Cartilage is one of the very few naturally occurring avascular tissues where lack of angiogenesis is the guiding principle for its structure and function. This has attracted investigators who have sought to understand the biochemical basis for its avascular nature, hypothesising that it could be used in designing therapies for treating cancer and related malignancies in humans through antiangiogenic applications. Cartilage encompasses primarily a specialised extracellular matrix synthesised by chondrocytes that is both complex and unique as a result of the myriad molecules of which it is composed. Of these components, a few such as thrombospondin-1, chondromodulin-1, the type XVIII-derived endostatin, SPARC (secreted protein acidic and rich in cysteine) and the type II collagen-derived N-terminal propeptide (PIIBNP) have demonstrated antiangiogenic or antitumour properties in vitro and in vivo preclinical trials that involve several complicated mechanisms that are not completely understood. Thrombospondin-1, endostatin and the shark-cartilage-derived Neovastat preparation have also been investigated in human clinical trials to treat several different kinds of cancers, where, despite the tremendous success seen in preclinical trials, these molecules are yet to show success as anticancer agents. This review summarises the current state-of-the-art antiangiogenic characterisation of these molecules, highlights their most promising aspects and evaluates the future of these molecules in antiangiogenic applications.

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Antiangiogenic and anticancer molecules in cartilage.

OBJECTIVE Endostar® (Rh-endostatin injection) is a new recombinant human endostatin developed by Shandong Simcere-Medgenn Bio-Pharmaceutical Co., Ltd in China. This study was performed to evaluate the efficacy and safety of Endostar plus leucovorin calcium/ 5-fluorouracil/oxaliplatin (FOLFOX4) in treating patients with advanced colorectal cancer. METHODS Thirty-six patients with advanced colorectal cancer were retrospectively assigned to one of two treatment groups: FOLFOX4 (control) or FOLFOX4 plus Endostar (Endostar) according to patient accreditation. The observational end points were overall response rate, overall survival, progression-free survival and toxicity. RESULTS The response rate and progression-free survival of Endostar were significantly better than those of control group (P <0.05), but significance was not observed for median survival. In addition, gastrointestinal side effects and incidence of leucopenia were not lower than in the control group (P<0.05). CONCLUSIONS The addition of Endostar to FOLFOX4 resulted in a higher objective response rate and longer time to disease progression. Hypertension and cardiac ischemia were the principal safety concerns, but were manageable. Endostar deserves to be further investigated by randomized controlled clinical trails.

Clinical observation of Endostar® combined with chemotherapy in advanced colorectal cancer patients.

Objective To observe the efficacy, side effects and impact on the quality of life of Aidi Injection combined with leucovorin calcium/5-fluorouracil/oxaliplatin (FOLFOX4 regimen) in the treatment of advanced colorectal cancer patients. Methods A consecutive cohort of 100 patients were divided into two groups: the experimental group was treated with Aidi injection and FOLFOX4 while the control group was only administered FOLFOX4. After more than two courses of treatment, efficacy, quality of life and side effects were evaluated. Results The response rate of experimental group was not significantly different with that of control group (P>0.05), but differences were significant in clinical benefit response and KPS score. Iin addition, gastrointestinal reaction and the incidence of leukopenia were lower than that of control group (P Conclusions Aidi injection combined with FOLFOX4 is associated with reduced toxicity of chemotherapy, enhanced clinical benefit response and improved quality of life of patients with advanced colorectal cancer. Aidi injection deserves to be further investigated by randomized control clinical trails.

A clinical study on safety and efficacy of Aidi injection combined with chemotherapy.

Objective: To observe the efficacy, side effects and impact on the quality of life of Aidi Injection® combined with leucovorin calcium/ 5-fluorouracil/ oxaliplatin (FOLFOX4 regimen) in the treatment of advanced colorectal cancer patients. Methods: A consecutive cohort of 100 patients were divided into two groups: the experimental group was treated with Aidi injection and FOLFOX4 while the control group was only administered FOLFOX4. After more than two courses of treatment, efficacy, quality of life and side effects were evaluated. Results: The response rate of experimental group was not significantly different with that of control group (P>0.05), but differences were significant in clinical benefit response and KPS score. Iin addition, gastrointestinal reaction and the incidence of leukopenia were lower than that of control group (P<0.05). Conclusions: Aidi injection combined with FOLFOX4 is associated with reduced toxicity of chemotherapy, enhanced clinical benefit response and improved quality of life of patients with advanced colorectal cancer. Aidi injection deserves to be further investigated by randomized control clinical trails.

RESEARCH COMMUNICATION A Clinical Study on Safety and Efficacy of Aidi Injection ® Combined with Chemotherapy

Effects of endostar combined multidrug chemotherapy in osteosarcoma.

Purpose Endostar is a proteolytic fragment of collagen XVIII that has been shown to have antitumor activity, with a favorable toxicological profile. We conducted this study to investigate its efficacy and safety when combined with chemotherapy in patients with advanced solid tumors. Methods From July 2006 to September 2008, 45 patients with histologically or cytologically confirmed solid tumors were enrolled into this study. All received Endostar at a dose of 7.5 mg/m2 /day as an intravenous infusion for more than 7 days, in combination with chemotherapy. Patients were treated until tumor progression or unacceptable toxicity. Results No treatment related death occurred in this study. Main reported toxicities included: myelosuppression (82.2%), hepatic impairment (42.2%), anorexia (20.0%), nausea (24.4%), vomiting (22.2%), diarrhea (20.0%), febrile (20.0%) and fatigue (24.4%). No complete response was observed. Two patients (2/42) had partial response, twenty-one (21/42) remained stable, and nineteen (19/42) had progressive disease. Median time to tumor progression was 3.0 months (range, 0.5-12.0). Median overall survival was 30.0 months (95% confidence interval: 20.0-40.0) and 1 year survival rate was 81.0%. Conclusion Our study revealed that toxicity of Endostar combined with chemotherapy in the treatment of solid tumors was tolerable with moderate efficacy.

Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors.

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Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors.