagging of epithelial cells seeded into xenografts, air–liquid interface cultures to track clonal proliferative potential, and multiple transgenic mouse models. This chapter reviews the biologic context and use of these models while providing detailed methods for several of the more broadly useful models for studying adult airway stem/progenitor cell types. PMID:17141060

  16. Targeting prostate cancer stem cells.

    PubMed

    Crea, Francesco; Mathews, Lesley A; Farrar, William L; Hurt, Elaine M

    2009-12-01

    Cancer stem cells are the sub-population of cells present within tumors responsible for tumorigenesis. These cells have unique biological properties including self-renewal and the ability to differentiate. Furthermore, it is thought that these cells are more resistant to conventional chemotherapy and, as a result, are responsible for patient relapse. We will discuss the identification of prostate cancer stem cells, their unique properties and how these cells may be targeted for more efficacious therapies.

  17. 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

  18. Diabetes and Stem Cell Function

    PubMed Central

    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. PMID:26075247

  19. Modeling Stem Cell Myogenic Differentiation

    PubMed Central

    Deshpande, Rajiv S.; Spector, Alexander A.

    2017-01-01

    The process of stem cell myogenesis (transformation into skeletal muscle cells) includes several stages characterized by the expression of certain combinations of myogenic factors. The first part of this process is accompanied by cell division, while the second part is mainly associated with direct differentiation. The mechanical cues are known to enhance stem cell myogenesis, and the paper focuses on the stem cell differentiation under the condition of externally applied strain. The process of stem cell myogenic differentiation is interpreted as the interplay among transcription factors, targeted proteins and strain-generated signaling molecule, and it is described by a kinetic multi-stage model. The model parameters are optimally adjusted by using the available data from the experiment with adipose-derived stem cells subjected to the application of cyclic uniaxial strains of the magnitude of 10%. The modeling results predict the kinetics of the process of myogenic differentiation, including the number of cells in each stage of differentiation and the rates of differentiation from one stage to another for different strains from 4% to 16%. The developed model can help better understand the process of myogenic differentiation and the effects of mechanical cues on stem cell use in muscle therapies. PMID:28106095

  20. 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

  1. 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

  2. Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis

    PubMed Central

    Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

    2017-01-01

    Aims: To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis. Patients and methods: A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated. Results: Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables. Conclusion: In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy. PMID:28261338

  3. Au-ionic liquid functionalized reduced graphene oxide immunosensing platform for simultaneous electrochemical detection of multiple analytes.

    PubMed

    Liu, Na; Ma, Zhanfang

    2014-01-15

    In this work, an Au-ionic liquid functionalized reduced graphene oxide nanocomposite (IL-rGO-Au) was fabricated via the self-assembly of ionic liquid functionalized reduced graphene oxide (IL-rGO) and gold nanoparticles (AuNPs) by electrostatic interaction. The IL-rGO can be synthesized and stabilized by introducing the cations of the amine-terminated ionic liquids (IL-NH2) into the graphene oxide (GO). With the assistance of IL-NH2, AuNPs were uniformly and densely absorbed on the surfaces of the IL-rGO. The proposed IL-rGO-Au nanocomposite can be used as an immunosensing platform because it can not only facilitate the electrons transfer of the electrode surface but also provide a large accessible surface area for the immobilization of abundant antibody. To assess the performance of the IL-rGO-Au nanocomposite, a sandwich-type electrochemical immunosensor was designed for simultaneous multianalyte detection (carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as model analytes). The chitosan (CS) coated prussian blue nanoparticles (PBNPs) or cadmium hexacyanoferrate nanoparticles (CdNPs) and loaded with AuNPs were used as distinguishable signal tags. The resulting immunosensor exhibited high selectivity and sensitivity in simultaneous determination of CEA and AFP in a single run. The linear ranges were from 0.01 to 100 ng mL(-1) for both CEA and AFP. The detection limits reached 0.01 ng mL(-1) for CEA and 0.006 ng mL(-1) for AFP, respectively. No obvious nonspecific adsorption and cross-talk was observed during a series of analyses to detect target analytes. In addition, for the detection of clinical serum samples, it is well consistent with the data determined by the ELISA, indicating that the immunosensor provides a possible application for the simultaneous multianalyte determination of CEA and AFP in clinical diagnostics.

