| 1. |
- Huyghe, Jeroen R, et al.
(author)
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Genetic architectures of proximal and distal colorectal cancer are partly distinct
- 2021
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In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
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Journal article (peer-reviewed)abstract
- Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
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| 2. |
- Carter, Jodi M., et al.
(author)
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Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Journal article (peer-reviewed)abstract
- The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naive (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naive TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers.
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| 3. |
- Magallanes-Cruz, Perla A., et al.
(author)
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Effect of the addition of thermostable and non-thermostable type 2 resistant starch (RS2) in cake batters
- 2020
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In: LWT - Food Science and Technology. - : Elsevier BV. - 0023-6438.
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Journal article (peer-reviewed)abstract
- There is interest in increasing the consumption of foods with high dietary fiber content due to the health problems associated with its low intake. Plantain (Musa paradisiaca L.) flour (PF) (non-thermostable) and Hi-Maize 260 (HA) (thermostable) were used as resistant starch (RS) sources to elaborate blends with wheat (WF) and rice flours (RF) in a 50:50 ratio. Five blends were prepared (PF-WF, PF-RF, PF-HA, HA-WF and HA-RF) and used for batter formulations. Cakes were prepared with the batter blends. Rheological and thermal properties of batter, texture, total dietary fiber (TDF) and sensory analysis of cakes were evaluated. The batters with HA showed lower viscosity compared with PF batters. Cake texture was similar for the PF-RF, HA-WF and HA-RF. The highest TDF value in products “as eaten” was recorded in cakes with PF-HA and HA-RF, which agrees with the TDF value determined with a method that does not include RS, suggesting that the role of the food matrix is of importance for the carbohydrate digestibility. Sensory evaluation showed that consumers did not find differences between cakes despite being elaborated with different flour blends. The PF is an alternative to current commercial ingredients for the formulation of cakes with high TDF content.
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| 4. |
- Bello-Pérez, Luis A., et al.
(author)
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Starch digestibility: past, present and future
- 2020
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In: Journal of the Science of Food and Agriculture. - : Wiley. - 1097-0010 .- 0022-5142. ; 100, s. 5009-5016
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Research review (peer-reviewed)abstract
- In the last century, starch present in foods was considered to be completely digested. However, during the 1980s, studies on starch digestion started to show that besides digestible starch, which could be rapidly ors lowly hydrolysed, there was a variable fraction that resisted hydrolysis by digestive enzymes. That fraction was named resistant starch (RS )and it encompasses those forms of starch that are not accessible to human digestive enzymes but can be fermented by the colonic microbiota, producing short-chain fatty acids. RS has been classified into five types, depending on the mechanism governing its resistance to enzymatic hydrolysis. Early research on RS was focused on the methods to determine its content in foods and its physiological effects, including fermentability in the large intestine. Later on, due to the interest of the food industry, methods to increase the RS content of isolated starches were developed. Nowadays, the influence of RS on the gut microbiota is a relevant research topic owing to its potential health-related benefits. This review summarizes over 30 years of investigation on starch digestibility, its relationship with human health, the methods to produce RS and its impact on the microbiome.
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| 5. |
- Carmona-Garcia, Roselis, et al.
(author)
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Pregelatinised amaranth flour as an ingredient for low-fat gluten-free cakes
- 2022
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In: International Journal of Food Science and Technology. - : Wiley. - 0950-5423 .- 1365-2621. ; 57:4, s. 2346-2355
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Journal article (peer-reviewed)abstract
- This work explored the use of pregelatinised amaranth flour (PAF) as an oil substitute in the preparation of amaranth cakes. Amaranth flour was extruded to achieve approximately 50% gelatinisation, ground and sieved. The PAF was used to replace the oil in the cake preparation at levels 33, 66% and 100%. FTIR analysis of the cake formulations showed that PAF modified the molecular organisation of starch and proteins. The starch showed more hydrated structures, although less ordered. The proteins exhibited a significant reduction in the β structures and a marked increase of the side chains, probably caused by the interaction with amaranth starch. The in vitro digestibility of starch showed a slight increase with the addition of PAF. The slowly digesting starch fraction showed a visible decrease, reflecting the presence of starch chains more accessible to amylolysis. Instrumental texture revealed an increase (P < 0.05) in cake hardness with the addition of PAF, particularly for medium (66%) and high (100%) oil replacements. Sensory analysis showed that the perceived texture, flavour and colour were negatively affected by the addition of the pregelatinised flour. Overall, the sensory analysis indicated that cakes with low levels of PAF oil replacement may be acceptable to consumers.
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| 6. |
- El Bairi, Khalid, et al.
(author)
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The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
- 2021
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In: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
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Research review (peer-reviewed)abstract
- The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.
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| 7. |
- Garcia-Valle, Daniel E., et al.
(author)
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Effect of the preparation method on structural and in vitro digestibility properties of type II resistant starch-enriched wheat semolina pasta
- 2022
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In: Journal of Cereal Science. - : Elsevier BV. - 0733-5210. ; 106, s. 8-8
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Journal article (peer-reviewed)abstract
- The formulation of semolina pasta with reduced starch digestibility is of prime importance to deal with the adverse effects of the intake of rapidly digested carbohydrates on human health. This work focused on the effects of the production method (extrusion and lamination) and the addition of commercial Type 2 resistant starch (RS) on the molecular organization and in vitro starch digestibility of semolina pasta. Semolina was substituted with different levels of Type 2 RS for assessing the effect of this dietary fiber. The RS addition reduced the protein solubility and accessible thiols groups, with extruded pasta having higher protein solubility and lower accessible thiols than laminated pasta. Starch ordered structures increased with the RS addition. The increase of the RS in the pasta formulation resulted in a higher α-helix content and decreased β-sheet structures. In vitro starch digestibility was higher for extruded pasta, whilst the levels of RDS and SDS fractions decreased with the addition of RS. It was concluded that the preparation method in combination with RS addition has a determinant impact on the molecular organization and in vitro starch digestibility of semolina-based pasta, providing new insights on the possibilities of improving the health-beneficial features of this widely consumed product.
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