Journal articles on the topic 'Tumour associated carbohydrate'

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1

Toyokuni, Tatsushi, and Anil K. Singhal. "Synthetic carbohydrate vaccines based on tumour-associated antigens." Chemical Society Reviews 24, no. 4 (1995): 231. http://dx.doi.org/10.1039/cs9952400231.

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2

TOYOKUNI, T., and A. K. SINGHAL. "ChemInform Abstract: Synthetic Carbohydrate Vaccines Based on Tumour-Associated Antigens." ChemInform 27, no. 6 (August 12, 2010): no. http://dx.doi.org/10.1002/chin.199606316.

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3

Pinczower, Gideon D., Roderick P. W. Williams, Robert D. Gianello, H. Clem Robinson, Barry N. Preston, and Anthony W. Linnane. "Characterisation of the tumour-associated carbohydrate epitope recognised by monoclonal antibody 4D3." International Journal of Cancer 66, no. 5 (May 29, 1996): 636–44. http://dx.doi.org/10.1002/(sici)1097-0215(19960529)66:5<636::aid-ijc10>3.0.co;2-2.

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4

Hounsell, Elizabeth F., MIA Young, and Michael J. Davies. "Glycoprotein Changes in Tumours: A Renaissance in Clinical Applications." Clinical Science 93, no. 4 (October 1, 1997): 287–93. http://dx.doi.org/10.1042/cs0930287.

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1. Oligosaccharides linked to protein (glycoprotein) or lipid (glycolipid) are the major components at the outer surface of mammalian cells. Studies using antibodies and lectins have shown in the past that the oligosaccharides they recognize exhibit tumour-associated changes, i.e. they are carbohydrate tumour-associated antigens. 2. The oligosaccharides have been further characterized in recent years by structural analysis using high-resolution chromatographic techniques, MS and NMR. NMR gives an oligosaccharide fingerprint that is characteristic of monosaccharide type and linkage and which can be correlated with magnetic resonance spectroscopic data on fine-needle tissue aspirates. 3. Also of relevance is the new understanding of the molecular biology of MUC genes, which code for mucin protein backbones, and of the glycosyltransferase genes, which determine oligosaccharide structure and immunological recognition. 4. For these reasons, we believe that tumour-associated oligosaccharide changes should be revisited in the context of what we now know about structure and expression. This review synopsizes the past data using the detection of carbohydrate tumour-associated antigens by binding of lectins and antibodies, and puts it into the context of NMR fingerprints or signatures.
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PUTZ, E. F., and D. N. MANNEL. "Monocyte Activation by Tumour Cells: a Role for Carbohydrate Structures Associated with CD2." Scandinavian Journal of Immunology 41, no. 1 (January 1995): 77–84. http://dx.doi.org/10.1111/j.1365-3083.1995.tb03536.x.

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6

Franco, A. "CTL-Based Cancer Preventive/Therapeutic Vaccines for Carcinomas: Role of Tumour-Associated Carbohydrate Antigens." Scandinavian Journal of Immunology 61, no. 5 (May 2005): 391–97. http://dx.doi.org/10.1111/j.1365-3083.2005.01596.x.

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7

Nativi, Cristina, Francesco Papi, and Stefano Roelens. "Tn antigen analogues: the synthetic way to “upgrade” an attracting tumour associated carbohydrate antigen (TACA)." Chemical Communications 55, no. 54 (2019): 7729–36. http://dx.doi.org/10.1039/c9cc02920f.

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8

da Costa, Valeria, and Teresa Freire. "Advances in the Immunomodulatory Properties of Glycoantigens in Cancer." Cancers 14, no. 8 (April 7, 2022): 1854. http://dx.doi.org/10.3390/cancers14081854.

