Effect of Melilotus officinalis extract on the apoptosis of brain tissues by altering cerebral thrombosis and inflammatory mediators in acute cerebral ischemia.

Present investigation evaluates the protective effect of Melilotus officinalis (MO) extract on the brain tissues in acute cerebral ischemia. Acute cerebral ischemia was induced by occlusion of carotid artery and rats with cerebral ischemia were treated with MO (100, 250 & 500mg/kg) for the duration of three days. Cerebral ischemia was confirmed by estimating infract volume and neurological deficit score. Moreover biochemical parameters in plasma such as 6-keto-PGF1α and TXB2 and concentration of cytokine, oxidative stress, apoptosis ratio and protein expressions of Bcl2 & Bax were estimated in the brain tissues. It was observed that treatment with MO significantly (p<0.01) decreases the infract volume and neurological deficit score than negative control group. There was significant decrease (p<0.01) in the oxidative stress and cytokine in the brain tissues and increase in the plasma concentration of 6-keto-PGF1α in MO treated group of rats compared to negative control group. Plasma concentration of TXB 2 was significantly enhanced in MO treated group compared to negative control group of rats. It was also found that treatment with MO ameliorates the apoptosis induced by cerebral ischemia. Present study concludes that MO ameliorates apoptosis of brain tissues in cerebral ischemic rats by decreasing cerebral thrombosis, oxidative stress and inflammatory mediators.

Phase 1 trial of tivantinib in combination with sorafenib in adult patients with advanced solid tumors.

PURPOSE: This phase I study evaluated the safety, tolerability, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of tivantinib combined with sorafenib in patients with advanced solid tumors. MATERIALS AND METHODS: A standard 3 + 3 dose escalation design was used. At the RP2D, expansion cohorts in 5 tumor types could be enrolled. Pharmacogenetic and pharmacodynamic analysis were performed. RESULTS: Eighty-seven patients received the study treatment. The combination had no unexpected toxicities. The most common treatment-related adverse events (AE) were rash (40 %), diarrhea (38 %), and anorexia (33 %). The RP2D was tivantinib 360 mg BID and sorafenib 400 mg BID for all cancer histologies, except in hepatocellular carcinoma (HCC) patients tivantinib was 240 mg BID plus sorafenib 400 mg BID. The overall response rate was 12 % in all patients, 26 % in melanoma, 15 % in renal cell carcinoma (RCC), 10 % in HCC, and 0 % in other patients. Disease control rate (CR, PR and SD ≥8 weeks) was 58 % in all patients, 90 % in RCC, 65 % in HCC, 63 % in melanoma, 40 % in breast cancer, and 8 % in NSCLC patients. CONCLUSIONS: The combination treatment could be administered at full standard single-agent doses in all patients except those with HCC, where tivantinib was lowered to 240 mg BID. Preliminary evidence of anticancer activity was observed in patients with RCC, HCC, and melanoma, including patients refractory to sorafenib and/or other anti-VEGF pathway therapies. The combination treatment has therapeutic potential in treating a variety of solid tumors.

Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction.

The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection).

[Study of relationship between powder-size gradation and mechanical properties of Zirconia toughened glass infiltrated nanometer-ceramic composite powder].

OBJECTIVE: The fabrication of all-ceramic dental restorations is challenged by ceramics' relatively low flexural strength and intrinsic poor resistance to fracture. This paper aimed at investigating the relationships between powder-size gradation and mechanical properties of Zirconia toughened glass infiltrated nanometer-ceramic composite (Al(2)O(3)-nZrO(2)). METHODS: Al(2)O(3)-nZrO(2) ceramics powder (W) was processed by combination methods of chemical co-precipitation and ball milling with addition of different powder-sized ZrO(2). Field-emission scanning electron microscopy was used to determine the particle size distribution and characterize the particle morphology of powders. The matrix compacts were made by slip-casting technique and sintered to 1,450 degrees C and flexural strength and the fracture toughness of them were measured. RESULTS: 1. The particle distribution of Al(2)O(3)-nZrO(2) ceramics powder ranges from 0.02 - 3.5 micro m and among them the superfine particles almost accounted for 20%. 2. The ceramic matrix samples with addition of nZrO(2) (W) showed much higher flexural strength (115.434 +/- 5.319) MPa and fracture toughness (2.04 +/- 0.10) MPa m(1/2) than those of pure Al(2)O(3) ceramics (62.763 +/- 7.220 MPa; 1.16 +/- 0.02 MPa m(1/2)). CONCLUSIONS: The particle size of additive ZrO(2) may impose influences on mechanical properties of Al(2)O(3)-nZrO(2) ceramics matrix. Good homogeneity and reasonable powder-size gradation of ceramic powder can improve the mechanical properties of material.