Comparison of toxicity profiles of fluorouracil versus oxaliplatin regimens in a large population-based cohort of elderly patients with colorectal cancer.

BACKGROUND: Population-based studies of adverse events are scarce. Our objective was to evaluate chemotherapy-associated adverse events among elderly colorectal cancer (CRC) patients treated in the community. PATIENTS AND METHODS: Data on elderly patients aged ≥65 years diagnosed with CRC at any stage between 2003 and 2005 were obtained from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Database. RESULTS: Of 46 692 patients assessed, 36 137 (77.4%) received no i.v. chemotherapy, 5472 (11.7%) received fluorouracil (5-FU) alone, 2284 (4.9%) received oxaliplatin-containing regimens, 1306 (2.8%) received bevacizumab-containing regimens but without oxaliplatin, and 1493 (3.2%) received other chemotherapy. Symptoms and laboratory test abnormalities were commonly found in elderly, even in those who had not received any i.v. chemotherapy. The addition of i.v. chemotherapy was associated with higher incidences of adverse events. Oxaliplatin-based regimens led to higher incidences in nausea, neutropenia, and neuropathy compared with 5-FU alone. Patients aged ≥70 years (n = 37 601, 80.5%) tended to experience higher rates of certain adverse events, including infection, anemia, delirium, and heart disease than patients aged 65-69 years (n = 9091, 19.5%). CONCLUSIONS: Among community-dwelling elderly with CRC, the addition of i.v. chemotherapy and advanced age were associated with increasing adverse events. Appropriate selection of patients and assessment of social support may be important.

Adenocarcinoma of the lower esophagus with Barrett's esophagus or without Barrett's esophagus: differences in patients' survival after preoperative chemoradiation.

It remains unclear whether the overall survival (OS) of patients with localized esophageal adenocarcinoma (LEA) with Barrett's esophagus (BE) (Barrett's-positive) and those with LEA without BE (Barrett's-negative) following preoperative chemoradiation is different. Based on the published differences in the molecular biology of the two entities, we hypothesized that the two groups will have a different clinical biology (and OS). In this retrospective analysis, all patients with LEA had surgery following preoperative chemoradiation. Apart from age, gender, baseline clinical stage, location, class of cytotoxics, post-therapy stage, and OS, LEAs were divided up into Barrett's-positive and Barrett's-negative groups based on histologic documentation of BE. The Kaplan-Meier and Cox regression analytic methods were used. We analyzed 362 patients with LEA (137 Barrett's-positive and 225 Barrett's-negative). A higher proportion of Barrett's-positive patients had (EUS)T2 cancers (27%) than those with Barrett's-negative cancer (17%). More Barrett's-negative LEAs involved gastroesophageal junction than Barrett's-positive ones (P = 0.001). The OS was significantly shorter for Barrett's-positive patients than that for Barrett's-negative patients (32 months vs. 51 months; P = 0.04). In a multivariate analysis for OS, Barrett's-positive LEA (P = 0.006), old age (P = 0.016), baseline positive nodes (P = 0.005), more than 2 positive (yp)N (P = 0.0001), higher (yp)T (P = 0.003), and the use of a taxane (0.04) were the independent prognosticators. Our data demonstrate that the clinical biology (reflected in OS) is less favorable for patients with Barrett's-positive LEA than for patients with Barrett's-negative LEA. Our intriguing findings need confirmation followed by in-depth molecular study to explain these differences.

Kinetics of simultaneous saccharification and lactic acid fermentation processes.

After pretreatment of corn cob by dilute acid, the lignocellulosic residue was used as raw materials for the simultaneous saccharification and lactic acid fermentation (SSLF). Because of the same optimal temperature and pH requirement as well as the anaerobic condition, the lactic acid fermentation is perfectly compatible with enzymatic hydrolysis of cellulosic materials. In the SSLF processes, the final concentration of lactic acid reached 33.97 g/L with a conversion ratio of 79% based on the consumed cellulose. A mathematical model is suggested to simulate the SSLF process with good agreement.

[Studies on the induction of L-phenylalanine ammonia lyase(PAL) in Rhodotorula glutinis and transformation of phenylalanine from trans-cinnamic acid].