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Aberrant glycosylation in tumour progression is currently a topic of main interest. Tumour-associated carbohydrate antigens (TACAs) are expressed in a wide variety of epithelial cancers, being both a diagnostic tool and a potential treatment target, as they have impact on patient outcome and disease progression. Glycans affect both tumour-cell biology properties as well as the antitumor immune response. It has been ascertained that TACAs affect cell migration, invasion and metastatic properties both when expressed by cancer cells or by their extracellular vesicles. On the other hand, tumour-associated glycans recognized by C-type lectin receptors in immune cells possess immunomodulatory properties which enable tumour growth and immune response evasion. Yet, much remains unknown, concerning mechanisms involved in deregulation of glycan synthesis and how this affects cell biology on a major level. This review summarises the main findings to date concerning how aberrant glycans influence tumour growth and immunity, their application in cancer treatment and spotlights of unanswered challenges remaining to be solved.
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Saeland, Eirikur, and Yvette van Kooyk. "Highly glycosylated tumour antigens: interactions with the immune system." Biochemical Society Transactions 39, no. 1 (January 19, 2011): 388–92. http://dx.doi.org/10.1042/bst0390388.

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A common phenotypic change in cancer is a dramatic transformation of cellular glycosylation. Functional studies of particular tumour-associated oligosaccharides are difficult to interpret conclusively, but carbohydrate-binding proteins are likely to contribute to progression of the tumour. This review discusses the potential role of CLRs (C-type lectin receptors), expressed by antigen-presenting cells of the immune system, in tumour recognition and immune modulation. Studies in recent years have provided significant insight into the immunomodulatory function of CLR during infections, but their role in cancer remains elusive; some strongly bind tumour cells and antigens, indicating participation in malignancy. The potential to use recombinant CLR as diagnostic tools will also be discussed.
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10

Jiang, Bei-ge, Rui-liang Ge, Liang-liang Sun, Ming Zong, Gong-tian Wei, and Yong-jie Zhang. "Clinical Parameters Predicting Survival Duration after Hepatectomy for Intrahepatic Cholangiocarcinoma." Canadian Journal of Gastroenterology 25, no. 11 (2011): 603–8. http://dx.doi.org/10.1155/2011/917097.

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BACKGROUND: Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision.OBJECTIVE: To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration.METHODS: Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration.RESULTS: Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level >37 U/mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, repsectively.CONCLUSIONS: The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies.
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11

Toda, Munetoyo, Risa Hisano, Hajime Yurugi, Kaoru Akita, Kouji Maruyama, Mizue Inoue, Takahiro Adachi, Takeshi Tsubata, and Hiroshi Nakada. "Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells." Biochemical Journal 417, no. 3 (January 16, 2009): 673–83. http://dx.doi.org/10.1042/bj20081241.

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CD22 [Siglec-2 (sialic acid-binding, immunoglobulin-like lectin-2)], a negative regulator of B-cell signalling, binds to α2,6- sialic acid-linked glycoconjugates, including a sialyl-Tn antigen that is one of the typical tumour-associated carbohydrate antigens expressed on various mucins. Many epithelial tumours secrete mucins into tissues and/or the bloodstream. Mouse mammary adenocarcinoma cells, TA3-Ha, produce a mucin named epiglycanin, but a subline of them, TA3-St, does not. Epiglycanin binds to CD22 and inhibits B-cell signalling in vitro. The in vivo effect of mucins in the tumour-bearing state was investigated using these cell lines. It should be noted that splenic MZ (marginal zone) B-cells were dramatically reduced in the mice bearing TA3-Ha cells but not in those bearing TA3-St cells, this being consistent with the finding that the thymus-independent response was reduced in these mice. When the mucins were administered to normal mice, a portion of them was detected in the splenic MZ associated with the MZ B-cells. Furthermore, administration of mucins to normal mice clearly reduced the splenic MZ B-cells, similar to tumour-bearing mice. These results indicate that mucins in the bloodstream interacted with CD22, which led to impairment of the splenic MZ B-cells in the tumour-bearing state.
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12

Kunz, Horst, and Constanze Brocke. "Synthetic Glycopeptides of the Tandem Repeat Sequence of the Epithelial Mucin MUC4 with Tumour-associated Carbohydrate Antigens." Synlett, no. 13 (2003): 2052–56. http://dx.doi.org/10.1055/s-2003-42029.

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13

Feizi, T., and R. A. Childs. "Carbohydrate structures of glycoproteins and glycolipids as differentiation antigens, tumour-associated antigens and components of receptor systems." Trends in Biochemical Sciences 10, no. 1 (January 1985): 24–29. http://dx.doi.org/10.1016/0968-0004(85)90012-x.

