ObjectiveThis study aimed to describe and compare the nutritional status of adult patients submitted to allogeneic hematopoietic stem cell transplantation at two different time points (admission and discharge).MethodsA retrospective, descriptive and quantitative study was performed based on clinical, laboratory and nutritional data obtained from medical records of adult patients of both genders submitted to allogeneic hematopoietic stem cell transplantation in a bone marrow transplantation reference center in Rio de Janeiro in the period from 2010 to 2013. Statistical analysis was performed using the SPSS software (version 22.0).ResultsSixty-four patients were evaluated. The mean age was 42.1 ± 3.2 years and the most prevalent disease was acute myeloid leukemia (39%). There was a high prevalence of gastrointestinal symptoms including nausea (100%), vomiting (97%) and mucositis (93%). Between admission and discharge there was a significant decrease in the median weight (−2.5 kg; 71.5 vs. 68.75 kg; p-value < 0.001), body mass index (−0.9 kg/m2; 24.8 vs. 24.4 kg/m2; p-value < 0.001), and serum albumin levels (−0.2 g/dL; 3.7 vs. 3.6 g/dL; p-value = 0.024). The survival time after hematopoietic stem cell transplantation correlated negatively with C-reactive protein at discharge (CC = −0.72; p-value < 0.001) and positively with serum albumin levels (CC = 0.56; p-value = 0.004) and with high total protein level at discharge (CC = 0.53; p-value = 0.006).ConclusionOur results suggest that patients submitted to allogeneic hematopoietic stem cell transplantation have compromised nutritional status during the hospital stay for transplantation.

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Metabolic changes are commonly seen in cancer. Tumor cells present a high rate of glucose and glutamine uptake and part of these nutrients supplies the hexosamine biosynthesis pathway (HBP), whose exacerbation has been related to solid tumors progression, including colorectal cancer. Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the end product of HBP, serves as the donor for several enzymes involved in glycan biosynthesis. Aberrant glycosylation is known to affect cellular and molecular mechanisms related to the malignant phenotype. Beta 1,6-GlcNAc branches on N-glycans (products of the MGAT5 enzyme) are associated with greater stability of transmembrane glycoproteins, as glutamine and glucose transporters, and growth factor receptors. Furthermore, changes in the availability of UDP-GlcNAc can affect the levels of hyaluronic acid (HA) and O-GlcNAc-modified proteins. The interplay between different direct demands for UDP-GlcNAc is not well understood and may help to better understand tumor metabolism. Therefore, we intend to evaluate in colorectal cancer cells how changes in levels of branched beta1,6-GlcNAc N-glycans can affect both the hexosamine pathway and the different processes which demand UDP-GlcNAc (such as O-GlcNAcylation and hyaluronic acid synthesis). For this, two experimental strategies were performed. The first focused on the inhibition of complex N-glycans using swainsonine, and the second focused on the MGAT5 inactivation using CRISPR-Cas9. The levels of UDP-GlcNAc were also manipulated using DON, an inhibitor of the GFAT enzyme. Initially, it was found that both the pharmacological inhibition of complex N-glycan biosynthesis and the specific inactivation of MGAT5 lead to significantly reduced levels of hexosamine pathway intermediates, activated monosaccharides, and proteins modified by O-GlcNAc. Furthermore, it was also observed that MGAT5 inactivation enhances the expression of genes encoding HA synthases (HAS2 and HAS3). Upon detection of metabolites by LC-MS, a multivariate analysis was performed using the statistical method of Partial Least-Squares Discriminant Analysis (PLS-DA), and it was observed that KO MGAT5 cells formed a metabolically distinct population from MOCK cells. Interestingly, after pharmacological inhibition of GFAT, an increase in the levels of beta 1,6-GlcNAc branched N-glycans and a reduction in O-GlcNAcylation were observed. Treatment with DON was also able to reduce HAS2 expression however an increased in HAS3 expression was observed. These data suggest that there is a relationship among different demands for UDP-GlcNAc in tumor cells and a possible regulatory role played by beta 1,6-GlcNAc branched N-glycans in this issue. This work contributes to a better understanding of interconnections between biochemical processes that demand UDP-GlcNAc in the context of colorectal cancer. Citation Format: Érika Elias Ferreira, Isadora de Araújo Oliveira, Adriane Regina Todeschini, Julio Cesar de Freitas-Junior. The impact of beta 1,6-GlcNAc branched N-glycan synthesis on hexosamine pathway and UDP-GlcNAc demands in colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2387.