  4. New Insights into Thyroid Stem Cells

    PubMed Central

    Lin, Reigh-Yi

    2009-01-01

    Stem cells exhibit an extraordinary ability for self-renewal. They also give rise to many specialized cells. The potential of stem cells in regenerative medicine, developmental biology, and drug discovery has been well documented. Although advances in stem cell science have raised broad ethical concerns, it is clear that stem cell technology has revolutionized our thinking in modern biology and medicine and provided the basis for understanding many of the mechanisms controlling basic biological processes and disease mechanisms. This review details the nascent field of thyroid stem cell research, exploring the current status of thyroid stem cell differentiation from the perspectives of both developmental biology and cell replacement therapy. It highlights successes to date in the generation of thyroid follicular cells from embryonic stem cells in the laboratory and the identification and characterization of adult stem cells from human thyroid glands and thyroid cancers. Finally, it outlines future challenges with a focus on potential stem cell therapy for thyroid patients. PMID:17727339

  5. [AFP cites Jiefang Ribao on Shanghai abortions].

    PubMed

    1981-04-07

    The leader of a network of illegal abortionists in China's city of Shanghai was recently sentenced to 3 years in a labor camp. The Shanghai Liberation Daily reported today that Gu Xuezhong started his career by finding an abortionist for a young girl he had made pregnant without getting married. Encouraged by his success, he then joined a former convict and an abortionist to mount an operation on a larger scale. 20 unmarried young women resorted to their service, paying an average of 200 yuan (130 dollars) as well as giving many gifts. The Chinese authorities strongly advise against sex relations outside the scope of marriage. Although abortion is theoretically available free of charge, young unmarried girls are still frequently the target of various rough jokes from hospital staff in charge of carrying out abortions, not counting the social reprimand a pregnancy not sanctioned by marriage incurs. The newspaper said it was Shanghai public security officials who had decided to hand down the sentence of 3 years of "re-education through labor." Re-education through labor is always done in a labor camp. The paper did not report however whether Gu's accomplices had been punished.

  6. 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

  7. Stem cells in orthopaedics and fracture healing.

    PubMed

    Alwattar, Basil J; Schwarzkopf, Ran; Kirsch, Thorsten

    2011-01-01

    Stem cell application is a burgeoning field of medicine that is likely to influence the future of orthopaedic surgery. Stem cells are associated with great promise and great controversy. For the orthopaedic surgeon, stem cells may change the way that orthopaedic surgery is practiced and the overall approach of the treatment of musculoskeletal disease. Stem cells may change the field of orthopaedics from a field dominated by surgical replacements and reconstructions to a field of regeneration and prevention. This review will introduce the basic concepts of stem cells pertinent to the orthopaedic surgeon and proceed with a more in depth discussion of current developments in the study of stem cells in fracture healing.

  8. Stem cells in pediatric cardiology.

    PubMed

    Patel, Pranali; Mital, Seema

    2013-10-01

    The ability to reprogram virtually any cell of human origin to behave like embryonic or pluripotent stem cells is a major breakthrough in stem cell biology. Human induced pluripotent stem cells (iPSC) provide a unique opportunity to study "disease in a dish" within a defined genetic and environmental background. Patient-derived iPSCs have been successfully used to model cardiomyopathies, rhythm disorders and vascular disorders. They also provide an exciting opportunity for drug discovery and drug repurposing for disorders with a known molecular basis including childhood onset heart disease, particularly cardiac genetic disorders. The review will discuss their use in drug discovery, efficacy and toxicity studies with emphasis on challenges in pediatric-focused drug discovery. Issues that will need to be addressed in the coming years include development of maturation protocols for iPSC-derived cardiac lineages, use of iPSCs to study not just cardiac but extra-cardiac phenotypes in the same patient, scaling up of stem cell platforms for high-throughput drug screens, translating drug testing results to clinical applications in the paradigm of personalized medicine, and improving both the efficiency and the safety of iPSC-derived lineages for future stem cell therapies.

  9. 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

  10. 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

  11. Germline and Pluripotent Stem Cells.

    PubMed

    Reik, Wolf; Surani, M Azim

    2015-11-02

    Epigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of the totipotent state, which in turn leads to the establishment of pluripotent cells in blastocysts. The latter are the cells from which pluripotent embryonic stem cells are derived and maintained in culture. Following blastocyst implantation, postimplantation epiblast cells develop, which give rise to all somatic cells as well as primordial germ cells, the precursors of sperm and eggs. Pluripotent stem cells in culture can be induced to undergo differentiation into somatic cells and germ cells in culture. Understanding the natural cycles of epigenetic reprogramming that occur in the germline will allow the generation of better and more versatile stem cells for both therapeutic and research purposes.

