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Vongchan, P., M. Warda, H. Toyoda, T. Toida, R. M. Marks, and R. J. Linhardt, "Structural characterization of human liver heparan sulfate.", Biochimica et biophysica acta, vol. 1721, issue 1-3, pp. 1-8, 2005 Jan 18. Abstract

The isolation, purification and structural characterization of human liver heparan sulfate are described. 1H-NMR spectroscopy demonstrates the purity of this glycosaminoglycan (GAG) and two-dimensional 1H-NMR confirmed that it was heparan sulfate. Enzymatic depolymerization of the isolated heparan sulfate, followed by gradient polyacrylamide gel, confirmed its heparin lyase sensitivity. The concentration of resulting unsaturated disaccharides was determined using reverse phase ion-pairing (RPIP) HPLC with post column derivatization and fluorescence detection. The results of this analysis clearly demonstrate that the isolated GAG was heparan sulfate, not heparin. Human liver heparan sulfate was similar to heparin in that it has a reduced content of unsulfated disaccharide and an elevated average sulfation level. The antithrombin-mediated anti-factor Xa activity of human liver heparan sulfate, however, was much lower than porcine intestinal (pharmaceutical) heparin but was comparable to standard porcine intestinal heparan sulfate. Moreover, human liver heparan sulfate shows higher degree of sulfation than heparan sulfate isolated from porcine liver or from the human hepatoma Hep 2G cell line.

Vosoughi, A., T. Zhang, K. S. Shohdy, P. J. Vlachostergios, D. C. Wilkes, B. Bhinder, S. T. Tagawa, D. M. Nanus, A. M. Molina, H. Beltran, et al., "Common germline-somatic variant interactions in advanced urothelial cancer", Nature Communications, vol. 11, issue 1, pp. 6195 - 6195, 2020/12//. Abstract

The prevalence and biological consequences of deleterious germline variants in urothelial cancer (UC) are not fully characterized. We performed whole-exome sequencing (WES) of germline DNA and 157 primary and metastatic tumors from 80 UC patients. We developed a computational framework for identifying putative deleterious germline variants (pDGVs) from WES data. Here, we show that UC patients harbor a high prevalence of pDGVs that truncate tumor suppressor proteins. Deepening somatic loss of heterozygosity in serial tumor samples is observed, suggesting a critical role for these pDGVs in tumor progression. Significant intra-patient heterogeneity in germline-somatic variant interactions results in divergent biological pathway alterations between primary and metastatic tumors. Our results characterize the spectrum of germline variants in UC and highlight their roles in shaping the natural history of the disease. These findings could have broad clinical implications for cancer patients.

de Vries, N. L., V. van Unen, M. E. Ijsselsteijn, T. Abdelaal, R. van der Breggen, A. Farina Sarasqueta, A. Mahfouz, K. C. M. J. Peeters, T. Höllt, B. P. F. Lelieveldt, et al., "High-dimensional cytometric analysis of colorectal cancer reveals novel mediators of antitumour immunity.", Gut, 2019. Abstract

OBJECTIVE: A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC.

DESIGN: Thirty-six immune cell markers were simultaneously assessed at the single-cell level by mass cytometry in 35 CRC tissues, 26 tumour-associated lymph nodes, 17 colorectal healthy mucosa and 19 peripheral blood samples from 31 patients with CRC. Additionally, functional, transcriptional and spatial analyses of tumour-infiltrating lymphocytes were performed by flow cytometry, single-cell RNA-sequencing and multispectral immunofluorescence.

RESULTS: We discovered that a previously unappreciated innate lymphocyte population (LinCD7CD127CD56CD45RO) was enriched in CRC tissues and displayed cytotoxic activity. This subset demonstrated a tissue-resident (CD103CD69) phenotype and was most abundant in immunogenic mismatch repair (MMR)-deficient CRCs. Their presence in tumours was correlated with the infiltration of tumour-resident cytotoxic, helper and γδ T cells with highly similar activated (HLA-DRCD38PD-1) phenotypes. Remarkably, activated γδ T cells were almost exclusively found in MMR-deficient cancers. Non-activated counterparts of tumour-resident cytotoxic and γδ T cells were present in CRC and healthy mucosa tissues, but not in lymph nodes, with the exception of tumour-positive lymph nodes.

CONCLUSION: This work provides a blueprint for the understanding of the heterogeneous and intricate immune landscape of CRC, including the identification of previously unappreciated immune cell subsets. The concomitant presence of tumour-resident innate and adaptive immune cell populations suggests a multitargeted exploitation of their antitumour properties in a therapeutic setting.

Vural, A., H. Negm, and C. Vicini, "Rebotic Surgery of Skull Base", All Around the Nose: Springer, 2020.
Vwioko, E. D., M. A. El-Esawi, M. E. Imoni, A. A. Al-Ghamdi, H. M. Ali, M. M. El-Sheekh, E. A. Abdeldaym, and M. A. Al-Dosary, "Sodium Azide Priming Enhances Waterlogging Stress Tolerance in Okra (Abelmoschus esculentus L.)", Agronomy, vol. 9, no. 11: Multidisciplinary Digital Publishing Institute, pp. 679, 2019. Abstract
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