angiogenin and Carcinoma

Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC-1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer.

Topics: Adult; Animals; Antibiotics, Antineoplastic; Carcinoma; Cell Line, Tumor; Cell Proliferation; Framycetin; Humans; Ki-67 Antigen; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Pancreatic Neoplasms; Platelet Endothelial Cell Adhesion Molecule-1; Ribonuclease, Pancreatic

To investigate whether elevated urinary levels of vascular endothelial growth factor (VEGF), carbonic anhydrase 9 (CA9), and angiogenin are associated with bladder cancer (BCa).. This was a case-control study in which voided urine samples from 127 patients (63 control subjects and 64 patients with BCa) were analyzed. The urinary concentrations of VEGF, CA9, angiogenin, and bladder tumor antigen (BTA) were assessed using enzyme-linked immunosorbent assays. We used the area under the curve of receiver operating characteristic curves to determine the ability of VEGF, CA9, and angiogenin to detect BCa in voided urine samples. Data were also compared with the findings from a commercial enzyme-linked immunosorbent assay-based BCa detection assay (BTA-Trak). The sensitivity, specificity, and positive and negative predictive values were calculated.. The urinary concentrations of VEGF, CA9, angiogenin, and BTA were significantly elevated in those with BCa. VEGF was the most accurate urinary biomarker (area under the curve 0.886, 95% confidence interval 0.8301-0.9418). Furthermore, multivariate regression analysis highlighted VEGF (odds ratio 5.90, 95% confidence interval 2.60-13.40, P < .0001) as an independent variable. The sensitivity and specificity for VEGF (83% sensitivity and 87% specificity) outperformed those for BTA (80% sensitivity and 84% specificity).. VEGF could be a valuable addition to voided urine sample analysis for the detection of BCa. Larger, prospective studies are needed to determine the clinical utility of urinary VEGF and angiogenin as biomarkers in the noninvasive evaluation of patients with BCa.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Area Under Curve; Biomarkers, Tumor; Carbonic Anhydrase IX; Carbonic Anhydrases; Carcinoma; Case-Control Studies; Confidence Intervals; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Ribonuclease, Pancreatic; ROC Curve; Urinary Bladder Neoplasms; Vascular Endothelial Growth Factor A; Young Adult

Further studies based on large series are necessary to investigate the role of MASPIN and angiogenin (ANG) in angiogenetic mechanisms of nasopharyngeal carcinoma (NPC) and their potential as prognostic markers.. NPC is a malignancy with an incidence among Caucasians of < 1 per 100 000 per year. In NPC, the aberrations of many pathways and the alteration in expression of several proteins have been reported. Tumor angiogenesis is the result of an imbalance between pro- and anti-angiogenic factors. MASPIN exerts several anti-tumor effects including inhibition of tumor-induced angiogenesis. ANG regulates angiogenesis under both physiological and pathological conditions supporting primary and metastatic tumor growth.. For the first time, we preliminarily investigated by immunohistochemistry the subcellular localization and expression of MASPIN, and the expression of ANG (in both carcinoma cells and intra-tumor vessels) and Ki-67 in 15 Caucasian patients with NPC treated with the same chemo-radiotherapeutic protocol.. MASPIN-positive NPCs had a prevalent cytoplasmic localization pattern. A trend towards significant direct correlation between MASPIN presence and disease-free survival (DFS) (p = 0.08) and a trend towards significant inverse correlation between ANG expression and DFS (p = 0.07) were found. An association between MASPIN presence and lower ANG expression in carcinoma cells was disclosed (statistical trend, p = 0.10).

Topics: Adult; Carcinoma; Female; Humans; Ki-67 Antigen; Male; Middle Aged; Nasopharyngeal Neoplasms; Prognosis; Ribonuclease, Pancreatic; Serpins; Treatment Outcome

