Effects of Hydroxyapatite Nanoparticles on Apoptosis and Invasion of Human Renal Cell Carcinoma 786-0 Cells

Renal cell carcinoma is the most common cancer of the kidney, and resistant to traditional therapies. The aim of this study is to investigate the effects of hydroxyapatite nanoparticles on human renal cell carcinoma 786-0 cells. Cell proliferation was assessed with an 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide(MTT) staining kit. The apoptosis assay was assessed with an FITC Annexin V Apoptosis Detection Kit. Caspase-3 and caspase-12 were detected by immunocytochemical staining and semi-qua...     

Suppression of hepatic tumor growth and metastasis by metronomic therapy in a rat model of hepatocellular carcinoma

Although continuous low-dose (metronomic [MET]) therapy exerts anti-cancer efficacy in various cancer models, the effect of long-term MET therapy for hepatocellular carcinoma (HCC) remains unknown. This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 wk. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve wk of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear antigen-positive cells and decreased hypoxia-inducible factor-1α levels and microvessel density. Lung metastases were detected in 100%, 80%, and 42.9% in the control, MTD, and MET groups, respectively. MET therapy significantly decreased expression of TIMP-1, MMP-2 and -9. For mediators of pro-MMP-2 activation, MET therapy induced significant suppression in the TIMP-2 and MMP-14 level. The survival in the MET group was significantly prolonged compared to the control and MTD groups. Long-term MET scheduling suppresses tumor growth and metastasis via its potent anti-angiogenic properties and a decrease in MMPs and TIMPs activities. These results provide a rationale for long-term MET dosing in future clinical trials of HCC treatment.     

Variations in the Concentrations of Cu and Zn and in the Ratio of Cu to Zn in Whole Blood and Hair Samples from Hepatocellular Carcinoma Patients and from Healthy Controls in Taiwan

An atomic absorption spectrophotometer was used to determine concentrations of copper and zinc and the ratio of Cu to Zn in samples of whole blood and hair from hepatocellular carcinoma (HCC) patients (n=51) and from healthy controls (n=50) in Taiwan. Our results indicate that the HCC patients have higher copper concentrations and higher ratios of Cu to Zn than do the healthy controls both in whole blood and hair samples, but only the concentration of copper and the ratio of Cu to Zn in whole blood were significantly different (p<0.001 and p<0.05). Conversely, a lower concentration of zinc was found in whole blood and hair samples of HCC patients. Similarly, only the concentration of zinc in whole blood showed a significant difference (p<0.001). We concluded that the whole blood concentrations of copper and zinc and the ratio of Cu to Zn seemed to have a higher correlation with HCC. Thus, we suggest that a sample of whole blood may be a more suitable diagnostic sample than is a hair sample for HCC.     

Modelling the Recurrence of Bladder Cancer

The risk of a new tumor recurrence after transurethral resection (surgical operation) in patients with primary superficial bladder carcinoma is evaluated. As the exact time of the event is not known, it is suggested to consider interval-censored survival data methodology. We use the model of Farrington to perform a prognostic model for predicting a new recurrence and to determine the clinicopathologic factors associated within interval-censored data framework. The implementation of this method is easy using standard statistical packages. Anyway, we use diagnostic methods for the validation of the model developed by the same author for interval-censored data. The obtained model is easily interpretable and let us to individualize the course of follow-up and treatment of each patient in order to improve the patient’s quality of life.      

Using Gd-EOB-DTPA-enhanced 3-T MRI for the differentiation of infiltrative hepatocellular carcinoma and focal confluent fibrosis in liver cirrhosis

Purpose

The purpose of the study was to determine significant imaging features to differentiate between infiltrative hepatocellular carcinoma (HCC) and confluent fibrosis (CF) in liver cirrhosis using Gd-EOB-DTPA-enhanced 3-T magnetic resonance imaging.

Material and methods

Nineteen infiltrative HCCs and eight CFs were included. We evaluated the difference in imaging findings and apparent diffusion coefficient (ADC) between the two entities. We compared T2-weighted image (WI) and hepatobiliary phase (HBP) in terms of the clarity of the lesion outer margin.

