Search

Your search keyword '"Spitsbergen, Jan M."' showing total 132 results
Start Over Author "Spitsbergen, Jan M."
132 results on '"Spitsbergen, Jan M."'

2. The Zebrafish Model for Liver Carcinogenesis

Author

Gong, Zhiyuan, Koh, Chor Hui Vivien, Nguyen, Anh Tuan, Zhan, Huiqing, Li, Zhen, Lam, Siew Hong, Spitsbergen, Jan M., Emelyanov, Alexander, Parinov, Serguei, Wang, Xin Wei, editor, Grisham, Joe W., editor, and Thorgeirsson, Snorri S., editor

Published
2011
Full Text
View/download PDF

4. Nonlesions, Misdiagnoses, Missed Diagnoses, and Other Interpretive Challenges in Fish Histopathology Studies: A Guide for Investigators, Authors, Reviewers, and Readers

Author

Wolf, Jeffrey C., Baumgartner, Wes A., Blazer, Vicki S., Camus, Alvin C., Engelhardt, Jeffery A., Fournie, John W., Frasca, Salvatore, Jr., Groman, David B., Kent, Michael L., Khoo, Lester H., Law, Jerry M., Lombardini, Eric D., Ruehl-Fehlert, Christine, Segner, Helmut E., Smith, Stephen A., Spitsbergen, Jan M., Weber, Klaus, and Wolfe, Marilyn J.

Published
2015
Full Text
View/download PDF

6. The Zebrafish Model for Liver Carcinogenesis

Author

Gong, Zhiyuan, primary, Koh, Chor Hui Vivien, additional, Nguyen, Anh Tuan, additional, Zhan, Huiqing, additional, Li, Zhen, additional, Lam, Siew Hong, additional, Spitsbergen, Jan M., additional, Emelyanov, Alexander, additional, and Parinov, Serguei, additional

Published
2010
Full Text
View/download PDF

13. Stress Leukogram Induced by Acute and Chronic Stress in Zebrafish (Danio rerio)

Author

Grzelak, Agata K, Davis, Daniel J, Caraker, Susan M, Crim, Marcus J, Spitsbergen, Jan M, and Wiedmeyer, Charles E

Subjects
Leukocyte Count, Hydrocortisone, Stress, Physiological, Lymphopenia, Fish Model, Animals, Zebrafish
Abstract

The use of zebrafish (Danio rerio) as an animal model for experimental studies of stress has increased rapidly over the years. Although many physiologic and behavioral characteristics associated with stress have been defined in zebrafish, the effects of stress on hematologic parameters have not been described. The purpose of our study was to induce a rise in endogenous cortisol through various acute and chronic stressors and compare the effects of these stressors on peripheral WBC populations. Acutely stressed fish underwent dorsal or full-body exposure to air for 3 min, repeated every 30 min over the course of 90 min. Chronically stressed fish underwent exposure to stressors twice daily over a period of 5 d. After the last stressful event, fish were euthanized, and whole blood and plasma were obtained. A drop of whole blood was used to create a blood smear, which was subsequently stained with a modified Wright-Giemsa stain and a 50-WBC differential count determined. Plasma cortisol levels were determined by using a commercially available ELISA. Endogenous cortisol concentrations were significantly higher in both stressed groups as compared with control fish. Acutely stressed fish demonstrated significant lymphopenia, monocytosis, and neutrophilia, compared with unstressed, control fish. Chronic stress induced lymphopenia and monocytosis but no significant changes in relative neutrophil populations in zebrafish. The changes in both stressed groups most likely are due to increases in endogenous cortisol concentrations and represent the first description of a stress leukogram in zebrafish.

Published
2017

20. Nonlinear Cancer Response at Ultralow Dose: A 40800-Animal ED 001 Tumor and Biomarker Study

Author

Bailey, George S., Swenberg, James A., Spitsbergen, Jan M., Williams, David E., Pereira, Clifford B., Reddy, Ashok P., Orner, Gayle A., Harttig, Ulrich, Baird, William, and Hendricks, Jerry D.

