N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

Ranes, M K; El-Abbadi, Mohga; Manfredi, Mark; Mukherjee, Purna; Platt, Frances M.; Seyfried, Thomas N.

doi:10.1054/bjoc.2000.1713

Cited by 44 publications

(50 citation statements)

References 41 publications

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“…In this study, we evaluated the effects of DR on the orthotopic growth of two mouse syngeneic brain tumors, CT-2A (malignant astrocytoma) and ependymoblastoma (EPEN), and the human U87-MG glioma xenograft. These mouse and human tumors differ in cell origin, angiogenicity, host environment, and biochemical composition, as described previously (27)(28)(29)(30)(31). Whereas tumor growth was rapid with unrestricted feeding, a moderate 40% DR significantly enhanced apoptosis while reducing growth and vascularity in all brain tumor models.…”

Section: Introductionmentioning

confidence: 59%

“…The EPEN tumor arose in the cerebral ventricle and was characterized as an EPEN, whereas the CT-2A tumor arose in the cerebral cortex and was characterized as an anaplastic astrocytoma (28,34). The morphological, biochemical, and growth characteristics of these mouse brain tumors have been described previously (27)(28)(29)(35)(36)(37). The human cell line U87-MG was originally derived from a malignant glioma (glioblastoma) and grown as a nonsyngeneic xenograft in the SCID mice (31).…”

Section: Introductionmentioning

confidence: 85%

“…The mouse and human tumors were implanted into the cerebral cortex of the B6 or SCID mice, respectively, using a trocar as we described previously (29,36). Briefly, mice were anesthetized with 2,2,2-tribromoethanol (Sigma Aldrich) intraperitoneally, and their heads were shaved and swabbed with 70% ethanol under sterile conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Briefly, mice were anesthetized with 2,2,2-tribromoethanol (Sigma Aldrich) intraperitoneally, and their heads were shaved and swabbed with 70% ethanol under sterile conditions. Small tumor pieces (about 1 mm 3 ) from a donor mouse were implanted into the right cerebral hemisphere of anesthetized recipient mice as we described recently (29). All of the mice that recovered from the surgical procedure were returned to their cages when fully active.…”

Section: Introductionmentioning

confidence: 99%

“…Greater than 98% of the implanted mice recover from the procedure. Initiation of tumors from intact tumor pieces is preferable to initiation from cultured cells because the pieces already contain an established microenvironment that facilitates tumor growth (29).…”

Section: Introductionmentioning

confidence: 99%

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Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors

Mukherjee

Abate

Seyfried

2004

Clinical Cancer Research

157

154

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Purpose: The antiangiogenic and proapoptotic mechanisms of dietary caloric restriction (DR) are unknown. In this study, we evaluated the effects of moderate (40%) DR on the orthotopic growth of mouse and human brain tumors that differ in cell origin, angiogenicity, host environment, and biochemical composition.Experimental Design: A malignant mouse astrocytoma (CT-2A) and a human glioma (U87-MG) were highly angiogenic and fast growing, whereas a mouse ependymoblastoma was less vascularized and slower growing. The tumors were evaluated for growth, cell proliferation, microvessel density, and apoptosis under DR and ad libitum feeding. Serum vascular endothelial growth factor and insulin-like growth factor I levels were examined as angiogenic biomarkers.Results: DR significantly decreased vascularity (factor VIII) and increased apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling) in all tumors. These effects were associated with enhanced caspase-3 and poly-(ADP-ribose) polymerase cleavage in the CT-2A and ependymoblastoma tumors, but not in the U87-MG tumor. DR also caused reductions of serum insulin-like growth factor I and glucose levels.Conclusions: DR had significant antiangiogenic and proapoptotic effects in the three distinct brain tumor models. DR, however, had differential effects on cell proliferation, biomarkers of angiogenesis, and apoptosis, suggesting multiple mechanisms of action. Because extensive angiogenesis and resistance to apoptosis are hallmarks of gliomas, this study provides new insight into the molecular basis of the DR-induced inhibition of brain tumor growth.

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Section: Introductionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors

Mukherjee

Abate

Seyfried

2004

Clinical Cancer Research

157

154

View full text Add to dashboard Cite

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Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Huysentruyt

