ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.</p><p><b>METHODS</b>Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.</p><p><b>RESULTS</b>Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.</p><p><b>CONCLUSIONS</b>Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Adenocarcinoma , Drug Therapy , Pathology , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carcinoma, Squamous Cell , Drug Therapy , Pathology , Diarrhea , Disease-Free Survival , Drug Combinations , Fluorouracil , Follow-Up Studies , Leukopenia , Neoplasm Staging , Oxonic Acid , Paclitaxel , Prospective Studies , Remission Induction , Stomach Neoplasms , Drug Therapy , Pathology , Survival Rate , TegafurABSTRACT
<p><b>OBJECTIVE</b>To investigate the changes of pulmonary tissue area density and their mechanisms in rats with hypoxic pulmonary hypertension (HPH).</p><p><b>METHODS</b>54 Wistar rats were divided into hypoxia 10 d (n = 12), 20 d (n = 12), 30 d (n = 12) groups and control group (n = 18). The rats in hypoxia groups were exposed to a simulated hypoxia environment at a height of 5 km above sea level to establish HPH models. The changes in pulmonary tissue area density and pathological morphology were determined by image analysis, optical microscope, electron microscope and histochemistry.</p><p><b>RESULTS</b>After hypoxia, the pulmonary tissue area density markedly increased on 10 d (27.08% +/- 1.29%, P < 0.05), especially on 20 d (31.33% +/- 0.27%) and 30 d (31.10% +/- 1.95%) while that in control group was 22.78% +/- 1.17% (P < 0.01). The area density on 20 d was higher than that on 10 d (P < 0.05) but there wasn't significantly different between 10 d and 30 d (P = 0.057) after hypoxia. Pathological examination showed: edema and collapse of pulmonary tissue, swelling and degeneration of type II alveolus epithelial cells (PII); congestion, accumulation of polymorphonuclear neutrophils and platelets in capillaries; swelling and degeneration of endothelial cells, thickening of basement membranes.</p><p><b>CONCLUSIONS</b>Hypoxia can induce increase in pulmonary tissue area density and decrease in aerial exchange area in alveoli. These changes may be related to the pulmonary collapse caused by the damage of PII and pulmonary surfactant system, structural remodeling of small pulmonary arteries, increase in blood cells and protein granules in alveolar cavity.</p>
Subject(s)
Animals , Male , Rats , Hypertension, Pulmonary , Pathology , Hypoxia , Lung , Pathology , Microscopy, Electron , Random Allocation , Rats, WistarABSTRACT
Objective To explore the effects of hypoxia on the syntheses and secretion of adrenomedullin (AM), calcitonin gene related peptide (CGRP) and c-type natriuretic peptide (CNP) and the relationship between these peptides. Methods Rat models were established with hypoxia for 10, 20 and 30 d respectively and rats under normal altitude were served as control. Pulmonary artery pressure and the maximum increasing speed of right ventricle (RVdp/dtmax) were measured in every group. The dynamic changes of AM, CGRP and CNP concentrations in plasma were studied with radioimmunoassay. Results During hypoxia, pulmonary artery pressure and RVdp/dtmax were enhanced. Plasma AM and CNP concentrations were increased while CGRP was decreased significantly. The plasma level of AM had positive correlation with that of CNP, but negatively correlated with that of CGRP. Conclusion Results indicate that hypoxia may cause pulmonary artery pressure change and right ventricle has compensatory reaction to hypoxic pulmonary hypertension. Dynamic changes of plasma AM, CGRP and CNP concentrations can be regarded as indexes for condition of illness.
ABSTRACT
Objective To explore the effects of hypoxia on the syntheses and secretion of adrenomedullin (AM), calcitonin gene related peptide (CGRP) and c-type natriuretic peptide (CNP) and the relationship between these peptides. Methods Rat models were established with hypoxia for 10, 20 and 30 d respectively and rats under normal altitude were served as control. Pulmonary artery pressure and the maximum increasing speed of right ventricle (RVdp/dtmax) were measured in every group. The dynamic changes of AM, CGRP and CNP concentrations in plasma were studied with radioimmunoassay. Results During hypoxia, pulmonary artery pressure and RVdp/dtmax were enhanced. Plasma AM and CNP concentrations were increased while CGRP was decreased significantly. The plasma level of AM had positive correlation with that of CNP, but negatively correlated with that of CGRP. Conclusion Results indicate that hypoxia may cause pulmonary artery pressure change and right ventricle has compensatory reaction to hypoxic pulmonary hypertension. Dynamic changes of plasma AM, CGRP and CNP concentrations can be regarded as indexes for condition of illness.