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14

Steck, P. A., S. M. North, and G. L. Nicolson. "Purification and partial characterization of a tumour-metastasis-associated high-Mr glycoprotein from rat 13762NF mammary adenocarcinoma cells." Biochemical Journal 242, no. 3 (March 15, 1987): 779–87. http://dx.doi.org/10.1042/bj2420779.

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The expression of a high-Mr sialogalactoprotein (gp580) on rat 13762NF mammary adenocarcinoma cells was identified and correlated with spontaneous metastatic potential to colonize lung [Steck & Nicolson (1983) Exp. Cell Res. 147, 255-267]. Using a highly metastatic tumour-cell clone, MTLn3, we isolated and characterized gp580 from cells growing in vitro and in vivo in the mammary fat-pads of Fischer 344 rats. The glycoprotein was extracted with 4 M-guanidinium chloride/4% Zwittergent 3-12 solution in the presence of proteinase inhibitors. The extracts were then subjected to dissociative CsCl-density-gradient centrifugation, gel filtration on Sepharose CL-2B columns and ion-exchange chromatography on DEAE-Sephacel. The isolated glycoprotein possessed low electrophoretic mobility in SDS/polyacrylamide gels, and after desialylation bound 125I-labelled peanut agglutinin. Electrophoresis of gp580 in polyacrylamide-gradient gels resulted in a diffuse but homogeneous migrating band of Mr approx. 55,000. After removal of carbohydrate, gp580 was demonstrated to have a protein core of Mr approx. 150,000. The gp580 had a high density (1.430 g/ml) on isopycnic centrifugation in 4 M-guanidinium chloride and was resistant to most proteinases and other degradative enzymes, suggesting a mucin-like structure. Amino acid and carbohydrate analyses revealed that gp580 has high contents of serine, threonine, glutamic acid, aspartic acid, glucosamine and galactosamine; several acidic and neutral oligosaccharides were obtained from alkaline-borohydride digests. Cellular localization studies suggested that gp580 is associated mainly with the cell-surface and extracellular-matrix fractions of MTLn3 cells.
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15

Schwonzen, M., R. Schmits, SE Baldus, M. Vierbuchen, F.-G. Hanisch, M. Pfreundschuh, V. Diehl, J. Bara, and G. Uhlenbruck. "Monoclonal antibody FW6 generated against a mucin-carbohydrate of human amniotic fluid recognises a colonic tumour-associated epitope." British Journal of Cancer 65, no. 4 (April 1992): 559–65. http://dx.doi.org/10.1038/bjc.1992.114.

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16

Wang, Weikun, Paulina Sindrewicz-Goral, Chen Chen, Carrie A. Duckworth, David Mark Pritchard, Jonathan M. Rhodes, and Lu-Gang Yu. "Appearance of peanut agglutinin in the blood circulation after peanut ingestion promotes endothelial secretion of metastasis-promoting cytokines." Carcinogenesis 42, no. 8 (July 5, 2021): 1079–88. http://dx.doi.org/10.1093/carcin/bgab059.

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Abstract Peanut agglutinin (PNA) is a carbohydrate-binding protein in peanuts that accounts for ~0.15% peanut weight. PNA is highly resistant to cooking and digestion and is rapidly detectable in the blood after peanut consumption. Our previous studies have shown that circulating PNA mimics the actions of endogenous galactoside-binding protein galectin-3 by interaction with tumour cell-associated MUC1 and promotes circulating tumour cell metastatic spreading. The present study shows that circulating PNA interacts with micro- as well as macro-vascular endothelial cells and induces endothelial secretion of cytokines MCP-1 (CCL2) and IL-6 in vitro and in vivo. The increased secretion of these cytokines autocrinely/paracrinely enhances the expression of endothelial cell surface adhesion molecules including integrins, VCAM and selectin, leading to increased tumour cell-endothelial adhesion and endothelial tubule formation. Binding of PNA to endothelial surface MCAM (CD146), via N-linked glycans, and subsequent activation of PI3K-AKT-PREAS40 signalling is here shown responsible for PNA-induced secretion of MCP-1 and IL-6 by vascular endothelium. Thus, in addition to its influence on promoting tumour cell spreading by interaction with tumour cell-associated MUC1, circulating PNA might also influence metastasis by enhancing the secretion of metastasis-promoting MCP-1 and IL-6 from the vascular endothelium.
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17

Donohoe, Claire L., Aoife M. Ryan, and John V. Reynolds. "Cancer Cachexia: Mechanisms and Clinical Implications." Gastroenterology Research and Practice 2011 (2011): 1–13. http://dx.doi.org/10.1155/2011/601434.

