Early tumor shrinkage and depth of response in patients with advanced gastric cancer: a retrospective analysis of a randomized phase III study of first-line S-1 plus oxaliplatin vs. S-1 plus cisplatin.

BACKGROUND: We investigated early tumor shrinkage (ETS) and depth of response (DpR) using data from the G-SOX study comparing S-1 plus oxaliplatin with S-1 plus cisplatin as the first-line treatment for advanced gastric cancer (AGC). METHODS: ETS was determined as % decrease in the sum of the longest diameters of the target lesions at the first evaluation of week 6 compared to baseline. DpR was the maximum % shrinkage during the study treatment. The impact of ETS (cutoff value 20%) and DpR (continuous value) on progression-free survival (PFS) and overall survival (OS) were assessed by the log-rank test and Cox regression analysis including prognostic factors obtained in the G-SOX study; ECOG performance status, baseline sum of tumor diameters, disease status (recurrent/unresectable), and histology (diffuse/intestinal). RESULTS: Among 685 patients enrolled in the G-SOX study, 632 patients who had the first tumor evaluation were analyzed. Patients with ETS ≥ 20% had longer PFS (median 4.5 vs. 2.8 months, p < 0.0001) and OS (median 14.8 vs. 10.5 months, p < 0.0001) than those with ETS < 20%. Adjusted hazard ratios of ETS < 20 vs. ≥ 20% were 0.606 (95% confidence interval (CI) 0.506-0.725) for PFS and 0.589 (95% CI 0.492-0.704) for OS. DpR was also significantly associated with PFS and OS (both p < 0.0001). These results were similar between the SOX and CS groups. CONCLUSIONS: In AGC patients receiving the first-line therapy, ETS and DpR might be predictors for PFS and OS.

Biosynthesis of pectic galactan by membrane-bound galactosyltransferase from soybean ( Glycine max Merr) seedlings.

We investigated the properties of a galactosyltransferase (GalT) that is involved in the synthesis of beta-(1-->4)-galactan side chains of pectins. A membrane preparation of etiolated 6-day-old soybean ( Glycine max Merr.) hypocotyls transferred [(14)C]Gal from UDP-[(14)C]Gal into intact and partially hydrolyzed lupin beta-(1-->4)-galactans of various chain lengths as exogenous acceptors, while activity to endogenous acceptors was negligible. Maximal activity occurred at pH 6.5 and 20-25 degrees C in the presence of 25 mM Mn(2+) and 0.75% Triton X-100. The transfer reaction onto the unmodified commercial pectic galactan ( M(r)>150000) from lupin we used was very low but increased when the M(r) of the galactan was reduced by partial acid hydrolysis. Among the partially hydrolyzed galactans, high- M(r) (average M(r) 60000) beta-(1-->4)-galactan was a more efficient acceptor [specific activity 2000-3000 pmol min(-1) (mg protein)(-1)] than low- M(r) (average M(r) 10000 and 5000) polymers. Digestion of the radiolabeled product from high- M(r) galactan with endo-beta-(1-->4)-galactanase released mainly radioactive beta-(1-->4)-galactobiose and Gal, indicating that the transfer of [(14)C]Gal occurred through beta-(1-->4)-linkages. HPLC analysis showed that the enzyme also catalyzes incorporation of Gal into pyridylaminated (PA) beta-(1-->4)-galactooligomers with degree of polymerization at least 5. Gal(7)-PA chains were elongated by attachment of one, two, or three Gal residues leading to the formation of Gal(8-10)-PA.