Antitumor effect of B16 melanoma cells genetically modified with the angiogenesis inhibitor RNasin

Botella‐Estrada, Rafael; Malet, Gema; Revert, Fernando; Dası́, Francisco; Crespo, Antonio; Sanmartín, O.; Guillén, C.; Aliño, Salvador F.

doi:10.1038/sj.cgt.7700302

Cited by 20 publications

(7 citation statements)

References 24 publications

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“…Tissue sections from RNasin-expressing cell tumors showed a lower number of blood vessels when compared to tissue sections from mice lungs that had been inoculated with control cell lines. The results of these experiments show that the genetic modification of tumor cells with RNasin cDNA yields a significant antitumor effect, and suggest that this effect is at least partially the result of angiogenesis inhibition (Botella-Estrada et al, 2001).…”

Section: Therapeutic Rolementioning

confidence: 86%

Angiogenesis in cutaneous melanoma: Pathogenesis and clinical implications

Srivastava

Ralhan

Kaur

2003

Microscopy Res & Technique

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Neovacularization is an essential step in the multistage progression of malignant melanoma. The onset of new blood vessel formation is ushered in by the release of VEGF and numerous other angiogenic molecules by the tumor cells. Human melanoma is unique among neoplasms that both avascular (early horizontal growth phase characterized by very slow progression and 99%, 10-year survival) and vascular (late radial and vertical growth phase associated with rapid growth, metastasis and death in many cases), phases are discernible by the naked eye. Although cell biologists have made great strides in unraveling the mechanisms involved in the laying down of tumor vasculature and the factors that inhibit it, clinicians treating melanoma have been rather slow to realize and utilize the full potential of suppressing the tumor blood flow to the best advantage of the patient. We suggest a consorted endeavor by all the melanoma experts across the globe to establish an "angiogenesis database" wherein they pool the blood flow and vascularity information along with Breslow's thickness, Clark's level of invasion, lymphatic and vascular invasion, regression, and outcome of their patients.

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Section: Therapeutic Rolementioning

confidence: 86%

Angiogenesis in cutaneous melanoma: Pathogenesis and clinical implications

Srivastava

Ralhan

Kaur

2003

Microscopy Res & Technique

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“…The labile nature of RI could have compounded the difficulty of correlating RI levels with physiological relevance. A recent study did, however, find that high RI levels decreased angiogenesis and tumor formation in mouse xenographs (83).…”

Section: A Expression Levels and Tissue Distributionmentioning

confidence: 86%

Ribonuclease Inhibitor: Structure and Function

Dickson

Haigis

Raines

2005

Progress in Nucleic Acid Research and Molecular Biology

193

218

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IntroductionThe mammalian ribonuclease inhibitor (RI) is a 50-kDa cytosolic protein that binds to pancreatic-type ribonucleases with femtomolar affinity and renders them inactive (for other reviews, see (1-5)). Complexes formed by RI and its target ribonucleases are among the tightest of known biomolecular interactions. The three-dimensional structure of RI is likewise remarkable, being characterized by alternating units of α-helix and β-strand that form a striking horseshoe shape (Fig. 1A) (6). The repeating structural units of RI possess a highly repetitive amino acid sequence that is rich in leucine residues (7,8). These leucine-rich repeats (LRRs) are present in a large family of proteins that are distinguished by their display of vast surface areas to foster protein protein interactions (9-12). The unique structure and function of RI have resulted in its emergence as the central protein in the study of LRRs, as well as its widespread use as a laboratory reagent to eliminate ribonucleolytic activity (13).The biological role of RI is not known in its entirety. The ribonucleases recognized by RI are secreted proteins, whereas RI resides exclusively in the cytosol. Nevertheless, RI affinity has been shown to be the primary determinant of ribonuclease cytotoxicity: only ribonucleases that evade RI can kill a cell (for reviews, see (14)(15)(16)(17)). In addition, the complex of RI with human angiogenin (ANG), which stimulates neovascularization by activating transcription in the nucleus (18,19), is the tightest of known RI·ribonuclease complexes. Yet, a role for RI in angiogenesis is not clear. Also intriguing are the 30-32 cysteine residues of RI, all of which must remain reduced for the protein to retain activity (20). These observations have lead researchers to hypothesize multiple biological roles for RI: (1) to protect cells from invading ribonucleases, (2) to regulate or terminate the activity of ribonucleases with known intracellular functions, and (3) to monitor the oxidation state of the cell in response to factors such as aging and oxidative stress. Here, we review the salient features of RI biochemistry and structure and thereby provide a context for examining the roles of RI in biology. I. Biochemical PropertiesThe inhibitory activity of RI in guinea pig liver extracts was discovered in 1952 (21). This activity was inactivated by proteases, heat, or sulfhydryl-group modification, and was sensitive to changes in pH (for a review, see (22)). In addition, the inhibitory activity was isolated in the supernatant fraction during a high-speed centrifugation, indicative of cytoplasmic localization. In the 1970's, techniques were developed to purify RI to homogeneity, enabling its biochemical characterization (23,2). Since then, RI has been isolated from numerous mammalian sources, including brain (24-26), liver (27,28,26), testis (29), and erythrocytes (30). A. PurificationRI is particularly abundant in mammalian placenta and liver, which have served as the major source of RI for purification. Human placenta...

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“…The empty pcDNA3m vector was utilized in the generation of the control cell line B16 pcDNA3 . Cells were transfected as previously described [20].…”

Section: Methodsmentioning

confidence: 99%