Angiogenesis is a well known prerequisite for tumor growth and metastasis. It is believed that angiogenin initiates cell migration and aids cell proliferation. Based on this, the authors hypothesized that individuals who had increased plasma levels of angiogenin were at an elevated risk for carcinoma of the urinary bladder.. In this ongoing case-control study, the authors used an enzyme-linked immunosorbent assay to compare plasma levels of angiogenin in 209 patients with bladder carcinoma and in 208 healthy control participants who were matched according to age (+/- 5 years), gender, and ethnicity.. The mean plasma angiogenin concentration was significantly higher in patients compared with controls (343.2 ng/mL vs. 308.0 ng/mL, respectively; P < 0.01). High plasma angiogenin levels were associated with a two-fold increased risk for bladder carcinoma. Moreover, in patients who had superficial bladder carcinoma, plasma angiogenin levels were significantly higher among those who had recurrent disease than in those who were without recurrence (P < 0.01). Similarly, patients who had superficial bladder carcinoma with higher angiogenin levels had a shorter recurrence-free survival than patients who had lower angiogenin levels (P < 0.01). Finally, elevated angiogenin levels were associated with an increased recurrence risk, with hazard ratio of 2.85.. The results of this study demonstrated that the plasma levels of angiogenin were significantly higher in patients who had bladder carcinoma compared with healthy control participants and in patients with superficial bladder carcinoma who had recurrent disease compared with patients who were without recurrence. Therefore, an elevated plasma level of angiogenin may serve as a novel predictor for the risk of bladder carcinoma.

Topics: Biomarkers, Tumor; Carcinoma; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Ribonuclease, Pancreatic; Risk; Urinary Bladder Neoplasms

The progression of solid tumors is at least partly dependent on angiogenesis, the induction of which is mediated by several angiogenic factors, including angiogenin (ANG). The authors evaluated the expression of ANG in the tumor tissue and serum of patients with urothelial carcinoma.. The expression of ANG in 5 human bladder carcinoma cell lines and 24 urothelial carcinomas (10 superficial carcinomas and 14 invasive carcinomas) and in corresponding normal urothelial tissues was investigated by reverse transcriptase-polymerase chain reaction and Northern blot analysis. Serum levels of ANG in 52 healthy volunteers and in 135 patients with urothelial carcinomas (81 superficial carcinomas and 54 invasive carcinomas) were measured by using a sandwich enzyme immunoassay.. ANG mRNA transcripts were detected in all of the bladder carcinoma cell lines, urothelial carcinomas, and normal tissues. The mean level of ANG expression in invasive urothelial carcinomas was 4-fold higher than in superficial carcinomas and 5-fold higher than in normal tissues. The mean serum ANG concentration for invasive urothelial carcinoma patients (514.6+/-211.1 ng/mL) was significantly higher than for superficial urothelial carcinoma patients (381.7+/-169.3 ng/mL) and healthy volunteers (337.5+/-71.4 ng/mL). The overall survival rate of patients with elevated serum levels of ANG was significantly lower than that of patients with normal levels. Moreover, among the 47 patients with advanced urothelial carcinoma who underwent complete resection, the disease free survival rate of patients with elevated serum levels of ANG was significantly lower than that of patients with normal levels.. These results indicate that ANG is strongly expressed in the tumor tissue and is present in high levels in the serum of patients with invasive urothelial carcinoma compared with superficial carcinoma patients and that elevation of serum ANG level could be used as a novel predictor of the prognoses of patients with urothelial carcinoma.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; Disease Progression; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Prognosis; Protein Biosynthesis; Proteins; Ribonuclease, Pancreatic; Ureteral Neoplasms; Urinary Bladder Neoplasms

A noncytotoxic neutralizing monoclonal antibody (mAb), 26-2F, to human angiogenin (Ang), a potent inducer of neovascularization, has been reported to prevent or delay the establishment of HT-29 human tumor xenografts in athymic mice. In the present study the tumor model was modified to increase sensitivity to Ang antagonists to facilitate further investigations and comparisons of their capacity to inhibit tumor growth. An increase in the percentage of tumor-free mice from 10-25% to 65% is observed in this modified model after treatment with mAb 26-2F. An additional neutralizing mAb, 36u, that interacts with a different epitope on Ang similarly prevents the appearance of tumors, both alone and in combination with mAb 26-2F. In those tumors that develop in mice treated with these agents, the number of vascular elements is reduced. Actin, an Ang antagonist that unlike the mAbs binds both human and mouse Ang, also prevents the establishment of tumors while exhibiting no toxic effects at daily doses > 50 times the molar amount of circulating mouse Ang. Ang antagonists also inhibit the appearance of tumors derived from two other Ang-secreting human tumor cell lines--i.e., A549 lung adenocarcinoma and HT-1080 fibrosarcoma. These results demonstrate that inhibition of the action of Ang is an effective therapeutic approach for the treatment of malignant disease.

Topics: Actins; Angiogenesis Inducing Agents; Animals; Antibodies, Monoclonal; Carcinoma; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Interactions; Fibrosarcoma; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Neoplasms, Experimental; Proteins; Ribonuclease, Pancreatic; Survival Analysis