The induction of PAL in Rhodotorula glutinis and transformation of L-phenylalanine from trans-cinnamic acid were studied. The optimum medium for PAL induction was composed of (g/L) 10.0 yeast extract, 10.0 peptone, 5.0 NaCl, 0.5 KH2 PO4, 0.5 phenylalanine 1.0 (NH4)2SO4 and 5.0 glucose, pH 6.0-6.5. The cultivation temperature was 30.0 degrees C. In the process of transformation, the effect of [NH4]+ on initial velocity was in accordance with Michaelis-Menten rate expression in which Km and Vmax were 16.85 mol/L and 5.96 g.L-1.h-1 for ammonia and the optimum pH was 10.0. Substrate activation and inhibition were observed at low and high concentration of cinnamic acid. The yield of phenylalanine from cinnamic acid reached more than 60.0%.

[Saccharification of corn stover by immobilized Trichoderma reesei cells].

The mycelia of Trichoderma reesei Rut C30 were adsorbed and immobilized within the porous polyurethane supporter. It was found that the synthesis of cellulase by the immobilized cells and the enzymatic hydrolysis of corn stover were able to be carried out in a nitrogen source-limiting medium. Under repeated batch processes with 60 g/L corn stover pretreated by 2% NaOH at 85 degrees C, the average cellulase activity (FPA) was 0.70 IU/ml, the concentration and yield of the reducing sugar were 26.41 g/L and 89.11% respectively after shaking culture at 150 r/min, 30 degrees C, pH 4.8 for 108 h. Total of 12 repeated batches were performed in 54 days. The immobilized cells kept the weight around 10 g/L. The fed-batch process was also studied with the same immobilized cells. Total of 120 g/L corn stover was added in different feeding manners. The reducing sugar of 52.8 g/L was produced after 7 days and the saccharification efficiency (89.2%) was almost the same as the batch process. The results indicated that the cellulase production and cellulosic material saccharification in situs by the immobilized Trichoderma reesei cells is an convenient and effective process for conversion and utilization of renewable biomass.

[L-lactic acid fermentation by immobilized Rhizopus oryzae in a three-phase fluidized-bed].

L-lactic acid fermentation in a three-phase fluidized-bed bioreactor was studied by using immobilized Rhizopus oryzae cells with polyurethane particles as supporter. The results indicated that the immobilized cells were stable after used for 8 batches repeatedly. The rate and the yield of lactic acid fermentation with glucose as carbon source were 19.1 g h-1.L (bead)-1 and 82.5%, respectively. With the hydrolyzate of corn cob residue from xylose manufacturer by cellulase hydrolysis, the yield of lactic acid reached 71.9%.

Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

MicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3.

Pancreatic cancer is characterized by extremely poor prognosis because of early recurrence and metastasis, and increasing evidence supports the critical role of microRNA in cancer progression. Here we identified that microRNA-34b functioned as a tumor-suppressing microRNA by targeting oncogenic Smad3 in pancreatic cancer. As a hypovascular tumor with a potential endoplasmic reticulum stress microenvironment, miR-34b was silenced after ER stress inducer thapsigargin (Tg) treatment and negatively regulated by ER stress chaperone glucose regulated protein 78 (GRP78) in pancreatic cancer cells. In human specimens, we found that miR-34b was down-regulated in pancreatic cancer tissues and low level of miR-34b expression was positively correlated with tumor-node-metastasis (TNM) stage, lymph-node metastasis and overall survival. Functional assays showed that over-expression of miR-34b inhibited pancreatic cancer progression in vitro and in vivo. In addition, Smad3 was demonstrated as a direct target of miR-34b and negatively regulated by miR- 34b at mRNA and protein levels. Luciferase assays confirmed that miR-34b could directly bind to the 3'untranslated region of Smad3. An inverse correlation between miR-34b and Smad3 was observed in 64 pancreatic cancer tissues. Our findings indicate that miR-34b acts as a tumor metastasis suppressor through negatively modulating Smad3, which may provide a potential therapeutic strategy for pancreatic cancer.

Enhanced production of spinosad in Saccharopolyspora spinosa by genome shuffling.