Mukherjee

Banerjee

et al. 2008

Intl Journal of Cancer

154

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Metastasis is the process by which cancer cells disseminate from the primary neoplasm and invade surrounding tissue and distant organs, and is the primary cause of morbidity and mortality for cancer patients. Most conventional cancer therapies are ineffective in managing tumor metastasis. This has been due in large part to the absence of in vivo metastatic models that represent the full spectrum of metastatic disease. Here we identify 3 new spontaneously arising tumors in the inbred VM mouse strain, which has a relatively high incidence of CNS tumors. Two of the tumors (VM-M2 and VM-M3) reliably expressed all of the major biological processes of metastasis to include local invasion, intravasation, immune system survival, extravasation and secondary tumor formation involving liver, kidney, spleen, lung and brain. Metastasis was assessed through visual organ inspection, histology, immunohistochemistry and bioluminescence imaging. The metastatic VM tumor cells also expressed multiple properties of macrophages including morphological appearance, surface adhesion, phagocytosis, total lipid composition (glycosphingolipids and phospholipids) and gene expression (CD11b, Iba1, F4/80, CD68, CD45 and CXCR4). The third tumor (VM-NM1) grew rapidly and expressed properties of neural stem/progenitor cells, but was neither invasive nor metastatic. Our data indicate that spontaneous brain tumors can arise from different cell types in VM mice and that metastatic cancer can represent a disease of macrophage-like cells similar to those described in several human metastatic cancers.The new VM tumor model will be useful for defining the biological processes of cancer metastasis and for evaluating potential therapies for tumor management. ' 2008 Wiley-Liss, Inc.Key words: metastasis; microglia; gangliosides; neural stem cell; glioblastoma Metastasis is the process by which cancer cells disseminate from the primary neoplasm and invade surrounding tissue and distant organs and is the primary cause of morbidity and mortality for cancer patients. This process involves cancer cell detachment from the primary tumor, intravasation into the circulation, evasion of immune attack, extravasation at distant capillary beds and invasion and proliferation in distant organs. [1][2][3] In addition, the metastatic cells establish a microenvironment facilitating colonization (angiogenesis and further proliferation), resulting in macroscopic malignant secondary tumors.1-4 Metastatic cells preferentially invade those organs (lymph nodes, lung, liver, brain, bone, pleura and peritoneum) that promote tumor cell growth and survival consistent with the ''seed and soil'' hypothesis. 1,5,6 The metastatic and invasive potential of cancer cells is often correlated with abnormalities in phospholipids and in cell-surface glycolipids, which contribute to tumor progression.7-10 Hence, aberrant cellular migration and proliferation characterize the metastatic phenomenon.In this study, we analyzed the morphological, behavioral, biochemical and genetic properties of 3 n...

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Influence of methotrexate and cisplatin on tumor progression and survival in the VM mouse model of systemic metastatic cancer

Huysentruyt

Shelton

Seyfried

2009

Intl Journal of Cancer

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We recently identified a new tumor (VM-M3), which arose spontaneously in the brain of an inbred VM mouse. When grown outside the brain, the VM-M3 tumor expresses all major biological processes of metastasis to include local invasion, intravasation, immune system survival, extravasation, and secondary tumor formation involving lung, liver, kidney, spleen and brain. The VM-M3 tumor also expresses multiple properties of macrophage-like cells similar to those described previously in numerous human metastatic cancers suggesting that the VM-M3 model will be useful for studying most types of metastatic cancer, regardless of tissue origin. VM-M3 tumor cells, expressing firefly luciferase (VM-M3/Fluc), were grown subcutaneously in the immunocompetent and syngeneic VM mouse host. The antimetastatic effects of methotrexate (MTX; 25 mg/kg) and cisplatin (10-15 mg/kg) were evaluated following i.p. injections administered once/wk for 3 weeks. Bioluminescent imaging was used to measure VM-M3/Fluc growth and metastasis. All (12/12) control mice developed systemic cancer within 21 days of subcutaneous VM-M3/Fluc implantation. Although methotrexate did not inhibit VM-M3/Fluc primary tumor growth, it reduced lung and liver metastasis by 50% and completely inhibited metastasis to kidneys, spleen and brain. Cisplatin significantly reduced primary tumor growth, blocked metastasis to lung, liver, kidneys, spleen and brain, and significantly increased survival in all treated animals. Our findings show that the response of the VM-M3/Fluc tumor to MTX and cisplatin is similar to that reported in humans with metastatic disease. These findings indicate that the VM-M3/Fluc tumor is a reliable preclinical model for evaluating antimetastatic cancer therapies and underlying control pathways.Metastasis is the process by which cancer cells disseminate from the primary tumor, invade surrounding tissues and distant organs and is the primary cause of morbidity and mortality for cancer patients. 1,2 The metastatic cascade involves a series of sequential and interrelated steps to include cancer cell detachment from the primary tumor, intravasation into the circulation, evasion of immune attack, extravasation at a distant capillary bed and invasion and proliferation in distant organs. 2-5 Although many primary tumors can be treated with conventional therapies, few treatments are effective against metastatic disease. 1,5,6 Consequently, preclinical models that can accurately predict the therapeutic efficacy of antimetastatic drugs in patients would be useful for new drug development.The management of metastatic cancer can be improved with in vivo models that represent the complete pathophysiology of the human disease. 1,7-10 However, most available metastatic models including those that metastasize to brain have various shortcomings and limitations. For example, experimental metastatic models often require injection of tumor cells directly into the host's circulation, thus bypassing the early stages of metastasis before local invasion and intravasation...

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N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

Cited by 44 publications

References 41 publications

Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors

Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors

Metastatic cancer cells with macrophage properties: Evidence from a new murine tumor model

Influence of methotrexate and cisplatin on tumor progression and survival in the VM mouse model of systemic metastatic cancer

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