N-ethyl-N-nitrosourea induced brain tumors in rats monitored by nuclear magnetic resonance imaging, plasma proton nuclear magnetic resonance spectroscopy and microscopy

Lasker, Sigmund E.; Iatropoulos, Michael J.; Hecht, Stephen S.; Misra, Bijaya; Amin, Shantu; Zang, Edith; Williams, Gary M.

doi:10.1016/0304-3835(92)90135-i

Cited by 4 publications

(4 citation statements)

References 20 publications

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“…Unfortunately, other individuals with altered serum lipid profiles (such as pregnant women [Fossel et al, 1986] or patients with ''premalignant'' disease [Okunieff et al, 1990]) displayed similar decreases in resonance linewidths, leading many to question the specificity of the NMR blood test for cancer. Since that time, various groups have continued to study the analysis of linewidth data from sera for its applicability as a screening tool for cancer, with results remaining mixed and inconclusive (Chmurny et al, 1988;Schalk et al, 1989;Verdery et al, 1989;Gadenholt et al, 1990;Carlier et al, 1991;Lasker et al, 1992;Leray and de Certaines, 1994). The application of NMR metabonomics to the analysis of serum for markers indicative of cancer is one potential new method being explored for early cancer detection.…”

Section: Discussionmentioning

confidence: 96%

1H-NMR metabonomics analysis of sera differentiates between mammary tumor-bearing mice and healthy controls

Whitehead¹,

Monzavi‐Karbassi

Kieber‐Emmons

2005

Metabolomics

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Global analysis of 1 H-NMR spectra of serum is an appealing approach for the rapid detection of cancer. To evaluate the usefulness of this method in distinguishing between mammary tumor-bearing mice and healthy controls, we conducted 1 H-NMR metabonomic analyses on serum samples obtained from the following: 10 mice inoculated with a highly-metastatic mammary carcinoma cell line, 10 mice inoculated with a ''normally'' metastatic mammary carcinoma cell line, and 10 healthy controls. Following standard spectral processing and subsequent data reduction, we applied unsupervised Principal Component Analysis (PCA) to determine if unique metabolic fingerprints for different categories of metastatic breast cancer in serum exist. The PCA method correctly separated sera of tumor-bearing mice from that of normal healthy controls, as shown using the scores plot which indicated that sera classes from tumor-bearing mice did not share multivariate space with that from healthy controls. In addition, this technique was capable of distinguishing between classes of varying metastatic ability in this system. Metabolites apparently responsible for separation between diseased and healthy mice include lactate, taurine, choline, and sugar moieties. Results of this study suggest that 1 H-NMR spectra of mouse serum analyzed using PCA statistical methods indicate separation of tumor-bearing mice from healthy normal controls, justifying further study of the use of 1 H-NMR metabonomics for cancer detection using serum.

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Section: Discussionmentioning

confidence: 96%

1H-NMR metabonomics analysis of sera differentiates between mammary tumor-bearing mice and healthy controls

Whitehead¹,

Monzavi‐Karbassi

Kieber‐Emmons

2005

Metabolomics

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“…As non-invasive imaging of brain tumors is becoming more common, MRI was used in order to obtain a more accurate determination of the number, incidence, and growth rate of the tumors. Initially applied to transplanted tumor animal models to measure growth, several groups have also used it to detect tumors produced by ENU exposure MRI [33][34][35][36].…”

Section: Discussionmentioning

confidence: 99%

“…Non-invasive MR imaging has demonstrated the capability to perform repeated measurement of tumors derived from orthotopically implanted cell lines and to measure changes in growth rates caused by therapy [32]. Additionally, ENU-induced tumors have been reported as imagable by magnetic resonanace imaging (MRI) [33][34][35][36]. To date, no study has reported the effect of any therapy on chemically induced brain tumors true incidence or growth rates.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Kish