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Cachexia is a multifactorial process of skeletal muscle and adipose tissue atrophy resulting in progressive weight loss. It is associated with poor quality of life, poor physical function, and poor prognosis in cancer patients. It involves multiple pathways: procachectic and proinflammatory signals from tumour cells, systemic inflammation in the host, and widespread metabolic changes (increased resting energy expenditure and alterations in metabolism of protein, fat, and carbohydrate). Whether it is primarily driven by the tumour or as a result of the host response to the tumour has yet to be fully elucidated. Cachexia is compounded by anorexia and the relationship between these two entities has not been clarified fully. Inconsistencies in the definition of cachexia have limited the epidemiological characterisation of the condition and there has been slow progress in identifying therapeutic agents and trialling them in the clinical setting. Understanding the complex interplay of tumour and host factors will uncover new therapeutic targets.
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18

Nagy, Csörsz, and Arvand Haschemi. "Sedoheptulose kinase regulates cellular carbohydrate metabolism by sedoheptulose 7-phosphate supply." Biochemical Society Transactions 41, no. 2 (March 21, 2013): 674–80. http://dx.doi.org/10.1042/bst20120354.

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Dynamic carbon re-routing between catabolic and anabolic metabolism is an essential element of cellular transformation associated with tumour formation and immune cell activation. Such bioenergetic adaptations are important for cellular function and therefore require tight control. Carbohydrate phosphorylation has been proposed as a rate-limiting step of several metabolic networks. The recent identification of a sedoheptulose kinase indicated that free sedoheptulose is a relevant and accessible carbon source in humans. Furthermore, the bioavailability of its phosphorylated form, sedoheptulose 7-phosphate, appears to function as a rheostat for carbon-flux at the interface of glycolysis and the pentose phosphate pathway. In the present paper, we review reports of sedoheptulose metabolism, compare it with glucose metabolism, and discuss the regulation of sedoheptulose kinase as mechanism to achieve bioenergetic reprogramming in cells.
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ZWERSCHKE, Werner, Sybille MAZUREK, Petra STÖCKL, Eveline HÜTTER, Erich EIGENBRODT, and Pidder JANSEN-DÜRR. "Metabolic analysis of senescent human fibroblasts reveals a role for AMP in cellular senescence." Biochemical Journal 376, no. 2 (December 1, 2003): 403–11. http://dx.doi.org/10.1042/bj20030816.

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Cellular senescence is considered a major tumour-suppressor mechanism in mammals, and many oncogenic insults, such as the activation of the ras proto-oncogene, trigger initiation of the senescence programme. Although it was shown that activation of the senescence programme involves the up-regulation of cell-cycle regulators such as the inhibitors of cyclin-dependent kinases p16INK4A and p21CIP-1, the mechanisms underlying the senescence response remain to be resolved. In the case of stress-induced premature senescence, reactive oxygen species are considered important intermediates contributing to the phenotype. Moreover, distinct alterations of the cellular carbohydrate metabolism are known to contribute to oncogenic transformation, as is best documented for the phenomenon of aerobic glycolysis. These findings suggest that metabolic alterations are involved in tumourigenesis and tumour suppression; however, little is known about the metabolic pathways that contribute to these processes. Using the human fibroblast model of in vitro senescence, we analysed age-dependent changes in the cellular carbohydrate metabolism. Here we show that senescent fibroblasts enter into a metabolic imbalance, associated with a strong reduction in the levels of ribonucleotide triphosphates, including ATP, which are required for nucleotide biosynthesis and hence proliferation. ATP depletion in senescent fibroblasts is due to dysregulation of glycolytic enzymes, and finally leads to a drastic increase in cellular AMP, which is shown here to induce premature senescence. These results suggest that metabolic regulation plays an important role during cellular senescence and hence tumour suppression.
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Lilo, Taha, Camilo L. M. Morais, Katherine M. Ashton, Ana Pardilho, Charles Davis, Timothy P. Dawson, Nihal Gurusinghe, and Francis L. Martin. "Spectrochemical differentiation of meningioma tumours based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy." Analytical and Bioanalytical Chemistry 412, no. 5 (December 21, 2019): 1077–86. http://dx.doi.org/10.1007/s00216-019-02332-w.

