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Phase II trial of combined irinotecan and oxaliplatin given every 3 weeks to patients with metastatic colorectal cancer
Hoff, Paulo M.; Wolff, Robert A.; Xiong, Henry ...
Cancer,
15 May 2006, Volume:
106, Issue:
10
Journal Article
BACKGROUND
Both irinotecan and oxaliplatin are active agents in the treatment of patients with metastatic colorectal cancer, and there is a strong preclinical rationale for combining these 2 agents. ...
Therefore, a Phase II trial was designed and conducted to determine the efficacy and tolerability of combined irinotecan and oxaliplatin given every 3 weeks to patients with metastatic colorectal cancer.
METHODS
Patients with previously untreated metastatic colorectal cancer received irinotecan at a dose of 175 mg/m2 and oxaliplatin at a dose of 130 mg/m2, both given intravenously every 3 weeks. Objective responses were evaluated every 2 courses and were confirmed at least 4 weeks after the initial determination.
RESULTS
Fifty‐five patients were enrolled and treated in the current trial. Of the 53 patients whose responses were evaluable, 18 (34%) achieved a partial response, 27 (51%) had stable disease, and 8 (15%) developed disease progression as their best response to the treatment. The intent‐to‐treat median survival for all patients was 16.4 months and the time to progression was 4.8 months. All 55 patients were available for toxicity analysis (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria). The most common Grade 3‐4 toxic effect was neutropenia, which was reported to occur in 22 patients (40%).
CONCLUSIONS
The combination of irinotecan and oxaliplatin appears to be safe and active when used to treat patients with metastatic colorectal cancer. Treatment results with this regimen were similar to those reported for other combined frontline chemotherapy regimens for colorectal cancer. When this particular regimen wa used, neutropenia was found to be the predominant toxicity. Cancer 2006. © 2006 American Cancer Society.
The combination of irinotecan and oxaliplatin appears to be safe and active when used to treat patients with metastatic colorectal cancer. Treatment results with this regimen were found to be similar to those reported for other combined frontline chemotherapy regimens for colorectal cancer. When this particular regimen was used, neutropenia was the predominant toxicity.
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93.
Pulmonary hypertension alters soluble guanylate cyclase activity and expression in pulmonary arteries isolated from fetal lambs
Tzao, Ching; Nickerson, Peter A.; Russell, James A. ...
Pediatric pulmonology,
February 2001, Volume:
31, Issue:
2
Journal Article
The nitric oxide (NO)‐guanosine 3′,5′‐cyclic monophosphate (cGMP) signaling pathway plays an important role in the pulmonary vascular transition at birth. We studied pulmonary arteries and veins ...
isolated from normal late‐gestation fetal lambs and from fetal lambs with persistent pulmonary hypertension (PPHN) following prenatal ligation of the ductus arteriosus. We additionally used double immunolabeling and immunoblot analysis to determine relative vascular contents of endothelial nitric oxide synthase (NOS‐III) and soluble guanylate cyclase (sGC).
Cyclic GMP content and sGC activity were significantly lower in arteries from hypertensive lambs than controls. A rank order for contents of both soluble guanylate cyclase and NOS‐III was observed by both immunolabeling and immunoblotting: Control vein = Hypertensive vein > Control artery > Hypertensive artery.
Our data demonstrate that the relative expression of sGC correlates well with the relative expression of NOS‐III, and indicate the potential importance of soluble guanylate cyclase in the regulation of the perinatal pulmonary circulation. These data may help us understand vascular mechanisms producing PPHN, as well as patterns of response to exogenous NO. Pediatr Pulmonol. 2001; 31:97–105. © 2001 Wiley‐Liss, Inc.
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Respiratory system mechanics in guinea pigs after acute hemorrhage: role of adrenergic stimulation
Martins, M A; Zin, W A; Younes, R N ...
Critical care medicine
18, Issue:
5
Journal Article
We evaluated the effects of acute blood loss on the respiratory mechanics of guinea pigs. We measured respiratory system elastance (Ers) and resistance (Rrsmax) using the end-inflation occlusion ...
method. Rrsmax was partitioned into its homogeneous component (Rrsmin) and that due to the unevenness within the respiratory system (Rrsu). Respiratory mechanics were studied both before and immediately after bleeding in eight animals. Another eight guinea pigs had received propranolol previously and were also submitted to hemorrhage. Propranolol-treated animals showed higher control values of Rrsmax (p less than .02) and Rrsmin (p less than .0001). Animals not treated with propranolol exhibited a decrease (p less than 0.001) in Rrsmax after hemorrhagic hypovolemia (from 0.375 +/- 0.051 to 0.323 +/- 0.042 cm H2O/ml.sec), due to a decrease (p less than 0.005) in Rrsmin (from 0.140 +/- 0.031 to 0.094 +/- 0.032 cm H2O/ml.sec), whereas Ers and Rrsu did not change. Propranolol-treated animals showed an increase (p less than .001) in Rrsmax (from 0.512 +/- 0.133 to 0.664 +/- 0.144 cm H2O/ml.sec), Rrsu (p less than 0.01) from 0.252 +/- 0.09 to 0.345 +/- 0.139 cm H2O/ml.sec, and Ers (p less than 0.001) (from 4.565 +/- 0.933 to 5.402 +/- 1.24 cm H2O/ml) after bleeding. The results indicate that the immediate effects of acute bleeding on respiratory mechanics are significantly influenced by catecholamines.
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