Contributions of Intermolecular Interactions between Constitutive Arabinoxylans to the Flaxseeds Mucilage Properties

International audienceThe main fraction (about 75%) of the mucilage extracted from seeds of Linum usitatissimum which consists of arabino-xylans (AX) has been studied in dilute and semidilute regimes by SEC/MALLS analysis and rheology, respectively. It has been found that AX contains 3 populations of about 5 000 000 g mol-1 (less than 10%), 1 000 000 g mol-1 (about 40%), and 200 000 g mol-1 (about 50%). We have also observed a great retention of polymer during the filtration procedure, which is much pronounced as the AX concentration increases. This evidences the presence of large aggregates in the solution. The retention can be greatly diminished if the filtration is conducted under higher temperature. Aggregation could result from the establishment of intermolecular associations via hydrogen bonds. This hypothesis seems to be confirmed by the two higher populations in molar masses which present a random coil conformation consistent with a low degree of branching. Rheological measurements, conducted at 20 g L-1, have confirmed the association tendency leading to pseudo gels behavior. Viscoelastic properties have been evidenced by time−temperature master curves of dynamic spectra. Such master curves have also been established with addition of chaotropic (i.e., KSCN) and lyotropic (i.e., NaCl) salts. It has been shown that intermolecular associations are greatly diminished under chaotropic salts influence. This has been also confirmed by SEC/MALLS analysis. These results point out the role of hydrogen bonds in the organization of the AX system

Flax ( Linum usitatissimum ) Seed Cake: A Potential Source of High Molecular Weight Arabinoxylans?

International audienceWater-soluble polysaccharides were extracted from flaxseed cake and analyzed. Two groups were separated by anion-exchange chromatography. The first one (nonretained) was the major fraction (83%) and possessed a high molecular weight (HMW) arabinoxylan (56%) with an Ara/Xyl ratio of 0.32 and an Mw of 846 000. This polymer was accompanied by a smaller galactoglucan (44%), with an Mw of 6.5 × 104. The latter group (17%), retained by the gel, was further described as a HMW pectin heterogeneous group, with, respectively, 3.1 × 105 and 1.3 × 105. Despite the presence of HMW arabinoxylans, the investigation of rheological flow sweep at the concentration of 2% (w/v) has shown a slight shear thinning behavior with a small zero-rate viscosity at 9.6 Pa·s

Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression.

UnlabelledPancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low 5-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here, we report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates antitumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kγ in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8(+) T-cell-mediated tumor suppression and to inhibit tumor cell invasion, metastasis, and desmoplasia. These data indicate the central role that macrophage PI3Kγ plays in PDAC progression and demonstrate that pharmacologic inhibition of PI3Kγ represents a new therapeutic modality for this devastating tumor type.SignificanceWe report here that PI3Kγ regulates macrophage transcriptional programming, leading to T-cell suppression, desmoplasia, and metastasis in pancreas adenocarcinoma. Genetic or pharmacologic inhibition of PI3Kγ restores antitumor immune responses and improves responsiveness to standard-of-care chemotherapy. PI3Kγ represents a new therapeutic immune target for pancreas cancer. Cancer Discov; 6(8); 870-85. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 803

Macrophage PI3Kγ Drives Pancreatic Ductal Adenocarcinoma Progression

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low five-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here we report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates anti-tumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kγ in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8(+) T cell-mediated tumor suppression and to inhibit tumor cell invasion, metastasis and desmoplasia. These data indicate the central role that macrophage PI3Kγ plays in PDAC progression and demonstrate that pharmacological inhibition of PI3Kγ represents a new therapeutic modality for this devastating tumor type