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AbstractMeningiomas are the commonest types of tumours in the central nervous system (CNS). It is a benign type of tumour divided into three WHO grades (I, II and III) associated with tumour growth rate and likelihood of recurrence, where surgical outcomes and patient treatments are dependent on the meningioma grade and histological subtype. The development of alternative approaches based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy could aid meningioma grade determination and its biospectrochemical profiling in an automated fashion. Herein, ATR-FTIR in combination with chemometric techniques is employed to distinguish grade I, grade II and grade I meningiomas that re-occurred. Ninety-nine patients were investigated in this study where their formalin-fixed paraffin-embedded (FFPE) brain tissue samples were analysed by ATR-FTIR spectroscopy. Subsequent classification was performed via principal component analysis plus linear discriminant analysis (PCA-LDA) and partial least squares plus discriminant analysis (PLS-DA). PLS-DA gave the best results where grade I and grade II meningiomas were discriminated with 79% accuracy, 80% sensitivity and 73% specificity, while grade I versus grade I recurrence and grade II versus grade I recurrence were discriminated with 94% accuracy (94% sensitivity and specificity) and 97% accuracy (97% sensitivity and 100% specificity), respectively. Several wavenumbers were identified as possible biomarkers towards tumour differentiation. The majority of these were associated with lipids, protein, DNA/RNA and carbohydrate alterations. These findings demonstrate the potential of ATR-FTIR spectroscopy towards meningioma grade discrimination as a fast, low-cost, non-destructive and sensitive tool for clinical settings.
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21

Minafra, S., C. Luparello, I. Pucci-Minafra, M. E. Sobel, and S. Garbisa. "Adhesion of 8701-BC breast cancer cells to type V collagen and 67 kDa receptor." Journal of Cell Science 102, no. 2 (June 1, 1992): 323–28. http://dx.doi.org/10.1242/jcs.102.2.323.

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Ductal infiltration carcinomas (d.i.c.) of the breast are potentially highly metastatic tumours, associated with drastic alterations of the architecture and molecular composition of the extracellular matrix at the tumour-host interface. 8701-BC, a recently characterized cell line, isolated from primary d.i.c., was used to study different aspects of tumor cell-substratum interactions. Since type V collagen deposition is augmented in d.i.c. we have examined the ability of 8701-BC cells to interact with this collagen species. We have found that cell binding to type V collagen was mediated by protein homologous to the 67 kDa laminin receptor (67-R). This conclusion is substantiated by the following observations: (a) a major band having an apparent molecular mass of 67 kDa and immunoreactive to the anti-67 R antibody was detectable by SDS-PAGE of the membrane proteins; (b) the antibody inhibited cellular adhesion to type V collagen in a dose-dependent way; (c) membrane proteins purified by affinity chromatography on type V collagen were immunoreactive to anti-67 R antibody, but not to anti-VLA1, VLA2 and VLA3 integrin antibodies. This receptor appears to have prominent carbohydrate-binding properties, since lactose competes with cell adhesion to type V collagen.
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22

Cao, Yinghao, Songqing Ke, Junnan Gu, Fuwei Mao, Shuang Yao, Shenghe Deng, Lizhao Yan, Ke Wu, Li Liu, and Kailin Cai. "The Value of Haematological Parameters and Tumour Markers in the Prediction of Intestinal Obstruction in 1474 Chinese Colorectal Cancer Patients." Disease Markers 2020 (August 14, 2020): 1–12. http://dx.doi.org/10.1155/2020/8860328.

