Search Results - (Author, Cooperation:W. K. Hong)

2014-10-11

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Adenocarcinoma/*genetics/pathology ; DNA Mutational Analysis ; Exome/genetics ; Genes, Neoplasm ; *Genetic Heterogeneity ; Humans ; Lung Neoplasms/*genetics/pathology ; Mutation ; Neoplasm Recurrence, Local/*genetics/pathology

1434-0879

Cytoreductive surgery ; Chemotherapy ; Renal adenocarcinoma ; Rats

Springer Online Journal Archives 1860-2000

Medicine

Summary The potential ability of cytoreductive surgery to increase the effectiveness of chemotherapy (vindesine) was tested utilizing male Wistar Lewis rats transplanted simulataneously with intraperitoneal and flank implants of a spontaneously arising renal adenocarcinoma. Cytoreduction was accomplished in some animals by removing the flank tumor 5–7 weeks following implantation; all animals received vindesine (IP injection of 0.5 mg/kg on two successive weeks). While vindesine reduced tumor growth, in no case did the addition of cytoreductive surgery enhance the effect of chemotherapy. The addition of cytoreductive surgery to marginally effective chemotherapy was found to be ineffective or even detrimental.

Electronic Resource

1432-0614

Springer Online Journal Archives 1860-2000

Biology

Process Engineering, Biotechnology, Nutrition Technology

Abstract  In order to direct the persistent expression of recombinant human serum albumin (HSA) from the GAL10 promoter in the yeast Saccharomyces cerevisiae, we carried out periodic feeding of galactose during shake-flask cultures. Unexpectedly, the recombinant protein secreted was observed to undergo rapid degradation, which was apparently accelerated by carbon-source feeding. The extracellular degradation of HSA occurred even in the strain deficient in the major vacuolar proteases PrA and PrB, and in the strain lacking the acidic protease Yap3p (involved in the generation of HSA-truncated fragments). Interestingly, the degradation correlated closely with the acidification of extracellular pH and thus was significantly overcome either by buffering the culture medium above pH 5.0 or by adding amino acid-rich supplements to the culture medium, which could prevent the acidification of medium pH during cultivation. Addition of arginine or ammonium salt also substantially minimized the degradation of HSA, even without buffering. The extracellular degradation activity was not detected in the cell-free culture supernatant but was found to be associated with intact cells. The results of the present study strongly suggest that the HSA secreted in S. cerevisiae is highly susceptible to the pH-dependent proteolysis mediated by cell-bound protease(s) whose activity and expression are greatly affected by the composition of the medium.

Electronic Resource

1569-8041

phase I trial ; retinoid ; solid tumors ; vitamin E

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background: Retinoids are under intensive study for the treatment andprevention of cancer. Substantial dose-related toxicities of retinoids are amajor obstacle to this work. In a recent retrospective analysis of combined13-cis-retinoic acid (13cRA) and alpha-tocopherol (AT) in myelodysplasia,13cRA toxicity was reduced significantly and 13cRA activity was enhanced.These results suggested the need for prospective testing of this newcombination. This trial tested the hypotheses that AT can reduce toxicity ofhigh-dose 13cRA and does not interfere with 13cRA absorption/activity asreflected by reduced 13cRA serum levels. Patients and methods: This was a phase I trial design in whichpatients received fixed-dose 13cRA (100 mg/m2/d) plusescalating-dose AT (beginning at 800 IU/d, increased 400 IU/d each month until2000 IU/d). We collected toxicity data every four weeks from self-reportforms, clinical examinations and laboratory studies. AT effects on 13cRAtoxicity were determined by comparing maximum toxicity at lowest AT dose withthat at highest AT dose. We also measured serum levels of both agents everyfour weeks. Results: Of the 45 patients registered, 36 had cancer (active orprior history), 9 had premalignant lesions. Thirty-nine patients could beevaluated for initial-course toxicity; 31 for final-course toxicity. Mediantime on treatment (all patients) was four months (range, 1–9 months);a total of 223 month-long courses of treatment were given. Eighteen percentof patients (7/39) developed grade 3 or 4 toxicity in the initial course. Therates of increase and decrease in 13cRA toxicity associated with increasingAT doses were similar: 36% decreased (11/31), 32% increased(10/31) (P = 0.84). AT did not reduce 13cRA serum levels. After initialincreases of mean AT plasma levels (17.9 µg/ml at baseline to 45.4µg/ml after first four-week course), subsequent AT plasma increases(〈2-fold) did not keep pace with increased AT doses (2–3-fold). Nomajor activity occurred in the 21 patients with active refractory cancer. Thecomplete response rate in patients with premalignant head-and-neck or lunglesions was 77.8% (7/9), which included two patients previouslyrefractory to 13cRA alone. Conclusion: Although escalating doses of AT did not reduce 13cRAtoxicity, the rate of initial-course (including 800 IU/d of AT) high-gradetoxicity was substantially lower than that typical of high-dose 13cRA-aloneand similar to that typical of low-dose 13cRA-alone. Indeed, a trial of13cRA-alone followed by 13cRA plus AT may have detected a significant toxicitydifference. We did not design such a trial out of ethical concern for knownside effects of high-dose 13cRA. The increase in AT serum levels was notproportional with increasing doses of AT, which may explain the lack of adose-response effect of AT on 13cRA toxicity. Previous trials have establishedthat 13cRA has an approximate 10% complete response rate in oralpremalignancy. Our small trial's 77.8% complete response rate inpremalignant lesions suggests that AT may enhance 13cRA clinical activity.Future trials of 13cRA plus AT are needed to define this combinationåstoxicity profile, clinical activity and pharmacokinetics.

Electronic Resource

1573-0646

tallysomycin S10b ; head and neck cancer

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary Twenty patients with advanced head and neck tumors were entered in a phase II trial of tallysomycin S10b given intravenously at weekly doses of 2.5 mg/m2. All patients had received prior chemotherapy ± radiotherapy. Sixteen patients were evaluable for response. Two had stable disease for 15 and 22 weeks respectively. None exhibited tumor shrinkage. Non-hematologic toxicities primarily consisted of gastrointestinal intolerance. Mild fever was noted in about half of the patients and increase in serum creatinine was observed in four. Other side effects consisted of decrease in pulmonary diffusion capacity and skin changes. In conclusion, tallysomycin S10b has no activity in previously treated head and neck cancer patients and has a toxicity spectrum similar to that of bleomycin.

Electronic Resource

0178-515X

Springer Online Journal Archives 1860-2000

Process Engineering, Biotechnology, Nutrition Technology

Abstract Production of D-β-hydroxyisobutyric acid (D-HIBA) from methacrylic acid (MA) was investigated using Candida rugosa IFO 0750 and its mutant. Cell growth decreased as the MA concentration increased and was inhibited at D-HIBA concentrations higher than 30 g/l. Optimal MA concentration for D-HIBA production was in the range of 10–20 g/l. It was also noted that cell growth and D-HIBA production were inhibited by higher concen-trations of Na+, K+, and NH4 +, which were required for pH control during cultivation. With a suitably designed feeding mode of MA, the parent strain produced 65 g/l of D-HIBA after 120 h of fed-batch cultivation, but molar conversion yield of D-HIBA was less than 40%. The mutant, unable to assimilate propionic acid, produced as high as 70 g/l of D-HIBA in the same culture period with a molar conversion yield of more than 70%.

Electronic Resource