angiogenin and Uterine-Cervical-Neoplasms

To study the pharmacokinetics of neamine in rats and to evaluate its anti-cervical cancer activity.. The plasma level of neamine was determined by HPLC-ELSD. Pharmacokinetic parameters were calculated using DAS 2.0 software. Tissue microarray analysis was conducted to examine angiogenin (ANG) expression in normal and cancerous cervical tissues and to determine its correlation with clinical and pathologic presentations of cervical cancers. The anti-cervical cancer activity of neamine was assessed both in vitro and in vivo.. After intravenous (i.v.) administration of 15, 30, and 60 mg kg(-1) neamine, the pharmacokinetic parameters were as follows: AUC(0-t), 9,398.0 ± 653.4, 19,235.2 ± 2,939.0, and 35,437.7 ± 3,772.2 mg L(-1) min; C max, 170.8 ± 13.1, 353.3 ± 15.8, and 464.0 ± 33.1 mg L(-1); T 1/2, 34.9 ± 4.1, 46.8 ± 5.1, and 58.0 ± 12.5 min, respectively. The bioavailability of neamine administered through intramuscular, subcutaneous, intraperitoneal and intragastric route was 14.0 ± 3.0, 8.4 ± 0.6, 6.5 ± 3.3, and 3.1 ± 0.2 %, respectively. Up-regulated ANG expression and increased nuclear translocation were observed in cervical cancers as compared to normal cervical tissues. Moreover, upregulation of ANG was positively correlated with primary tumor invasion. Neamine inhibited ANG-induced HUVEC and HeLa cell proliferation as well as nuclear translocation of ANG. Consistently, neamine inhibited both the establishment and progression of xenograft human cervical cancers in athymic mice.. The bioavailability of neamine administered through extravascular routes was low. The half-life of neamine through i.v. administration was short. This suggests that a higher dosing frequency in order to maintain a therapeutic effect. Neamine holds potential against cervical cancer. The mechanisms of neamine inhibition are through blocking nuclear translocation of ANG thereby inhibiting both angiogenesis and cancer cell proliferation.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Area Under Curve; Biological Availability; Cell Proliferation; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Framycetin; Half-Life; HeLa Cells; Human Umbilical Vein Endothelial Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neovascularization, Pathologic; Rats; Rats, Sprague-Dawley; Ribonuclease, Pancreatic; Tissue Array Analysis; Up-Regulation; Uterine Cervical Neoplasms; Xenograft Model Antitumor Assays

Angiogenesis plays a key role in tumour growth and metastasis. Expression of angiogenic factors has been suggested as a marker for tumour malignity, and it may help to identify those patients with a poorer prognosis, aiding patient stratification for more aggressive and/or angiogenesis-targeted therapy. The present study examines the relationship between concentration of circulating angiogenic factors and clinical tumour criteria as well as patient survival.. A total of 125 patients with cervical cancer who underwent follow-up examinations between October 2002 and June 2005 were enrolled, and serum samples were examined for angiogenin, endoglin and endostatin by means of an ELISA. Concentrations were statistically correlated with clinical and outcome parameters.. Concentrations of all examined angiogenic factors were on average within the manufacturer-provided normal range. Both angiogenin and endostatin increased from non-invasive tumours through invasive lesions to recurrent disease, and endoglin showed an equally steady inverse trend; differences between non-invasive, invasive and recurrent stages of the disease were statistically significant. However it was not possible to determine a sufficiently selective cut-off point for either factor by receiver operating characteristic analysis, and there was no significant correlation with survival.. Angiogenic factors angiogenin, endoglin and endostatin show a definite relationship with disease stage in uterine cervical cancer, but are presently not suitable for use in risk stratification.

Topics: Antigens, CD; Biomarkers, Tumor; Endoglin; Endostatins; Enzyme-Linked Immunosorbent Assay; Female; Humans; Prognosis; Receptors, Cell Surface; Ribonuclease, Pancreatic; Uterine Cervical Neoplasms

Progression of cervical cancer is associated with excessive circulating levels of cytokines, which are known to be modulators of tumor angiogenesis. The concentrations of cytokines and growth factors were assayed using enzyme-linked immunosorbant assays in the serum of 61 women in various stages of cancer [stage 0 (n = 6), stage I (n = 15), stage II (n = 15), stage III (n = 15), and stage IV (n = 10)] and of 20 healthy control subjects. Our results indicated that b-FGF and TNF-beta levels were significantly elevated in stage I, and serum levels of TGF-beta and IL-7 were elevated in stages II-IV of invasive carcinoma. Our experimental subjects had significantly increased serum levels of IL-6, GM-CSF, and angiogenin in stages I-IV of cervical cancer, and TNF-alpha serum levels were elevated in all stages of invasive carcinoma. The serum levels of IL-8 and IL-10 were elevated only in stages II-III, and the levels of IL-2 were elevated in stages III-IV. The serum levels of IL-1 alpha and IL-1 beta remained unaltered in all stages of cancer progression. Progression of cervical cancer is associated with increased serum levels of angiogenin, IL-2, IL-6, IL-7, IL-8, IL-10, b-FGF TNF-alpha, TGF-beta, TNF-beta, and GM-CSF during different stages, all of which have the potential to be angiogenic amplifiers.

Topics: Adult; Cytokines; Female; Growth Substances; Humans; Interleukins; Middle Aged; Proteins; Ribonuclease, Pancreatic; Transforming Growth Factor beta; Uterine Cervical Neoplasms