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Intestinal obstruction, a life-threatening problem, often occurs in patients with advanced colorectal cancer (CRC). However, the cause of obstruction is still unknown. Very few prediction models for intestinal obstruction in CRC exist, and their results are unreliable. Therefore, we investigated whether preoperative serum tumour markers (STMs) combined with haematological and biochemical markers could be used as predictors. We retrospectively analysed 1474 patients with CRC who underwent radical resection after admission. Several clinical features, STMs, and serum biochemical and haematological indicators were analysed. Predictors of intestinal obstruction were analysed with univariate and multivariate logistic regression. The accuracy of the multivariate predictors of obstruction was measured by the area under the receiver operating characteristic (ROC) curve (AUC). The Kaplan-Meier method was used to create survival curves. Obstruction was found more in males (62.18%), never-smokers (73.95%), the left colon (54.20%), the tumour diameter>4.5 cm (55.88%), high differentiation (89.50%), and negative nerve invasion (70.17%). The serum tumour markers (STMs) and peripheral blood routine indexes (PBRI) were significantly associated with obstructive status (p<0.05). Multivariate analysis demonstrated that the neutrophil and lymphocyte counts, carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, albumin, alkaline phosphatase, gamma-glutamyl transpeptidase, total protein, and neutrophil-to-lymphocyte ratio were predictors of intestinal obstruction (p<0.05). The AUC for the curve with all the eight factors was 0.715 (95% confidence interval: 0.673-0.758). The STMs and PBRI were related to the obstruction status of the patients, and they could be used in combination with other clinical factors to significantly improve diagnosis and management of intestinal obstruction in CRC patients.
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BERGERON, Alain, Hélène LaRUE, and Yves FRADET. "Biochemical analysis of a bladder-cancer-associated mucin: structural features and epitope characterization." Biochemical Journal 321, no. 3 (February 1, 1997): 889–96. http://dx.doi.org/10.1042/bj3210889.

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Three monoclonal antibodies (mAbs), M344, M300 and M75, were shown to define a unique tumour-associated antigen (TAA) of superficial bladder tumours. The antigenic determinants are expressed on a very-high-molecular-mass component and, in about 50% of the positive samples, one determinant is also detected on a 62 kDa molecular species, observed only under reducing conditions. The objectives of the present study were to characterize further this TAA by analysing (1) the biochemical nature of the epitopes recognized by the three mAbs, and (2) the biochemical and structural features of the molecule bearing them. The antigenicity was resistant to heat denaturation, trypsin and α-chymotrypsin treatments but highly sensitive to papain and Pronase digestion. NaIO4 oxidation decreased reactivity to mAbs M344 and M300 but enhanced reactivity to mAb M75. The three determinants were insensitive to β-galactosidase and α-l-fucosidase but were sensitive to Vibrio choleraeneuraminidase. None of the three mAbs reacted with ovine, bovine or porcine submaxillary mucins. Deglycosylation with O-glycosidase or trifluoromethanesulphonic acid completely abolished the reactivity of the mAbs whereas N-glycosidase F deglycosylation had no appreciable effect. The presence on the molecule of cryptic Galβ(1→3)GalNAc as a major core disaccharide was demonstrated by a heterologous sandwich assay using mAb M75 and peanut agglutinin. Thiol reduction using β-mercaptoethanol increased mobility of the high-molecular-mass component in polyacrylamide gels. We thus conclude that mAbs M344 and M300 react with sialylated carbohydrate epitopes, and mAb M75 reacts with a partially cryptic and periodate-resistant sialylated epitope expressed on a typical secreted high-molecular-mass oligomeric mucin which we named MAUB for mucin antigen of the urinary bladder.
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Xu, Xin, Liang Li, and Xue-Ning Zhang. "Correlation analysis of preoperative magnetic resonance cholangiopancreatography and prognosis in hilar cholangiocarcinoma." Clinical and Investigative Medicine 42, no. 4 (December 29, 2019): E14—E21. http://dx.doi.org/10.25011/cim.v42i4.33113.