  12. Immunotargeting of cancer stem cells

    PubMed Central

    Gąbka-Buszek, Agnieszka; Jankowski, Jakub; Mackiewicz, Andrzej

    2015-01-01

    Cancer stem cells (CSCs) represent a distinctive population of tumour cells that control tumour initiation, progression, and maintenance. Their influence is great enough to risk the statement that successful therapeutic strategy must target CSCs in order to eradicate the disease. Because cancer stem cells are highly resistant to chemo- and radiotherapy, new tools to fight against cancer have to be developed. Expression of antigens such as ALDH, CD44, EpCAM, or CD133, which distinguish CSCs from normal cells, together with CSC immunogenicity and relatively low toxicity of immunotherapies, makes immune targeting of CSCs a promising approach for cancer treatment. This review will present immunotherapeutic approaches using dendritic cells, T cells, pluripotent stem cells, and monoclonal antibodies to target and eliminate CSCs. PMID:25691822

  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. Epigenetics in cancer stem cells.

    PubMed

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  15. 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

  16. 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.…

  17. Multipotent Stem Cell and Current Application.

    PubMed

    Sobhani, Aligholi; Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sargolzaei Aval, Fereydoon

    2017-01-01

    Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. Multipotent Stem cells have been applying in treatment of different disorders such as spinal cord injury, bone fracture, autoimmune diseases, rheumatoid arthritis, hematopoietic defects, and fertility preservation.

  18. Ethics and Governance of Stem Cell Banks.

    PubMed

    Chalmers, Donald; Rathjen, Peter; Rathjen, Joy; Nicol, Dianne

    2017-01-01

    This chapter examines the ethical principles and governance frameworks for stem cell banks. Good governance of stem cell banks should balance facilitation of the clinical use of stem cells with the proper respect and protection of stem cell sample providers and stem cell recipients and ensure compliance with national regulatory requirements to foster public trust in the use of stem cell technology. Stem cell banks must develop with regard to the science, the needs of scientists, and the requirements of the public, which will benefit from this science. Given the international reach of this promising research and its clinical application, it is necessary for stem cell bank governance frameworks to be harmonized across jurisdictions.

  19. Blood-Forming Stem Cell Transplants

    MedlinePlus

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  20. 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 ...

  1. Can Stem Cell 'Patch' Help Heart Failure?

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_164475.html Can Stem Cell 'Patch' Help Heart Failure? Small improvement seen over ... Scientists report another step in the use of stem cells to help treat people with debilitating heart failure. ...

  2. 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.

  3. STEM Education is Missing This.......

    NASA Astrophysics Data System (ADS)

    Orr, Laura; Johnson, Milton; Miller, Alexandra; Rebull, Luisa M.

    2017-01-01

    STEM education gets a lot of attention in schools, media, politics, and funding. But while the acronym grows from STEM to STEAM to STREAM, we still see a lack of student participation in real science, using big data and building partnerships with professionals in the field, and real student growth in science achievement. After the NITARP experience, we believe that NITARP is a rich, demanding, and authentic experience for dedicated teachers and students that provides a caliber of learning that is hard, if not impossible, to achieve in the traditional classroom. This poster looks at what STEM still needs to be and become for it to be the driving force behind greater student involvement, interest, and increased academic performance in the sciences. We focus on our own experiences and that of our students; our different teaching backgrounds and school environments; and the effects we see on our students using traditional and new STEM education and participation in the NITARP program. We come from backgrounds and situations that range from urban to rural, middle to high school, wide socioeconomic variety, gender differences, as well as different exposures to STEM opportunities. We propose that traditional and current standards for STEM education are falling short of what is needed for students to truly experience, understand, and gain the skills to accurately apply and advance in science. Incoming and current science teachers at all levels are not provided with quality, realistic, or applicable preparation. NITARP is truly a STEM experience because it actually integrates the 4 fields and provides opportunities for students to experience the overlap of the 4 fields in an authentic way. The deep, long term exposure to authentic research and technology as well as opportunity to talk with working scientists in a variety of fields have a huge impact on the students and teachers alike. Exposure to programs and experiences like NITARP are needed to help drive and support STEM