Blaivas

Strawderman

et al. 2001

Journal of Neuro-Oncology

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Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their preventive or therapeutic efficacy in these tumors, requires the use of animal models. Spontaneous gliomas develop in models of chemically induced carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU) rat model. However, without the ability to detect initial tumor formation, multiplicity or to measure growth rates, it is difficult to test compounds for their interventional or preventional capabilities. In this study Fisher-334 rats, treated transplacentally with ENU, underwent magnetic resonance imaging (MRI) examination in order to evaluate this approach for detection of tumor formation and growth. ENU-induced intracranial cerebral tumors were first observable in T2-weighted images beginning at 4 months of age and grew with a mean doubling time of 0.487 +/- 0.112 months. These tumors were found histologically to be predominately mixed gliomas. Two therapeutic interventions were evaluated using MRI, vitamin A (all-trans retinol palmitate, RP), as a chemopreventative agent and the anti-angiogenic drug SU-5416. RP was found to significantly delay the time to first tumor observation by one month (P = 0.05). No differences in rates of tumor formation or growth rates were observed between control and RP-treated groups. MRI studies of rats treated with SU-5416 resulted in reduction in tumor growth rates compared to matched controls. These results show that MRI can be used to provide novel information relating to the therapeutic efficacy of agents against the ENU-induced tumor model.

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“…This notion is strengthened both by the fact that mAb RB13-6 detects precursor cells for a subtype of astrocytes, ependymal cells and microglia (Blass-Kampmann S, Kindler-Rohrborn A, Rajewsky MF, in preparation) and by the histological appearance of rat brain tumors induced by a transplacental pulse of EtNU in vivo. The majority of brain tumors induced transplacentally during prenatal development display a mixed phenotype with immature astroglial and oligodendroglial components, whereas tumors with ependymal phenotypes occur relatively rarely [15, 20,301. If brain tumors are induced in the neonatal rat or postnatally, a remarkable shift to the occurrance of oligodendrogliomas is found and only a small number of mixed gliomas can be diagnosed [13, 241. Due to the fact that the histology of the frozen sections stained with the four mAbs was not very well preserved, it was not possible to conclude from these experiments which tumor cell type(s) (astroglial versus oligodendroglial) expressed the mAb RB 13-6 binding antigen.…”

Section: Discussionmentioning

confidence: 99%

Surface antigens of cell subpopulations in prenatal rat brain are expressed in a characteristic non-random pattern on their ethylnitrosourea-induced malignant counterparts

Kindler‐Röhrborn¹,

Blass-Kampmann²,

Lennartz³

et al. 1994

Differentiation

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Selective induction of neural tumors in the rat by single-dose exposure of the immature nervous system to ethylnitrosourea (EtNU) is a model for the study of cell lineage-, differentiation stage-, and carcinogen-dependent mechanisms in neuro-oncogenesis. Overall yields and relative frequencies of different types of neural tumors vary with the developmental window chosen for the EtNU-pulse. Precursor cells belonging to different neural lineages and targeted by the carcinogen at distinct developmental stages may thus bear a differential risk of malignant conversion. To specify subpopulations of neural precursors in fetal (prenatal day 18) BDIX-rat brain, four monoclonal antibodies (mAbs) recognizing cell surface differentiation antigens were used: mAb RB 13-2 directed against 0-acetylated gangliosides and binding to approximately 36% of fetal brain cells (FBC); mAb RB 13-6 recognizing a 130 kDa glycoprotein (expressed by approximately 8% of FBC); and mAbs RB21-7 and RB21-15 which bind, respectively, to embryonal neural cell adhesion molecules (N-CAM) and a 24 kDa protein (expressed by approximately 55% and 12% of FBC). Antigen expression profiles were compared with those of 14 primary brain tumors and 16 malignant neural cell lines, all of which had been induced by EtNU on prenatal day 18 in vivo. Monoclonal antibodies RB13-2 and RB21-7 did not bind to any of the tumors or cell lines. In contrast, mAbs RB13-6 and RB21-15 both reacted with 14/14 tumors, and with 16/16 and 10116 cell lines, respectively. Expression of the latter antigens might thus specify lineage-specific stages of FBC development/differentiation particularly susceptible to EtNU-induced malignant transformation. Two-color fluorescence analyses revealed three subsets of FBC binding mAb RB13-6 (RB13-2+/ RB13-6+/ RB2 1-1 5-; RB 13-2-mB 13-6+mB2 1-1%; and RB 13-2-/

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N-ethyl-N-nitrosourea induced brain tumors in rats monitored by nuclear magnetic resonance imaging, plasma proton nuclear magnetic resonance spectroscopy and microscopy

Cited by 4 publications

References 20 publications

1H-NMR metabonomics analysis of sera differentiates between mammary tumor-bearing mice and healthy controls

1H-NMR metabonomics analysis of sera differentiates between mammary tumor-bearing mice and healthy controls

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Surface antigens of cell subpopulations in prenatal rat brain are expressed in a characteristic non-random pattern on their ethylnitrosourea-induced malignant counterparts

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