Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study.

BACKGROUND: Concomitant chemoradiotherapy followed by total mesorectal excision is standard treatment for locally advanced rectal cancer. This approach, however, focuses on local disease control and delays systemic treatment. Induction chemotherapy has the advantage of earlier administration of systemic therapy and may improve distant control. The objective of the current study was to assess the efficacy and toxicity of adding bevacizumab to induction chemotherapy followed by preoperative bevacizumab-based chemoradiotherapy in patients with locally advanced rectal cancer. PATIENTS AND METHODS: Eligible patients had high-risk rectal adenocarcinoma defined by magnetic resonance imaging criteria. Treatment consisted of four 21-day cycles of bevacizumab (7.5 mg/kg) and XELOX (capecitabine plus oxaliplatin), followed by concomitant radiotherapy (50.4 Gy) plus bevacizumab (5 mg/kg every 2 weeks) and capecitabine (825 mg/m2 twice daily on days 1-15). Surgery was scheduled for 6-8 weeks after chemoradiotherapy. The primary endpoint was pathologic complete response (pCR). RESULTS: Between July 2007 and July 2008, 47 patients were recruited. Among 45 patients who underwent surgery, pCR was achieved in 16 patients (36%; 95% confidence interval: 22.29%-51.27%), and an additional 17 patients (38%) had Dworak tumor regression grade 3. R0 resection was performed in 44 patients (98%). Most grade 3/4 adverse events occurred during the induction phase and included diarrhea (11%), asthenia (4%), neutropenia (6%), and thrombocytopenia (4%). Eleven patients (24%) required surgical reintervention. CONCLUSIONS: Addition of bevacizumab to induction chemotherapy and chemoradiotherapy is feasible, with impressive activity and manageable toxicity. However, caution is recommended regarding surgical complications.

Cetuximab given every 2 weeks plus irinotecan is an active and safe option for previously treated patients with metastatic colorectal cancer.

BACKGROUND: We gathered data from multiple institutions on the cetuximab regimen of patients with metastatic colorectal cancer. METHODS: 126 patients from 19 centers were included from July 2006 to July 2007 in this prospective non-controlled study. Irinotecan-refractory metastatic colorectal cancer patients with Karnofsky >or=70 received cetuximab 500 mg/m(2) every 2 weeks (q2w) in combination with irinotecan 180 mg/m(2) q2w until disease progression or unacceptable toxicity. The primary endpoint was the progression-free rate at 12 weeks. RESULTS: Median age was 65 years; 65.9% male; colon/rectum 64.3/34.1%; Karnofsky status or=90% in 45.3/54.7% of the patients. The progression-free rate was 42.7 (95% CI 32.8-52.6) and 22.4% (95% CI 14.2-30.7) at 12 and 24 weeks, respectively. The main grade 3 or 4 toxicities were: diarrhea 13.5% and acne-like rash 10.3%. No grade 3 or 4 infusional or allergic reactions were reported. CONCLUSIONS: The progression-free rates confirm that cetuximab q2w in combination with irinotecan is an option, and is as active and safe as the standard weekly regimen.

Cell wall compounds of red grapes skins and their grape marcs from three different winemaking techniques.

Different winemaking practices are aimed at increasing cell wall degradation to facilitate extraction of valuables molecules into the wine. However, little attention has been paid to the composition of marcs from different cultivars according to the influence of the winemaking procedures. We provide information on skin cell walls from Cabernet Sauvignon, Syrah and Monastrell grapes and examine how different winemaking practices (addition of enzymatic preparation and ß-galactosidase separately and dry ice addition) may affect the composition of marc skin cell wall material (CWM). The efficiency of CWM isolation from the grape skin and also its composition is influenced by the cultivar. A similar cultivar influence has been detected on CWM from the marc, being the differences also due to the enological technique. Our results help to increase our knowledge on the degradation of cell walls during vinification, while providing a valuable guideline to upgrade the value of these by-products.

The composition of cell walls from grape marcs is affected by grape origin and enological technique.