  4. 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…

  5. 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…

  6. STEM Learning through Engineering Design: Impact on Middle Secondary Students' Interest towards STEM

    ERIC Educational Resources Information Center

    Shahali, Edy Hafizan Mohd; Halim, Lilia; Rasul, Mohamad Sattar; Osman, Kamisah; Zulkifeli, Mohd Afendi

    2017-01-01

    The purpose of this study was to identify students' changes of (i) interest toward STEM subjects and (ii) interest to pursuing STEM career after participating in non-formal integrated STEM education programme. The programme exposed students with integrated STEM education through project based learning involving the application of five phases…

  7. 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…

  8. Academic Success for STEM and Non-STEM Majors

    ERIC Educational Resources Information Center

    Whalen, Donald F; Shelley, Mack C., II

    2010-01-01

    Enrollment in STEM majors has improved recently, but there continues to be concern over students' retention in those majors, especially women and minority students. The purpose of this study is to develop an integrated understanding of how multiple predictor variables affect student degree attainment, and to ascertain how those variables' impact…

  9. A Peculiar Mutation Spectrum Emerging from Young Peruvian Patients with Hepatocellular Carcinoma

    PubMed Central

    Marchio, Agnès; Bertani, Stéphane; Rojas Rojas, Teresa; Doimi, Franco; Terris, Benoît; Deharo, Eric; Dejean, Anne; Ruiz, Eloy; Pineau, Pascal

    2014-01-01

    Hepatocellular carcinoma usually afflicts individuals in their later years following longstanding liver disease. In Peru, hepatocellular carcinoma exists in a unique clinical presentation, which affects patients around age 25 with a normal, healthy liver. In order to deepen our understanding of the molecular processes ongoing in Peruvian liver tumors, mutation spectrum analysis was carried out on hepatocellular carcinomas from 80 Peruvian patients. Sequencing analysis focused on nine genes typically altered during liver carcinogenesis, i.e. ARID2, AXIN1, BRAF, CTNNB1, NFE2L2, H/K/N-RAS, and TP53. We also assessed the transcription level of factors involved in the control of the alpha-fetoprotein expression and the Hippo signaling pathway that controls contact inhibition in metazoans. The mutation spectrum of Peruvian patients was unique with a major class of alterations represented by Insertions/Deletions. There were no changes at hepatocellular carcinoma-associated mutation hotspots in more than half of the specimens analyzed. Furthermore, our findings support the theory of a consistent collapse in the Hippo axis, as well as an expression of the stemness factor NANOG in high alpha-fetoprotein-expressing hepatocellular carcinomas. These results confirm the specificity of Peruvian hepatocellular carcinoma at the molecular genetic level. The present study emphasizes the necessity to widen cancer research to include historically neglected patients from South America, and more broadly the Global South, where cancer genetics and tumor presentation are divergent from canonical neoplasms. PMID:25502816

  10. [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.

  11. Breast Cancer Stem Cells in Antiestrogen Resistance

    DTIC Science & Technology

    2013-08-01

    stimulated by antiestrogens. The effects of antiestrogens on the ER-positive breast cancer stem/progenitor involve changes of both proliferation and...self-renewal capabilities of breast cancer stem/progenitor cells. The effects of antiestrogens on the ER- positive breast cancer stem/progenitor...potent tumor-seeding efficiency. . Fig 3. The effects of antiestrogens on the differentiation of ER-positive breast cancer stem cells expressing

  12. Adult stem cell therapy: dream or reality?

    PubMed

    Moraleda, Jose M; Blanquer, Miguel; Bleda, Patricia; Iniesta, Paqui; Ruiz, Francisco; Bonilla, Sonia; Cabanes, Carmen; Tabares, Lucía; Martinez, Salvador

    2006-12-01

    Adult stem cells may be an invaluable source of plastic cells for tissue regeneration. The bone marrow contains different subpopulations of adult stem cells easily accessible for transplantation. However the therapeutic value of adult stem cell is a question of debate in the scientific community. We have investigated the potential benefits of adult hematopoietic stem cell transplantation in animal models of demyelinating and motor neuron diseases. Our results suggest that transplantation of HSC have direct and indirect neuroregenerative and neuroprotective effects.

  13. 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…

  14. 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…

  15. 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…

  16. 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.

  17. 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…

  18. 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…

  19. 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…

  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. 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…

  2. 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…

  3. 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…

  4. [Therapeutic use of stem cells].