Abstract

Assessment of human cancer risk from animal carcinogen studies is severely limited by inadequate experimental data at environmentally relevant exposures, and procedures requiring modeled extrapolations many orders of magnitude below observable data. We used rainbow trout, an animal model well suited to ultra low-dose carcinogenesis research, to explore dose-response down to a targeted 10 excess liver tumors per 10,000 animals (ED001). A total of 40,800 trout were fed 0–225 ppm dibenzo[a,l]pyrene (DBP) for four weeks, sampled for biomarker analyses, and returned to control diet for nine months prior to gross and histologic examination. Suspect tumors were confirmed by pathology, and resulting incidences were modeled and compared to the default EPA LED10 linear extrapolation method. The study provided observed incidence data down to two above-background liver tumors per 10,000 animals at lowest dose (that is, an un-modeled ED0002 measurement). Among nine statistical models explored, three were determined to fit the liver data well - linear probit, quadratic logit, and Ryzin-Rai. None of these fitted models is compatible with the LED10 default assumption, and all fell increasingly below the default extrapolation with decreasing DBP dose. Low-dose tumor response was also not predictable from hepatic DBP-DNA adduct biomarkers, which accumulated as a power function of dose (adducts = 100 * DBP1.31). Two-order extrapolations below the modeled tumor data predicted DBP doses producing one excess cancer per million individuals (ED10−6) that were 500–1500-fold higher than that predicted by the five-order LED10 extrapolation. These results are considered specific to the animal model, carcinogen, and protocol used. They provide the first experimental estimation in any model of the degree of conservatism that may exist for the EPA default linear assumption for a genotoxic carcinogen.

Published
2009
Full Text
View/download PDF

21. Nonlesions, Misdiagnoses, Missed Diagnoses, and Other Interpretive Challenges in Fish Histopathology Studies

Author

Wolf, Jeffrey C., primary, Baumgartner, Wes A., additional, Blazer, Vicki S., additional, Camus, Alvin C., additional, Engelhardt, Jeffery A., additional, Fournie, John W., additional, Frasca, Salvatore, additional, Groman, David B., additional, Kent, Michael L., additional, Khoo, Lester H., additional, Law, Jerry M., additional, Lombardini, Eric D., additional, Ruehl-Fehlert, Christine, additional, Segner, Helmut E., additional, Smith, Stephen A., additional, Spitsbergen, Jan M., additional, Weber, Klaus, additional, and Wolfe, Marilyn J., additional

Published
2014
Full Text
View/download PDF

31. Finfish and aquatic invertebrate pathology resources for now and the future

Author

Spitsbergen, Jan M., primary, Blazer, Vicki S., additional, Bowser, Paul R., additional, Cheng, Keith C., additional, Cooper, Keith R., additional, Cooper, Timothy K., additional, Frasca, Salvatore, additional, Groman, David B., additional, Harper, Claudia M., additional, Law, Jerry M. (Mac), additional, Marty, Gary D., additional, Smolowitz, Roxanna M., additional, St. Leger, Judy, additional, Wolf, Douglas C., additional, and Wolf, Jeffrey C., additional

Published
2009
Full Text
View/download PDF

32. Oncogenic KRAS promotes malignant brain tumors in zebrafish.

Author

Bensheng Ju, Wenbiao Chen, Orr, Brent A., Spitsbergen, Jan M., Sujuan Jia, Eden, Christopher J., Henson, Hannah E., and Taylor, Michael R.

Subjects
RHABDOMYOSARCOMA, LIVER cancer, ONCOGENIC proteins, CENTRAL nervous system, BRAIN tumors, GLIAL fibrillary acidic protein, IMMUNOSTAINING
Abstract

