Relationship Between Serum Concentrations of the Growth Factor Pleiotrophin and Pleiotrophin-Positive Tumors

Souttou, Boussad; Juhl, Hartmut; Hackenbruck, Joannah; Röckseisen, Marianne; Klomp, H.-J.; Raulais, Daniel; Vigny, Marc; Wellstein, Anton

doi:10.1093/jnci/90.19.1468

Cited by 74 publications

(88 citation statements)

References 19 publications

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“…[1,2,4] Therefore, various carcinomas express MK, and serum MK level increases in some carcinomas including hepatocellular carcinoma and gastrointestinal carcinomas. [11][12][13] In the present study, there was no difference in positive rate or intensity of MK expression between benign odontogenic tumors and their malignant counterparts (Table 2). These data suggest that MK cannot be used as a marker to distinguish malignant from nonmalignant [9] investigated MK expression in tooth development of mice and found that the distribution of MK expression depended on the developmental stage of the tooth germ.…”

Section: Discussionmentioning

confidence: 39%

Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors

et al. 2008

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Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors AbstractMidkine (MK; a low molecular weight heparin-binding growth factor) is a multifunctional cytokine. MK plays a role in morphogenesis of many organs including teeth through epithelial-mesenchymal interactions. We immunohistochemically examined MK expression in various human odontogenic tumors. There was no difference in positive rate and intensity of MK between benign odontogenic tumors and their malignant counterparts.Ameloblastoma showed MK localization in the peripheral columnar cells in budding processes from the parenchyma, which frequently expressed proliferating cell nuclear antigen (PCNA). MK was also preferentially expressed in keratinized cells in acanthomatous ameloblastoma and keratocystic odontogenic tumor. In odontogenic mixed tumors except for odontoma, intense immunoreactivity to MK was found in epithelial follicles, the surrounding odontogenic ectomesenchymal tissue, and the basement membrane between them. Intensity in the odontogenic ectomesenchyme decreased in relation to distance from the epithelial follicles. No expression was found in tumor cells associated with production of dental hard tissues in odontogenic mixed tumors including odontoma. These findings suggested that MK is involved in the reciprocal interaction between odontogenic epithelium and odontogenic ectomesenchymal tissue in areas without dental hard tissue formation in odontogenic mixed tumors. Co-expression of MK and PCNA was also observed in epithelial follicles and highly cellular nodules in the 3 ectomesenchyme of odontogenic mixed tumors. MK is considered to mediate growth activity of odontogenic tumors and cell differentiation of odontogenic mixed tumors through molecular mechanisms similar to those involved in morphogenesis of the tooth.Abbreviations: MK, midkine; PCNA, proliferating cell nuclear antigen 4

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Section: Discussionmentioning

confidence: 39%

Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors

et al. 2008

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“…Additionally, determination of intratumoral PTN levels by ELISA 29 showed a 450% down-regulation of PTN upon Rz66-PTN treatment as compared to the control ribozyme group (Figure 5b) indicating high ribozyme bioactivity. Taken together, our findings in both experiments demonstrate marked ribozyme-mediated reduction of PTN expression and consecutive impairment of tumor growth and tumor integrity in vivo.…”

Section: Ribozymes and Gene Expressionmentioning

confidence: 96%

“…For the determination of PTN levels, tumor samples were homogenized in 200 ml Tris-buffered saline/0.5% Tween-20, and after centrifugation, supernatants were diluted 1:10 in the same buffer. The PTN ELISA was performed as described previously 29 with recombinant PTN as standard, and total protein concentration was determined using the D c Protein Assay from Bio-Rad (Hercules, CA, USA). Values were tested for normal distribution and statistical significances were evaluated by Student's t-test.…”