The grape marc obtained after vinification could be a source of high value compounds and the different winemaking techniques could influence such compounds. The composition of skin cell walls from Monastrell grapes grown in three different locations near Murcia (S.E. Spain) has been studied. The grapes were winemaked with three different techniques (cold pre-fermentative maceration, ß-galactosidase enzyme addition and enzymatic preparation addition) and the marc skin cell walls were studied to determine their composition. The results suggest that terroir influenced the percentage of grape skin, the amount of cell wall material isolated from the grape skin, the carbohydrate composition of the cell wall material, and the lignin and protein content of the cell wall material from grape skin. A similar trend has been found within the influence of terroir on cell wall material isolated from the skin separated from the marc, being the differences also due to the enological technique.

Oligosaccharides of Cabernet Sauvignon, Syrah and Monastrell red wines.

Wine oligosaccharides were recently characterized and their concentrations, their composition and their roles on different wines remain to be determined. The concentration and composition of oligosaccharides in Cabernet Sauvignon, Syrah and Monastrell wines was studied. Oligosaccharide fractions were isolated by high resolution size-exclusion chromatography. The neutral and acidic sugar composition was determined by gas chromatography. The MS spectra of the oligosaccharides were performed on an AccuTOF mass spectrometer. Molar-mass distributions were determined by coupling size exclusion chromatography with a multi-angle light scattering device (MALLS) and a differential refractive index detector. Results showed significant differences in the oligosaccharidic fraction from Cabernet Sauvignon, Syrah and Monastrell wines. This study shows the influence that the grape variety seems have on the quantity, composition and structure of oligosaccharides in the finished wine. To our knowledge, this is the first report to research the oligosaccharides composition of Cabernet Sauvignon, Syrah and Monastrell wines.

Effect of enzyme additions on the oligosaccharide composition of Monastrell red wines from four different wine-growing origins in Spain.

The release of oligosaccharides during winemaking depends on the grape skin cell wall degradation, which can be facilitated by the use of enzymes. Oligosaccharide quantities and composition in wine could be influenced by the "terroir" effect. Monastrell wine was elaborated from grapes from four different "terroirs" (Cañada Judío, Albatana, Chaparral-Bullas and Montealegre). Monastrell wines were also treated with ß-galactosidase enzyme addition and commercial enzyme addition. The results showed significant differences in the Monastrell wine oligosaccharide fractions, according to the geographical origin of grapes. A higher quantity of oligosaccharides was found for three out of four terroirs studied when commercial enzymes were added. The use of commercial enzyme modified the Arabinose/Galactose and the Rhamnose/Galacturonic acid ratios in Cañada Judío and Albatana terroirs wines, and it modified the (Arabinose+Galactose)/Rhamnose ratio in Cañada Judío, Albatana and Chaparral-Bullas terroirs wines. Therefore, the "terroir" impacts the effect of commercial enzyme treatment on wine oligosaccharide composition.

Polysaccharide composition of Monastrell red wines from four different Spanish terroirs: effect of wine-making techniques.

Monastrell wines made from grapes grown in four different Spanish "terroirs" (Cañada Judío, Albatana, Bullas, and Montealegre) were studied. Different wine-making techniques were also used, including different refrigeration techniques (prefermentative cold maceration and dry ice addition) and the addition of two different enzymes (ß-galactosidase and commercial pectinase enzyme). The results pointed to significant differences in the Monastrell wine polysaccharide fractions according to the geographical origin of the grapes. The Rhamnogalacturonan II (RG-II) concentration was 2-fold higher in the Montealegre terroir than in the Bullas terroir. The use of enzymes also modified the polysaccharide content of the wines. RG-II levels were higher in the wines from three terroirs when commercial enzymes were added. The arabinose/galactose ratio of one of the wines was modified by the use of enzymes during wine-making, and some prefermentative cold maceration samples showed high values for several polysaccharides. This study shows the great importance of the "terroir effect" in the polysaccharide composition of wines.