Background: Zebrafish have been used as a vertebrate model to study human cancers such as melanoma, rhabdomyosarcoma, liver cancer, and leukemia as well as for high-throughput screening of small molecules of therapeutic value. However, they are just emerging as a model for human brain tumors, which are among the most devastating and difficult to treat. In this study, we evaluated zebrafish as a brain tumor model by overexpressing a human version of oncogenic KRAS (KRASG12V). Methods: Using zebrafish cytokeratin 5 (krt5) and glial fibrillary acidic protein (gfap) gene promoters, we activated Ras signaling in the zebrafish central nervous system (CNS) through transient and stable transgenic overexpression. Immunohistochemical analyses were performed to identify activated pathways in the resulting brain tumors. The effects of the MEK inhibitor U0126 on oncogenic KRAS were evaluated. Results: We demonstrated that transient transgenic expression of KRASG12V in putative neural stem and/or progenitor cells induced brain tumorigenesis. When expressed under the control of the krt5 gene promoter, KRASG12V induced brain tumors in ventricular zones (VZ) at low frequency. The majority of other tumors were composed mostly of spindle and epithelioid cells, reminiscent of malignant peripheral nerve sheath tumors (MPNSTs). In contrast, when expressed under the control of the gfap gene promoter, KRASG12V induced brain tumors in both VZs and brain parenchyma at higher frequency. Immunohistochemical analyses indicated prominent activation of the canonical RAS-RAF-ERK pathway, variable activation of the mTOR pathway, but no activation of the PI3K-AKT pathway. In a krt5-derived stable and inducible transgenic line, expression of oncogenic KRAS resulted in skin hyperplasia, and the MEK inhibitor U0126 effectively suppressed this pro-proliferative effects. In a gfap-derived stable and inducible line, expression of oncogenic KRAS led to significantly increased mitotic index in the spinal cord. Conclusions: Our studies demonstrate that zebrafish could be explored to study cellular origins and molecular mechanisms of brain tumorigenesis and could also be used as a platform for studying human oncogene function and for discovering oncogenic RAS inhibitors. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

33. Cardiovascular Toxicity of Environmental Contaminants to Developing Fish -- Molecular Mechanisms.

Author

CORNELL UNIV ITHACA NY, Spitsbergen, Jan M., CORNELL UNIV ITHACA NY, and Spitsbergen, Jan M.

Abstract

Both developing zebrafish and medaka are exquisitely sensitive to the cardiovascular toxicity of all-trans retinoic acid (RA) between fertilization and the onset of blood circulation, with incubation medium concentrations of 3-5 ng/ml applied during the blastula stage causing pericardial edema with subsequent circulatory stasis and severe subcutaneous edema and ascites. The sensitivity of both species to RA decreased dramatically during development, with over 40 ng/ml required to cause edema with embryos treated after body pigmentation, and over 300 ng/ml required to cause edema in hatched fry. Zebrafish and medaka embryos are comparably sensitive to the cardiovascular toxicity of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin when treated at fertilization, with 2-3 ng/g TCDD in embryos causing lethality. Thus these species are approximately 40X less sensitive to the cardiovascular toxicity and lethality caused by TCDD exposure early in development than are lake trout embryos in which the LCSO is 0.065 ng/g. Both fish species demonstrate a TCDD cardiovascular toxicity syndrome similar to that seen following RA exposure, with initial pericardial edema followed by circulatory stasis, subcutaneous edema and ascites. Histologic lesions in TCDD-treated zebrafish included ballooning degeneration and necrosis of brain and epithelial tissues such as kidney, pancreas and liver. Molecular components of basement membrane of cardiovascular and epithelial tissues, including fibronectin, collagen IV and laminin, have been revealed in frozen sections of zebrafish and medaka using immunoperoxidase or immunofluorescence detection methods.

Published
1995

41. Luna stain, an improved selective stain for detection of microsporidian spores in histologic sections.

Author

Peterson, Tracy S., Spitsbergen, Jan M., Feist, Stephen W., and Kent, Michael L.

Subjects
GRAM'S stain, BACTERIAL spores, MICROSPORIDIA, EOSINOPHILS, CHITIN, AQUATIC animals, DISEASES
Abstract

The article discusses a study which compared the Luna stain to the Gram, Fite's acid fast, Giemsa and H&E stains on 8 stains including Loma salmonae, Glugea anomala, and Pseudoloma neurophilia. It was discovered that the Luna stain, used to highlight eosinophils, red blood cells, and chitin in arthropods and other invertebrates, also stains spores of Pseudoloma neurophilia. The study found that the Luna stain performed better for detection of 6 of the 8 microsporidia and Gram stain was superior for the 2 microsporidia from invertebrates.

