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1. Cyran CC, Fu Y, Raatschen HJ, Rogut V, Chaopathomkul B, Shames DM, Wendland MF, Yeh BM, Brasch RC: New macromolecular polymeric MRI contrast agents for application in the differentiation of cancer from benign soft tissues. J Magn Reson Imaging; 2008 Mar;27(3):581-9
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  • [Title] New macromolecular polymeric MRI contrast agents for application in the differentiation of cancer from benign soft tissues.
  • PURPOSE: To compare three new macromolecular polyethylene glycol (PEG) -core dendrimeric gadolinium(Gd)-based MRI contrast agents for their applicability in quantitative assays of endothelial leakiness and tissue vascular density for the differentiation of cancer from normal soft tissues.
  • MATERIALS AND METHODS: Thirty-two athymic rats with human breast cancer xenografts (MDA-MB-435) were imaged by dynamic MRI following enhancement with one of three new (Gd-DOTA)-conjugated PEG-core dendrimer contrast agents (effective molecular weights 161 to 323 kDa).
  • Results were compared with a prototype macromolecular contrast agent, albumin (Gd-DTPA).
  • 100 cm(3)) and tumor fractional plasma volumes (%) based on a two-compartment kinetic model were performed for skeletal muscle and tumors.
  • RESULTS: The largest PEG-core contrast agent, PEG(20,000)-Gen4-(Gd-DOTA), leaked in breast tumors (K(PS) = 50 +/- 23 microL/min .
  • 100 cm(3)) in normal soft tissue microvessels allowing successful differentiation (P < 0.05) of cancers from normal muscle.
  • PEG(12,000)-Gen4-(Gd-DOTA) leaked in tumors and in normal muscle (K(PS) = 51 +/- 26 and K(PS) = 21 +/- 18 microL/min .
  • The smallest agent, PEG(12,000)-Gen3-(Gd-DOTA) also showed a measurable leak in both normal and malignant microvessels.
  • CONCLUSION: MRI assays of vascular endothelial leakiness using new PEG-core, (Gd-DOTA)-conjugated macromolecular contrast agents proved applicable for the differentiation of human breast cancer from normal soft tissue.
  • The apparent threshold in effective molecular weight for a clear differentiation of cancer from normal muscle with no measurable leak in the muscle is between 194 and 323 kDa.
  • [MeSH-minor] Animals. Breast Neoplasms / diagnosis. Endothelium, Vascular. Female. Humans. Neoplasm Transplantation. Rats. Rats, Nude. Transplantation, Heterologous

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  • (PMID = 18219614.001).
  • [ISSN] 1053-1807
  • [Journal-full-title] Journal of magnetic resonance imaging : JMRI
  • [ISO-abbreviation] J Magn Reson Imaging
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 082923; United States / NCI NIH HHS / CA / R01 CA 103850
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Contrast Media; 0 / Heterocyclic Compounds; 0 / Organometallic Compounds; 92923-44-9 / gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; AU0V1LM3JT / Gadolinium
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2. Zhou NK, Zheng ML, Luo CH, Liang CY, Liu X, Liu Y, Sun YE: [An experimental research on inhibitory action of skeletal muscle conditioned medium on metastases of lung carcinomas]. Ai Zheng; 2003 Mar;22(3):274-6
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  • [Title] [An experimental research on inhibitory action of skeletal muscle conditioned medium on metastases of lung carcinomas].
  • BACKGROUND & OBJECTIVE: Malignant tumors spread and metastasize in the majority of the organs, but are very rare in skeletal muscles.
  • This study was conducted to explore the effect of organic microenvironment of skeletal muscles on the proliferation of pulmonary large cell carcinomas with different metastatic potential and to investigate the mechanism of the rarity of metastases in skeletal muscles.
  • METHODS: Primary culture of newborn Wistar rat skeletal muscle cells was established, and the murine skeletal muscle conditioned medium(MMCM)was prepared to test its effect in vitro on pulmonary large cell carcinomas with different metastatic potential (PLA-801C with lower potential and PLA-801D with relatively higher potential) by MTT assay.
  • Adriamycin was used as positive control for MMCM; murine benign renal cells BHK-21 were used as negative control for lung carcinoma cells.
  • RESULTS: Proliferation of tumor cell lines of both PLA-801C and PLA-801D was significantly restrained when cultured with MMCM, while BHK-21 cells were not affected(P< 0.05).
  • CONCLUSION: Skeletal muscle cells could selectively inhibit the proliferation of cancerous cells in vitro while benign cells are not affected.
  • Tumor cells with higher metastatic potential are more sensitive to this effect.
  • [MeSH-major] Carcinoma, Large Cell / pathology. Culture Media, Conditioned / pharmacology. Lung Neoplasms / pathology. Muscle, Skeletal / chemistry
  • [MeSH-minor] Animals. Cell Division / drug effects. Cell Extracts / pharmacology. Humans. Mice. Neoplasm Metastasis. Rats. Rats, Wistar. Tumor Cells, Cultured