Section: Synthesis Of Lmw-pei Preparation Of Lmw-pei/rna and Lmw-peimentioning

confidence: 99%

Delivery of unmodified bioactive ribozymes by an RNA-stabilizing polyethylenimine (LMW-PEI) efficiently down-regulates gene expression

et al. 2002

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The sequence-specific cleavage of RNA molecules through ribozyme targeting is particularly attractive since it allows the effective abrogation of protein expression. So far, however, use of enzymatically active RNA molecules (ribozymes) has, without chemical modification, been severely hampered by ribozyme instability and poor cellular uptake. In this paper, we present a method for protection and cellular delivery of ribozymes by complexation with a low molecular weight polyethylenimine (LMW-PEI). We show that LMW-PEI almost completely stabilizes ribozymes or any RNA against degradation in vitro. Upon their highly efficient cellular uptake, non-toxic LMW-PEI-complexed ribozymes display intracellular bioactivity already at low concentrations as demonstrated by down-regulation of two different genes in different cell lines. In vivo, LMW-PEI-complexed ribozymes were stabilized after intraperitoneal (i.p.) injections, showed prolonged circulation time and intact ribozymes were detected in the subcutaneous (s.c.) tumor mass 60 min after the injection. In addition, i.p. injections of LMW-PEI-complexed ribozymes targeted against the growth factor pleiotrophin (PTN) resulted in marked reduction of s.c. human melanoma tumor growth and of intratumoral PTN levels in a mouse xenograft model. Thus, this paper describes a novel method for exogenous delivery of any bioactive RNA ribozyme in vitro and in vivo without chemical modification.

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“…Elevated PTN expression has been shown to occur in malignant tumours with respect to normal tissue, for example in ovarian carcinoma, and in tumour cell lines such as breast carci-noma and glioblastoma Nakanishi et al, 1997). A recent study investigated PTN in the serum of patients with various cancers and the results indicated that PTN is associated with the presence of tumour (Souttou et al, 1998;Kuroi and Toi, 2001).…”

mentioning

confidence: 99%

“…In the present study we have evaluated the serum concentration of PTN in patients with lung cancer in comparison with a control group of healthy subjects, using a modified highly sensitive enzyme-linked immunosorbent assay (Souttou et al, 1998). Furthermore, we compared the serum concentration of PTN in these patients with the plasma concentration of the classical angiogenic growth factor, VEGF, with respect to disease staging and response to therapy.…”

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confidence: 99%

Serum levels of the angiogenic factor pleiotrophin in relation to disease stage in lung cancer patients

et al. 2002

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Pleiotrophin is a heparin-binding growth factor involved in the differentiation and proliferation of neuronal tissue during embryogenesis, and also secreted by melanoma and breast carcinoma cells. Pleiotrophin exhibits mitogenic and angiogenic properties and has been shown to influence the vascular supply, expansion and metastasis of tumour cells. Our aim was to study the serum and plasma concentrations of pleiotrophin and the classical angiogenic growth factor vascular endothelial growth factor. Using a specific ELISA-test we studied patients with small cell lung cancer (n=63), and patients with non-small cell lung cancer (n=22) in comparison to healthy control subjects (n=41). In most of the lung cancer patients (81%), we found serum levels of pleiotrophin above those of control subjects (P50.001). Of the 63 small cell lung cancer patients in the study pleiotrophin serum levels were elevated in 55 cases (87%) and in 14 cases (63%) of the 22 non-small cell lung cancer patients. Pleiotrophin mean serum concentrations were 10.8-fold higher in the tumour patient group as compared to the control group (P50.001). Furthermore, pleiotrophin serum levels correlated positively with the stage of disease and inversely with the response to therapy. Plasma vascular endothelial growth factor concentrations were elevated in only in 28.6% of small cell lung cancer and 45.5% of non-small cell lung cancer patients by an average of 2.3-fold. Quite strikingly, there was no apparent correlation between the plasma vascular endothelial growth factor concentration and the stage of disease. Our study suggests that pleiotrophin may be an early indicator of lung cancer and might be of use in monitoring the efficacy of therapy, which needs to be confirmed by larger studies.

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Relationship Between Serum Concentrations of the Growth Factor Pleiotrophin and Pleiotrophin-Positive Tumors

Abstract: Elevated serum pleiotrophin levels can indicate the presence of tumors expressing this factor. Monitoring serum levels of pleiotrophin may prove useful in determining the pharmacologic efficacy of cytotoxic or anti-pleiotrophin therapy.

Cited by 74 publications

References 19 publications

Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors

Midkine expression correlating with growth activity and tooth morphogenesis in odontogenic tumors

Delivery of unmodified bioactive ribozymes by an RNA-stabilizing polyethylenimine (LMW-PEI) efficiently down-regulates gene expression

Serum levels of the angiogenic factor pleiotrophin in relation to disease stage in lung cancer patients

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