Published
2011
Full Text
View/download PDF

44. A transgenic zebrafish liver tumor model with inducible Myc expression reveals conserved Myc signatures with mammalian liver tumors

Author

Li, Zhen, Zheng, Weiling, Wang, Zhengyuan, Zeng, Zhiqiang, Zhan, Huiqing, Li, Caixia, Zhou, Li, Yan, Chuan, Spitsbergen, Jan M., and Gong, Zhiyuan

Abstract

Myc is a pleiotropic transcription factor that is involved in many cellular activities relevant to carcinogenesis, including hepatocarcinogenesis. The zebrafish has been increasingly used to model human diseases and it is particularly valuable in helping to identify common and conserved molecular mechanisms in vertebrates. Here we generated a liver tumor model in transgenic zebrafish by liver-specific expression of mouse Myc using a Tet-On system. Dosage-dependent induction of Myc expression specifically in the liver was observed in our Myc transgenic zebrafish, TO(Myc), and the elevated Myc expression caused liver hyperplasia, which progressed to hepatocellular adenoma and carcinoma with prolonged induction. Next generation sequencing-based transcriptomic analyses indicated that ribosome proteins were overwhelmingly upregulated in the Myc-induced liver tumors. Cross-species analyses showed that the zebrafish Myc model correlated well with Myc transgenic mouse models for liver cancers. The Myc-induced zebrafish liver tumors also possessed molecular signatures highly similar to human those of hepatocellular carcinoma. Finally, we found that a small Myc target gene set of 16 genes could be used to identify liver tumors due to Myc upregulation. Thus, our zebrafish model demonstrated the conserved role of Myc in promoting hepatocarcinogenesis in all vertebrate species.

Published
2013
Full Text
View/download PDF

45. 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters cardiovascular and craniofacial development and function in sac fry of rainbow trout (Oncorhynchus mykiss).

Author

Hornung, Michael W., Spitsbergen, Jan M., and Peterson, Richard E.

Subjects
CARDIOVASCULAR diseases, TETRACHLORODIBENZODIOXIN, RAINBOW trout, YOLK sac, EDEMA, VELOCARDIOFACIAL syndrome, DWARFISM
Abstract

Hallmark signs of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in rainbow trout sac fry, are yolk sac edema, hemorrhage, craniofacial malformation, and growth retardation culminating in mortality. Our objective was to determine the role of cardiovascular dysfunction in the development of this toxicity. An embryo-toxic TCDD dose (385 pg/g egg) caused a progressive reduction in blood flow in rainbow trout sac fry manifested first and most dramatically in the 1st and 2nd branchial arches and vessels perfusing the lower jaw. Blood flow was reduced later in the infraorbital artery and occipital vein of the head as well as segmental vessels and caudal vein of the trunk. Reduced perfusion occurred last in gill branchial arteries involved with oxygen uptake and the subintestinal vein and vitelline vein involved with nutrient uptake. Although heart rate throughout sac fry development was not affected, heart size at 50 days post-fertilization (dpf) was reduced far more than body weight or length, suggesting that the progressive circulatory failure caused by TCDD is associated with reduced cardiac output. Craniofacial development was arrested near hatch, giving rise to craniofacial malformations in which the jaws and anterior nasal structures were underdeveloped. Unlike the medaka embryo, in which TCDD cases apoptosis in the medial yolk vein, endothelial cell death was not observed in rainbow trout sac fry. These findings suggest a primary role for arrested heart development and reduced perfusion of tissues with blood in the early-life stage toxicity of TCDD in trout. [ABSTRACT FROM PUBLISHER]

Published
1999
Full Text
View/download PDF

46. An inducible krasV12 transgenic zebrafish model for liver tumorigenesis and chemical drug screening

Author

Nguyen, Anh Tuan, Emelyanov, Alexander, Koh, Chor Hui Vivien, Spitsbergen, Jan M., Parinov, Serguei, and Gong, Zhiyuan