    PubMed

    Uzan, Georges

    2004-09-15

    Stem cells display important capacities of self renewing, proliferation and differentiation. Because those present in the embryo have the more remarkable properties, their potential use in the therapy of until now incurable degenerative diseases have been envisioned. Embryonic stem (ES) cells are located in the inner mass of the balstocyst at early stages of the development. Even in long-term cultures they still retain their undifferentiated features. Under specific culture conditions, ES cells can be committed into a variety of differentiation pathways, giving rise to large amounts of cells corresponding to different tissues (neurones, cardiomyocytes, skeletal muscle, etc.). However, producing these tissues from already established ES cell lines would lead to immune rejection when transplanted to patients. To prevent this pitfall and using the expertise accumulated by animal cloning by nucleus transfer, it has been proposed to adapt this technique to human ES cells. The therapeutic cloning consists in transferring the nucleus of somatic stem cells isolated from the patient into an enucleated oocyte, to allow blastocyst development from which ES cells will be derived. From these stem cells, compatible tissues will be then produced. The problem is that it is in theoretically possible to reimplant the cloned blastocyst into a surrogate mother for obtaining a baby genetically identical to the donor. This is called reproductive cloning. This worrying risk raises important ethic and legal questions.

  5. 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…

  6. 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

  7. 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…

  8. 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…

  9. Human fetal mesenchymal stem cells.

    PubMed

    O'Donoghue, Keelin; Chan, Jerry

    2006-09-01

    Stem cells have been isolated at all stages of development from the early developing embryo to the post-reproductive adult organism. However, the fetal environment is unique as it is the only time in ontogeny that there is migration of stem cells in large numbers into different organ compartments. While fetal neural and haemopoietic stem cells (HSC) have been well characterised, only recently have mesenchymal stem cells from the human fetus been isolated and evaluated. Our group have characterised in human fetal blood, liver and bone marrow a population of non-haemopoietic, non-endothelial cells with an immunophenotype similar to adult bone marrow-derived mesenchymal stem cells (MSC). These cells, human fetal mesenchymal stem cells (hfMSC), are true multipotent stem cells with greater self-renewal and differentiation capacity than their adult counterparts. They circulate in first trimester fetal blood and have been found to traffic into the maternal circulation, engrafting in bone marrow, where they remain microchimeric for decades after pregnancy. Though fetal microchimerism has been implicated in the pathogenesis of autoimmune disease, the biological role of hfMSC microchimerism is unknown. Potential downstream applications of hfMSC include their use as a target cell for non-invasive pre-natal diagnosis from maternal blood, and for fetal cellular and gene therapy. Using hfMSC in fetal therapy offers the theoretical advantages of avoidance of immune rejection, increased engraftment, and treatment before disease pathology sets in. Aside from allogeneic hfMSC in utero transplantation, the use of autologous hfMSC has been brought a step forward with the development of early blood sampling techniques, efficient viral transduction and clonal expansion. Work is ongoing to determine hfMSC fate post-transplantation in murine models of genetic disease. In this review we will examine what is known about hfMSC biology, as well as discussing areas for future research. The

  10. 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.

  11. Iatrogenic limbal stem cell deficiency.

    PubMed Central

    Holland, E J; Schwartz, G S

    1997-01-01

    PURPOSE: To describe a group of patients with limbal stem cell (SC) deficiency without prior diagnosis of a specific disease entity known to be causative of SC deficiency. METHODS: We performed a retrospective review of the records of all patients with ocular surface disease presenting to the University of Minnesota between 1987 and 1996. Patients were categorized according to etiology of limbal deficiency. Patients who did not have a specific diagnosis previously described as being causative for limbal deficiency were analyzed. Risk factors, clinical findings and sequelae were evaluated. RESULTS: Eight eyes of six patients with stem cell deficiency not secondary to a known diagnosis were described. All eyes had prior ocular surgery involving the corneoscleral limbus. Six eyes had been on chronic topical medications and all eyes had concurrent external disease such as pterygium, keratoconjunctivitis sicca, rosacea or herpes simplex virus keratitis. All eyes had superior quadrants affected corresponding to areas of prior limbal surgery. Sequelae of disease included corneal scarring and neo-vascularization, and five eyes had with visual acuity of 20/200 or worse. CONCLUSIONS: Because the epitheliopathy started peripherally and extended centrally in all patients, we feel it represents a stem cell deficiency. The fact that all patients were affected superiorly, at sites of a prior limbal surgical incision, points to surgical trauma to the SC as the likely major etiologic factor for the deficiency. The surgical trauma to the limbal SC probably made these cells more susceptible to damage from other external disease influences and toxicity from chronic topical medications. Because the stem cell deficiency is secondary to prior ocular surgery and chronic topical medications, we propose the term "iatrogenic limbal stem cell deficiency". Images FIGURE 1 FIGURE 2A FIGURE 2B FIGURE 3A FIGURE 3B PMID:9440165

  12. Embryonic stem cell patents and human dignity.

    PubMed

    Resnik, David B

    2007-09-01

    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.