Spinosad (spinosyns A and D) is a mixture of secondary metabolites produced by Saccharopolyspora spinosa. It is used in agriculture as a potent insect control agent with exceptional safety to non-target organisms. In this study, we applied genome shuffling of S. spinosa to achieve a rapid improvement of spinosad production. Ten strains with subtle improvements in spinosad production were obtained from the populations generated by the mutation with nitrosoguanidine and ultraviolet irradiation, and then they were subjected for recursive protoplast fusion. After four rounds of genome shuffling, a high yielding strain, designated as S. spinosa 4-7, was successfully isolated. Its production reached 547 mg/L, which was increased by 200.55% and 436.27% in comparison with that of the highest parent strain and the original strain, respectively. The subculture experiments indicated that the high producer of S. spinosa 4-7 was stable. Spinosad fermentation experiments by S. spinosa 4-7 were carried out in a 5-L fermentor, and its production of spinosad reached 428 mg/L after 168 h of fermentation.

[The effects of different glucose feeding modes on hEGF production in an excretory recombinant Escherichia coli K12 system].

The effects of different glucose feeding modes on hEGF expression were evaluated in an excretory recombinant E. coli K12 system. The results showed that, compared with batch cultivation, the plasmid stability and density of plasmid-retaining cells were improved by all three glucose feeding modes (intermittent, pH-stat and constant-rate). It was shown that hEGF yields were improved up to 25.5% and 28.1% by intermittent or pH-stat glucose feeding respectively. Especially, up to 150% improvement of hEGF production was achieved by constant feeding of 200 g/L glucose solution at a rate of 0.11 mL/min. The effects of further combined feeding with other medium components (ampicillin, nitrogen sources, and inorganic salts) and inducer on hEGF yield were also examined in the bench-top fermentor.

Kinetic models of batch and fed-batch culture of single-cell protein with double carbon sources.

Unstructured logistic models were applied to simulate the kinetic process of the SCP batch culture with two species of yeast, in which glucose, xylose, or a mixture of the two were used as carbon sources. A modified logistic growth model was used to describe the fed-batch process of using mixed carbon sources. The model parameters were determined by the simulated model with the experimental data. The simulated curves of the models were in agreement with the experimental data.

Production of teicoplanin by valine analogue-resistant mutant strains of Actinoplanes teichomyceticus.

Teicoplanin is a glycopeptide antibiotic produced by Actinoplanes teichomyceticus. A strain improvement to increase the productivity of the major component, teicoplanin A2-2, was carried out. As the fatty moiety of teicoplanin A2-2 is derived from L-valine, L-valine analogue (valine hydroxamate)-resistant mutants were derived. One of the mutants, 98-1-227, overproduced valine and produced a higher titer of total teicoplanin with higher A2-2 content. In a pilot fermentor (7 m3), the total productivity of teicoplanin was 1,800 units/ml and the A2-2 content was 58%.

[Studies on simultaneous production of chitosanase and chitosan degradation in situ with Trichoderma reesei in convoluted fibrous bed bioreactor].

The cells of Trichoderma reesei were immobilized on a roll of porous polyurethane foam sheet and packed in a bubble column bioreactor for simultaneous production of chitosanase and degradation of chitosan in situ. The average degree of polymerization could be regulated by reaction time. Under the repeated-batch process with 2% soluble chitosan at pH4.8, 28 degrees C, the activity of chitosanase for each batch was above 0.15 IU/mL, the average yield of reducing sugar as D-glucosamine reached 73%. The novel immobilized bioreactor system run stably and effectively in the successive 10 batches lasting 30 days without notable change in the activity and productivity.

Extractive L-lactic acid fermentation with immobilized Rhizopus oryzae in a three-phase fluidized bed.

The Rhizopus oryzae was immobilized by the calcium alginate entrapment method. A three-phase fluidized-bed bioreactor was designed to perform the immobilized-cell L-lactic acid fermentation. A solvent extraction column was coupled with the bioreactor to remove L-lactic acid from the fermentation broth. The TRPO was selected as solvent and sulfonated kerosene as diluent. The results indicated that the pH value in the broth was regulated above pH 3.5 and the fermentation rate was as high as 11 g L-lactic acid per hour per liter of beads. A mathematical model was proposed to describe the concentration of L-lactic acid in the extractive fermentation.