Abstract

Because Ras signaling is frequently activated by major hepatocellular carcinoma etiological factors, a transgenic zebrafish constitutively expressing the krasV12 oncogene in the liver was previously generated by our laboratory. Although this model depicted and uncovered the conservation between zebrafish and human liver tumorigenesis, the low tumor incidence and early mortality limit its use for further studies of tumor progression and inhibition. Here, we employed a mifepristone-inducible transgenic system to achieve inducible krasV12 expression in the liver. The system consisted of two transgenic lines: the liver-driver line had a liver-specific fabp10 promoter to produce the LexPR chimeric transactivator, and the Ras-effector line contained a LexA-binding site to control EGFP-krasV12 expression. In double-transgenic zebrafish (driver-effector) embryos and adults, we demonstrated mifepristone-inducible EGFP-krasV12 expression in the liver. Robust and homogeneous liver tumors developed in 100% of double-transgenic fish after 1 month of induction and the tumors progressed from hyperplasia by 1 week post-treatment (wpt) to carcinoma by 4 wpt. Strikingly, liver tumorigenesis was found to be ‘addicted’ to Ras signaling for tumor maintenance, because mifepristone withdrawal led to tumor regression via cell death in transgenic fish. We further demonstrated the potential use of the transparent EGFP-krasV12 larvae in inhibitor treatments to suppress Ras-driven liver tumorigenesis by targeting its downstream effectors, including the Raf-MEK-ERK and PI3K-AKT-mTOR pathways. Collectively, this mifepristone-inducible and reversible krasV12 transgenic system offers a novel model for understanding hepatocarcinogenesis and a high-throughput screening platform for anti-cancer drugs.

Published
2012
Full Text
View/download PDF

47. Fumonisin B1Promotes Aflatoxin B1and N-Methyl-N′-nitro-nitrosoguanidine-Initiated Liver Tumors in Rainbow Trout

Author

Carlson, David B, Williams, David E, Spitsbergen, Jan M, Ross, P.Frank, Bacon, Charles W, Meredith, Filmore I, and Riley, Ronald T

Abstract

Laboratory studies have described the carcinogenicity of fumonisin B1(FB1) in rodents and epidemiological evidence suggests an association between FB1(a mycotoxin produced by Fusarium moniliforme) and cancer in humans. This study was designed to reveal in rainbow trout, a species with very low spontaneous tumor incidence, if FB1was (i) a complete carcinogen, in the absence of an initiator; (ii) a promoter of liver tumors in fish initiated as fry with aflatoxin B1(AFB1); and (iii) a promoter of liver, kidney, stomach, or swim bladder tumors in fish initiated as fry with N-methyl-N′-nitro-nitrosoguanidine (MNNG). FB1was not a complete carcinogen in trout. No tumors were observed in any tissue of fish fed diets containing 0, 3.2, 23, or 104 ppm FB1for a total of 34 weeks (4 weeks FB1exposure, 2 weeks outgrowth on control diet, followed by 30 weeks FB1diet) in the absence of a known initiator. FB1promoted AFB1initiated liver tumors in fish fed ≥23 ppm FB1for 42 weeks. A 1-week pretreatment of FB1did not alter the amount of liver [3H]AFB1DNA adducts, which suggests that short-term exposure to FB1will not alter phase I or phase II metabolism of AFB1. In MNNG-initiated fish, liver tumors were promoted in the 104 ppm FB1treatment (42 weeks), but FB1did not promote tumors in any other tissue. Tumor incidence decreased in kidney and stomach in the 104 ppm FB1treatment of MNNG-initiated trout. The FB1promotional activity in AFB1-initiated fish was correlated with disruption of sphingolipid metabolism, suggesting that alterations in associated sphingolipid signaling pathways are potentially responsible for the promotional activity of FB1in AFB1-initiated fish.

Published
2001
Full Text
View/download PDF

50. Males develop faster and more severe hepatocellular carcinoma than females in krasV12 transgenic zebrafish.

Author

Li, Yan, Li, Hankun, Spitsbergen, Jan M., and Gong, Zhiyuan

Abstract

Hepatocellular carcinoma (HCC) is more prevalent in men than women, but the reason for this gender disparity is not well understood. To investigate whether zebrafish could be used to study the gender disparity of HCC, we compared the difference of liver tumorigenesis between female and male fish during early tumorigenesis and long-term tumor progression in our previously established inducible and reversible HCC model - the krasV12 transgenic zebrafish. We found that male fish developed HCC faster than females. The male tumors were more severe from the initiation stage, characteristic of higher proliferation, activation of WNT/β-catenin pathway and loss of cell adhesion. During long-term tumor progression, the male tumors developed into more advanced multi-nodular tumors, whereas the female tumors remain uniform and homogenous. Moreover, regression of male tumors required longer time. We further investigated the role of sex hormones in krasV12 transgenic fish. Estrogen treatment showed tumor suppressing effect during early tumorigenesis through inhibiting cell proliferation, whereas androgen accelerated tumor growth by promoting cell proliferation. Overall, our study presented the zebrafish as a useful animal model for study of gender disparity of HCC. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results