Evaluating the Polyphenol Profile in Three Segregating Grape (Vitis vinifera L.) Populations.

This paper explores the characteristics of the anthocyanin and flavonol composition and content in grapes from plants resulting from intraspecific crosses of Vitis vinifera varieties Monastrell × Cabernet Sauvignon, Monastrell × Syrah, and Monastrell × Barbera, in order to acquire information for future breeding programs. The anthocyanin and flavonol compositions of twenty-seven hybrids bearing red grapes and 15 hybrids bearing white grapes from Monastrell × Syrah, 32 red and 6 white from Monastrell × Cabernet Sauvignon, and 13 red from Monastrell × Barbera have been studied. Among the intraspecific crosses, plants with grapes presenting very high concentrations of anthocyanins and flavonols were found, indicating a transgressive segregation for this character, and this could lead to highly colored wines with an increased benefits for human health. As regards the qualitative composition of anthocyanins and flavonols, the hydroxylation pattern of the hybrids that also may influence wine color hue and stability presented intermediate values to those of the parentals, indicating that values higher than that showed by the best parental in this respect will be difficult to obtain. The results presented here can be helpful to acquire information for future breeding efforts, aimed at improving fruit quality through the effects of flavonoids.

Increasing the phenolic compound content of grapes by preharvest application of abcisic acid and a combination of methyl jasmonate and benzothiadiazole.

Benzothiadiazole (BTH) and methyl jasmonate (MeJ) have been described as exogenous elicitors of some plant defense compounds, polyphenols among them. Given that they activate different arrays of biochemical reactions to induce resistance, the objective of this study was to determine whether the joint application of BTH and MeJ to grape clusters affects the level of the main flavonoid compounds in grapes and in the resulting wines. The results are compared with those obtained when abscisic acid (ABA), a plant growth regulator involved in several physiological processes, was sprayed in the same vineyard. The results obtained indicated that, although the application of ABA increased the content of skin anthocyanins and tannins, these positive effects were not reflected in the wines made from these grapes. BTH+MeJ-treated grapes also presented higher anthocyanin and flavonol contents, and in this case, their wines presented better chromatic characteristics that the wine made from control grapes.

Improving grape phenolic content and wine chromatic characteristics through the use of two different elicitors: methyl jasmonate versus benzothiadiazole.

Benzothiadiazole (BTH) and methyl jasmonate (MeJ) have been described as exogenous elicitors of some plant defense compounds, polyphenols among them. The objective of this study was to determine whether the application of BTH or MeJ to grape clusters at the beginning of the ripening process had any effect on the accumulation of the main flavonoid compounds in grapes (anthocyanins, flavonols, and flavanols) and the technological significance of these treatments in the resulting wines. The results obtained after a 2 year experiment indicated that both treatments increased the anthocyanin, flavonol, and proanthocyanidin content of grapes. The wines obtained from the treated grapes showed higher color intensity and total phenolic content than the wines made from control grapes. The exogenous application of these elicitors, as a complement to fungicide treatments, could be an interesting strategy for vine protection, increasing, at the same time, the phenolic content of the grapes and the resulting wines.

Effect of micro-oxygenation on color and anthocyanin-related compounds of wines with different phenolic contents.

Several factors may affect the results obtained when micro-oxygenation is applied to red wines, the most important being the moment of application, the doses of oxygen, and the wine phenolic characteristics. In this study, three red wines, made from Vitis vinifera var. Monastrell (2005 vintage) and with different phenolic characteristics, were micro-oxygenated to determine as to how this technique affected the formation of new pigments in the wines and their chromatic characteristics. The results indicated that the different wines were differently affected by micro-oxygenation. In general, the micro-oxygenated wines had a higher percentage of new anthocyanin-derived pigments, being that this formation is more favored in the wines with the highest total phenol content. These compounds, in turn, significantly increased the wine color intensity. The wine with the lowest phenolic content was less influenced by micro-oxygenation, and the observed evolution in the degree of polymerization of tannins suggested that it might have suffered overoxygenation.