Results

Seventeen infiltrative HCCs showed lobulated margin, while focal CFs showed either straight (n = 3) or irregular margins (n = 5) (P = .001). All infiltrative HCCs had intact or bulging contours, and all focal CFs showed capsular retraction (P = .001). Fourteen infiltrative HCCs and two focal CFs showed arterial enhancement (P = .035). The ADC of infiltrative HCCs was significantly lower than that of CFs (P = .001). Satellite nodules were noted in 10 infiltrative HCCs. In terms of outer margin clarity, infiltrative HCCs showed a more distinct margin on HBP than on T2-WI (P = .005), while these two sequences were not significantly different in focal CFs (P = 1.000).

Conclusion

HBP improved the imaging characteristics of infiltrative HCC, allowing it to be distinguished from focal CF. Infiltrative HCC showed lower ADC values than focal CF. Lobular configuration, contour bulging, enhancement pattern, associated satellite nodules and portal vein thrombosis were still found to be highly suggestive MR findings for infiltrative HCC.     

Magnetic resonance imaging of mouse Ehrlich carcinoma growth inhibition by thiacarpine, an analogue of cytotoxic marine alkaloid polycarpine

The anticancer effect of thiacarpine, a synthetic analogue of the known cytotoxic alkaloid polycarpine isolated from the Pacific ascidian Polycarpa aurata, was investigated in vivo in experiments using mouse solid Ehrlich carcinoma tumor as the target. A high-resolution magnetic resonance imaging (MRI) technique using a MR tomograph "PharmaScan" US70/16 (Bruker, Ettlingen, Germany) was used for visualization and quantification of tumor size. Fluorescence microscopy and image analysis were applied to determine Ehrlich carcinoma cell chromatin condensing (apoptosis) and necrosis in Ehrlich carcinoma cells at the action of thiacarpine in in vitro experiments. The scan and size calculations of the tumor and some mouse organs were carried out during the experiments. Thiacarpine in a total dose of 100 mg/kg was found to exhibit the delay in growth of the mouse tumor. The antineoplastic effect of this compound was accompanied by an increase in the lifetime of experimental mice in comparison with the control group of animals. Our data show that the ability of thiacarpine to induce apoptosis in carcinoma cells may contribute to thiacarpine anticancer effects against mice solid Ehrlich carcinoma in vivo detected by MRI.     

Treatment activity of a mixed-ligand coordination polymer on gastric carcinoma

Reaction of 4,4′,4″-nitrilotribenzoic acid (H₃L), a C₃-symmetric ligand, with the divalent Co(II) salt Co(NO₃)₂·6H₂O in the present of the N-donor ligand 1,2-di(4-pyridyl)ethylene (DPE) affords a new mixed-ligand coordination polymer with the chemical formula of [Co₃(TNB)(DPE)₂]·2H₂O·DMF (1). In this study, CCK-8 assay was used to determine the effect of novel compound on proliferation of gastric cancer cells. The VEGF signaling pathway in gastric cancer cells was determined through employing real-time PCR after treatment of the above complex. Further, molecular docking simulation confirmed that the biological activity was coming from the carboxyl groups through the hydrogen bonding interactions with the receptor protein, the pyridine group only bonded with the Co ion for the formation of the Co complex.     

Volatile organic compounds in head and neck squamous cell carcinoma—An in vitro pilot study

Owing to the lack of specific symptoms, diagnosis of head and neck squamous cell carcinoma (HNSCC) may be delayed. We evaluated volatile organic compounds in tumor samples from patients suffering from HNSCC and tested the hypothesis that there is a characteristic altered composition in the headspace of HNSCC compared with control samples from the same patient with normal squamous epithelium. These results provide the basis for future noninvasive breath analysis in HNSCC. Headspace air of suspected tumor and contralateral control samples in 20 patients were analyzed using ion-mobility spectrometry. Squamous cell carcinoma was diagnosed in 16 patients. In total, we observed 93 different signals in headspace measurements. Squamous cell carcinomas revealed significantly higher levels of volatile cyclohexanol (0.54 ppb_v, 25th to 75th percentiles 0.35–0.86) compared with healthy squamous epithelium (0.24 ppb_v, 25th to 75th percentiles 0.12–0.3; p < 0.001). In conclusion, head and neck squamous cell carcinoma emitted significantly higher levels of volatile cyclohexanol in headspace compared with normal squamous epithelium. These findings form the basis for future breath analysis for diagnosis, therapy control and the follow-up of HNSSC to improve therapy and aftercare.