  13. Stem Cells for Neurovascular Repair in Stroke

    PubMed Central

    Shinozuka, Kazutaka; Dailey, Travis; Tajiri, Naoki; Ishikawa, Hiroto; Kim, Dae Won; Pabon, Mibel; Acosta, Sandra; Kaneko, Yuji; Borlongan, Cesar V

    2013-01-01

    Stem cells exert therapeutic effects against ischemic stroke via transplantation of exogenous stem cells or stimulation of endogenous stem cells within the neurogenic niches of subventricular zone and subgranular zone, or recruited from the bone marrow through peripheral circulation. In this paper, we review the different sources of stem cells that have been tested in animal models of stroke. In addition, we discuss specific mechanisms of action, in particular neurovascular repair by endothelial progenitor cells, as key translational research for advancing the clinical applications of stem cells for ischemic stroke. PMID:24077523

  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. Emerging molecular approaches in stem cell biology.

    PubMed

    Jaishankar, Amritha; Vrana, Kent

    2009-04-01

    Stem cells are characterized by their ability to self-renew and differentiate into multiple adult cell types. Although substantial progress has been made over the last decade in understanding stem cell biology, recent technological advances in molecular and systems biology may hold the key to unraveling the mystery behind stem cell self-renewal and plasticity. The most notable of these advances is the ability to generate induced pluripotent cells from somatic cells. In this review, we discuss our current understanding of molecular similarities and differences among various stem cell types. Moreover, we survey the current state of systems biology and forecast future needs and direction in the stem cell field.

  16. 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

  17. Somatic stem cell biology and periodontal regeneration.

    PubMed

    Zhu, Bin; Liu, Yihan; Li, Dehua; Jin, Yan

    2013-01-01

    Somatic stem cells have been acknowledged for their ability to differentiate into multiple cell types and their capacity for self-renewal. Some mesenchymal stem cells play a dominant role in the repair and reconstruction of periodontal tissues. Both dental-derived and some non-dental-derived mesenchymal stem cells possess the capacity for periodontal regeneration under certain conditions with induced differentiation, proliferation, cellular secretion, and their interactions. Stem cell-based tissue engineering technology promises to bring improvements to periodontal regeneration, biologic tooth repair, and bioengineered implants. The present review discusses the roles and values of various somatic stem cells in periodontal regeneration.

  18. Cancer Stem Cells in Lung Tumorigenesis

    PubMed Central

    Kratz, Johannes R.; Yagui-Beltrán, Adam; Jablons, David M.

    2011-01-01

    Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continued research in the field of lung cancer stem cell biology is vital, as ongoing efforts promise to yield new prognostic and therapeutic targets. PMID:20493987

  19. Notch signaling in cancer stem cells.

    PubMed

    Wang, Jialiang; Sullenger, Bruce A; Rich, Jeremy N

    2012-01-01

    Subpopulations of cancer cells with stem cell-like characteristics, termed cancer stem cells, have been identified in a wide range of human cancers. Cancer stem cells are defined by their ability to self-renew as well as recapitulate the original heterogeneity of cancer cells in culture and in serial xenotransplants. Not only are cancer stem cells highly tumorigenic, but these cells are implicated in tumor resistance to conventional chemotherapy and radiotherapy, thus highlighting their significance as therapeutic targets. Considerable similarities have been found between cancer stem cells and normal stem cells on their dependence on certain signaling pathways. More specifically, the core stem cell signaling pathways, such as the Wnt, Notch and Hedgehog pathways, also critically regulate the self-renewal and survival of cancer stem cells. While the oncogenic functions of Notch pathway have been well documented, its role in cancer stem cells is just emerging. In this chapter, we will discuss recent advances in cancer stem cell research and highlight the therapeutic potential of targeting Notch in cancer stem cells.

  20. 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.