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Purpose: To determine the presence and extent of preoperative biliary obstructions, using magnetic resonance cholangiopancreatography (MRCP), and to determine the clinicopathological consequences of these obstructions in a group of 83 patients with hilar cholangiocarcinoma (HC). Methods: Fifty-five HC patients with biliary obstruction and 28 HC patients without biliary obstruction were included in the study. The associations between biliary obstruction (assessed using MRCP) and clinicopathological characteristics were analysed. Results: Patients with biliary obstruction had a higher liver function and serum carbohydrate antigen than those without biliary obstruction. The Bismuth-Corlette classification, tumour stage and lymph node metastasis were identified as independent relative factors of biliary obstruction, while differentiation and biliary obstruction were identified as independent factors of overall survival. Furthermore, the size of the tumour, differentiation and biliary obstruction were independent prognostic indicators of disease-free survival for HC patients. Conclusions: The presence and extent of preoperative biliary obstruction, measured by MRCP, was associated with aggressive clinicopathological features and indicated poor prognosis in HC patients
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Nakagoe, Tohru, Kiyoyasu Fukushima, Atsushi Nanashima, Terumitsu Sawai, Takashi Tsuji, Masaaki Jibiki, Hiroyuki Yamaguchi, et al. "Expression of Lewisa, Sialyl Lewisa, Lewisx, Sialyl Lewisx, Antigens as Prognostic Factors in Patients with Colorectal Cancer." Canadian Journal of Gastroenterology 14, no. 9 (2000): 753–60. http://dx.doi.org/10.1155/2000/149851.

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BACKGROUND: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Le)xantigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear.PURPOSE: To clarify the prognostic value of Lea, sialyl Lea, Lexand sialyl Lexexpression in colorectal carcinomas as prognostic factors after surgery.PATIENTS AND METHODS: Colorectal carcinoma samples from 101 patients with primary colorectal carcinoma who underwent surgical resection were subject to immunohistochemical analyses for Lea, sialyl Lea, Lexand sialyl Lexexpression with the respective monoclonal antibodies.RESULTS: Lea, sialyl Lea, Lexand sialyl Lexwere expressed in 69 (68.3%), 73 (72.3%), 66 (65.4%) and 76 (75.3%) carcinomas, respectively. The patients with sialyl Lex-expressing tumours had more advanced cancer than those with nonsialyl Lex-expressing tumours (P=0.0029). The survival time after surgery of patients with Lex- or sialyl Lex-expressing tumours was significantly shorter than the survival time of those with non-Lex- or nonsialyl Lex-expressing tumours, respectively (P=0.023 and P=0.0001, respectively). Cox’s regression analysis revealed that Lexand sialyl Lexexpression, separate from stage and histological type, were prognostic variables for patient survival (hazard ratio [HR] for sialyl Lex-positive expression to sialyl Lex-negative expression 2.90; HR for Lex-positive expression to Lex-negative expression 12.76 in stage I/IV, 0.63 in stage II and 1.69 in stage III).CONCLUSIONS: Lexexpression and sialyl Lexexpression in colorectal carcinomas are each associated with poor prognosis. These variables should be considered in the design of future trials.
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Bhobe, Daksha, Andrew Lang, Chris Warren, and Ayman Hassadia. "Mucinous borderline ovarian tumour with torsion and micro-invasion and associated with high serum level of carbohydrate antigen 19-9: a case report." Hong Kong Journal of Gynaecology, Obstetrics and Midwifery 21, no. 2 (July 21, 2021): 86–89. http://dx.doi.org/10.12809/hkjgom.21.2.03.

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27

Liu, Man, Jingying Zhou, Xiaoyu Liu, Yu Feng, Weiqin Yang, Feng Wu, Otto Ka-Wing Cheung, et al. "Targeting monocyte-intrinsic enhancer reprogramming improves immunotherapy efficacy in hepatocellular carcinoma." Gut 69, no. 2 (May 10, 2019): 365–79. http://dx.doi.org/10.1136/gutjnl-2018-317257.

