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At least 883 records · Page 49Linked to original sources
PubMed2003

Recombinant human angiostatin by twice-daily subcutaneous injection in advanced cancer: a pharmacokinetic and long-term safety study.

PURPOSE: A clinical study was performed to evaluate the pharmacokinetics (PK) and toxicity of three dose levels of the angiogenesis inhibitor recombinant human (rh) angiostatin when administered twice daily by s.c. injection. EXPERIMENTAL DESIGN: Eligible patients had cancer not amenable to standard treatments. Three groups of 8 patients received 7.5, 15, or 30 mg/m(2)/day divided in two s.c. injections for 28 consecutive days followed by a 7-day washout period. PK assessment was done at days 1 and 28. Thereafter, in absence of toxicity or a 100% increase in tumor size, treatment was continued without interruption. RESULTS: Median age was 53 years (range, 43-75), male:female ratio 10:14, Eastern Cooperative Oncology Group performance 0-1. At the range of doses evaluated, serum PK of all 24 of the patients showed linear relation between dose and area under the curve (0- infinity) and C(max) (reached after 2 h). Thirteen of 24 patients developed erythema at injection sites (11 patients, CTC grade 1; 2 patients, CTC grade 2) without pain or itching, spontaneously resolving within 2-3 weeks of treatment. Two patients went off study after developing hemorrhage in brain metastases, and 2 patients developed deep venous thrombosis. No other relevant treatment-related toxicities were seen, even during prolonged treatment. A panel of coagulation parameters was not influenced by rhAngiostatin treatment. Long-term (>6 months) stable disease (<25% growth of measurable uni- or bidimensional tumor size) was observed in 6 of 24 patients. Five patients received rhAngiostatin treatment for >1 year (overall median time on treatment 99 days). CONCLUSIONS: Long-term twice-daily s.c. treatment with rhAngiostatin is well tolerated and feasible at the selected doses, and merits additional evaluation. Systemic exposure to rhAngiostatin is within the range of drug exposure that has biological activity in preclinical models.

Adult↗
PubMed2005

Subcutaneous injections of a TNF-alpha antagonistic peptide inhibit both inflammation and bone resorption in collagen-induced murine arthritis.

The cyclic peptide WP9QY (YCWSQYLCY), which was designed to mimic the most critical tumor necrosis factor (TNF) alpha recognition loop on type1 TNF receptor, antagonizes the effects of TNFalpha. In this study, we investigated the effects of WP9QY peptide on collagen-induced arthritis (CIA) mice to evaluate its effects on inflammatory bone destruction. DBA/1J mice were injected intradermally at the base of the tail with bovine type II collagen, emulsified in complete Freund's adjuvant on day 0 and 21. The three sets of WP9QY peptide injections (24 mg/kg x 8 times per day) were performed before the onset of paw swelling. Mice were sacrificed at day 38 and thereafter, the arthritis scores as well as radiographical and histological outcomes were assessed. WP9QY peptide inhibited CIA-induced increase in the arthritis score. Furthermore, histomorphometric analysis of the tibial epiphysis region revealed that WP9QY peptide inhibited the increase of synovial pannus infiltration and the decrease of bone volume, which were induced by the CIA. The WP9QY treatment prevented the inflammation as well as bone destruction of the joints in the CIA mice, suggesting that the administration of WP9QY peptide might be useful for developing a drug to prevent inflammatory bone destruction.

Animals↗
PubMed1989

Influence of esophagojejunostomy on the induction of adenocarcinoma of the distal esophagus in Sprague-Dawley rats by subcutaneous injection of 2,6-dimethylnitrosomorpholine.

To study the influence of reflux esophagitis on the carcinogenic response of 2,6-dimethylnitrosomorpholine (2,6-DMNM), an experiment was designed, composed of 6 groups of 8-week-old Sprague-Dawley rats, each consisting of 20 males and 20 females. Group 1 served as untreated controls. All animals of groups 2, 4, and 6 underwent an esophagojejunostomy with gastric preservation to produce a chronic reflux esophagitis. 2,6-DMNM was injected s.c. once weekly for life at doses of 1/100 and 1/10 of the 50% lethal dose to groups 3 and 4 and groups 5 and 6, respectively. Carcinogen exposure began in groups 4 and 6 15 days after the esophagojejunostomy. Squamous cell carcinomas were observed in the esophagus of 36 animals, mainly in those receiving the higher dose. Exophytic squamous cell carcinomas, a variety rarely seen in humans, were mostly seen in the groups receiving 2,6-DMNM alone, whereas endophytic squamous cell carcinomas, the variety most frequently seen in humans, mainly developed in the groups receiving the combined treatment. In addition adenocarcinomas with abundant mucin production were found in the distal esophagus of 23 animals. They were found exclusively in animals of groups 4 and 6 which underwent esophagojejunostomy plus 2,6-DMNM exposure. No adenocarcinomas were encountered in groups without experimental reflux esophagitis. These findings may contribute to further understanding of the association between reflux esophagitis and the various histological types of esophageal carcinoma in humans.

Adenocarcinoma↗