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  • (PMID = 12654185.001).
  • [Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer
  • [ISO-abbreviation] Ai Zheng
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Cell Extracts; 0 / Culture Media, Conditioned
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3. Fan X, Medved M, River JN, Zamora M, Corot C, Robert P, Bourrinet P, Lipton M, Culp RM, Karczmar GS: New model for analysis of dynamic contrast-enhanced MRI data distinguishes metastatic from nonmetastatic transplanted rodent prostate tumors. Magn Reson Med; 2004 Mar;51(3):487-94
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  • Dynamic contrast-enhanced MRI (DCEMRI) data were acquired from metastatic and nonmetastatic tumors in rodents to follow the uptake and washout of a low-molecular-weight contrast agent (Gd-DTPA) and a contrast agent with higher molecular weight (P792).
  • The concentration vs. time curves calculated for the tumor rims and centers were analyzed using the two-compartment model (TCM) and a newly developed empirical mathematical model (EMM).
  • Parameters derived from the empirical model showed that the contrast agent washout rate was significantly slower in metastatic tumors than in nonmetastatic tumors for both Gd-DTPA (P < 0.03) and P792 (P < 0.04).
  • The effects of the tumor on blood flow in "normal" tissue immediately adjacent to the tumors were evident: Gd-DTPA uptake and washout rates were much lower in muscle near the tumor (P < 0.05) than normal muscle farther from the tumor.
  • The results suggest that accurate fits of DCEMRI data provide kinetic parameters that distinguish between metastatic and relatively benign cancers.
  • [MeSH-major] Contrast Media. Image Enhancement. Magnetic Resonance Imaging. Muscle Neoplasms / secondary. Muscle, Skeletal / surgery. Neoplasm Transplantation / pathology. Prostatic Neoplasms / pathology
  • [MeSH-minor] Animals. Gadolinium DTPA. Male. Models, Biological. Molecular Weight. Rats. Time Factors. Tumor Cells, Cultured

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  • [Copyright] Copyright 2004 Wiley-Liss, Inc.
  • (PMID = 15004789.001).
  • [ISSN] 0740-3194
  • [Journal-full-title] Magnetic resonance in medicine
  • [ISO-abbreviation] Magn Reson Med
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R21 CA089408-01A1
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Contrast Media; K2I13DR72L / Gadolinium DTPA
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4. Takeuchi T, Heng HH, Ye CJ, Liang SB, Iwata J, Sonobe H, Ohtsuki Y: Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma. Am J Pathol; 2003 Oct;163(4):1395-404
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  • Northern blot analysis revealed that the 3.2-kb skeletrophin mRNA was expressed in normal skeletal muscle, and to a lesser extent in heart, brain, and kidney.
  • To better understand the biological properties of skeletrophin, we used a yeast two-hybrid system to screen for molecules interacting with skeletrophin and found that skeletrophin bound to actin monomer.
  • Fluorescence in situ hybridization mapped the skeletrophin gene on human chromosome 1p36.2-36.3, in which putative tumor suppressor genes for malignant melanoma have been postulated to exist.
  • We therefore immunohistochemically stained benign nevi and malignant melanoma tissues.
  • Notably, 23 of 25 benign nevi expressed skeletrophin in cytoplasm, but 18 of 38 cases of primary skin melanoma appeared to lack skeletrophin expression.
  • Treatment with a demethylating agent, 5'-aza-2-deoxycytidine, restored skeletrophin expression in cultured Mewo melanoma cells.
  • [MeSH-major] Actins / metabolism. Azacitidine / analogs & derivatives. Melanoma / metabolism. Microfilament Proteins / genetics. Microfilament Proteins / metabolism. Neoplasm Proteins / genetics. Neoplasm Proteins / metabolism
  • [MeSH-minor] Amino Acid Sequence / genetics. Blotting, Northern. Blotting, Western. Cloning, Molecular. DNA, Complementary / genetics. Down-Regulation. Humans. Immunohistochemistry / methods. In Situ Hybridization, Fluorescence. Molecular Sequence Data. Precipitin Tests. Reverse Transcriptase Polymerase Chain Reaction. Staining and Labeling. Transfection. Tumor Cells, Cultured. Two-Hybrid System Techniques. Ubiquitin-Protein Ligases. Yeasts

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  • (PMID = 14507647.001).
  • [ISSN] 0002-9440
  • [Journal-full-title] The American journal of pathology
  • [ISO-abbreviation] Am. J. Pathol.
  • [Language] eng
  • [Databank-accession-numbers] GENBANK/ AB074480
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Actins; 0 / DNA, Complementary; 0 / Microfilament Proteins; 0 / Neoplasm Proteins; 776B62CQ27 / decitabine; EC 6.3.2.19 / MIB2 protein, human; EC 6.3.2.19 / Ubiquitin-Protein Ligases; M801H13NRU / Azacitidine
  • [Other-IDs] NLM/ PMC1868282
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