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ObjectiveHepatocellular carcinoma (HCC), mostly developed in fibrotic/cirrhotic liver, exhibits relatively low responsiveness to immune checkpoint blockade (ICB) therapy. As myeloid-derived suppressor cell (MDSC) is pivotal for immunosuppression, we investigated its role and regulation in the fibrotic microenvironment with an aim of developing mechanism-based combination immunotherapy.DesignFunctional significance of MDSCs was evaluated by flow cytometry using two orthotopic HCC models in fibrotic liver setting via carbon tetrachloride or high-fat high-carbohydrate diet and verified by clinical specimens. Mechanistic studies were conducted in human hepatic stellate cell (HSC)-peripheral blood mononuclear cell culture systems and fibrotic-HCC patient-derived MDSCs. The efficacy of single or combined therapy with anti-programmed death-1-ligand-1 (anti-PD-L1) and a clinically trialled BET bromodomain inhibitor i-BET762 was determined.ResultsAccumulation of monocytic MDSCs (M-MDSCs), but not polymorphonuclear MDSCs, in fibrotic livers significantly correlated with reduced tumour-infiltrating lymphocytes (TILs) and increased tumorigenicity in both mouse models. In human HCCs, the tumour-surrounding fibrotic livers were markedly enriched with M-MDSC, with its surrogate marker CD33 significantly associated with aggressive tumour phenotypes and poor survival rates. Mechanistically, activated HSCs induced monocyte-intrinsic p38 MAPK signalling to trigger enhancer reprogramming for M-MDSC development and immunosuppression. Treatment with p38 MAPK inhibitor abrogated HSC-M-MDSC crosstalk to prevent HCC growth. Concomitant with patient-derived M-MDSC suppression by i-BET762, combined treatment with anti-PD-L1 synergistically enhanced TILs, resulting in tumour eradication and prolonged survival in the fibrotic-HCC mouse model.ConclusionOur results signify how non-tumour-intrinsic properties in the desmoplastic microenvironment can be exploited to reinstate immunosurveillance, providing readily translatable combination strategies to empower HCC immunotherapy.
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Martinez-Useros, Javier, and Jesus Garcia-Foncillas. "The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer." BioMed Research International 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/1869304.

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Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation inBRCA2gene.BRCA2mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carryingBRCA2mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to targetBRCA2.The present systematic review collects and analyses the role ofBRCA2alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.
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Coxhead, J. M., E. A. Williams, and J. C. Mathers. "DNA mismatch repair status may influence anti-neoplastic effects of butyrate." Biochemical Society Transactions 33, no. 4 (August 1, 2005): 728–29. http://dx.doi.org/10.1042/bst0330728.

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HNPCC (hereditary non-polyposis colon cancer) is an autosomal-dominant disorder characterized by early-onset CRC (colorectal cancer). HNPCC is most often associated with mutations in the MMR (mismatch repair) genes hMLH1, hMSH2, hMSH6 or hPMS2. The mutator phenotype of a defective MMR system is MSI (microsatellite instability), which also occurs in approx. 15–25% of sporadic CRC cases, where it is associated with the hypermethylation of the promoter region of hMLH1. Dietary factors, including excessive alcohol consumption, ingestion of red meat and low folate intake, may increase the risk of MSI high tumour development. In contrast, aspirin may suppress MSI in MMR-deficient CRC cell lines. Butyrate, a short-chain-fatty-acid end product of carbohydrate fermentation in the colon, shares a number of anti-neoplastic properties with aspirin, including inhibiting proliferation and inducing apoptosis of CRC cells. Recent in vitro studies suggest that physiological concentrations of butyrate (0.5–2 mM) may have more potent anti-neoplastic effects in CRC cell lines deficient in MMR, but mechanisms for such a differential response remain to be established.
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Fu, Meiting, Dexin Chen, Fuzheng Luo, Mengshu Li, Yadong Wang, Junsheng Chen, Aimin Li, and Side Liu. "Association of the tumour stroma percentage in the preoperative biopsies with lymph node metastasis in colorectal cancer." British Journal of Cancer 122, no. 3 (December 2, 2019): 388–96. http://dx.doi.org/10.1038/s41416-019-0671-7.

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Abstract Background Preoperative prediction of lymph node (LN) status is integral to determining the most appropriate treatment strategy for colorectal cancer (CRC). This study aimed to develop and validate a nomogram to predict LN metastasis in CRC preoperatively. Methods A total of 530 patients were enrolled and divided into training and validation cohorts. The tumour stroma percentage (TSP) of the preoperative biopsies was assessed. The risk factors for LN metastasis were selected, and a nomogram was constructed subsequently. The performance of the nomogram was assessed by using the AUROC and the calibration curve, and then validated in the validation cohort. Results High TSP was significantly associated with LN metastasis in both the training and validation cohorts. Computed tomography (CT)-reported T stage, CT-reported LN status, preoperative tumour differentiation, carcinoembryonic antigen, carbohydrate antigen 19-9 and TSP were independent predictors of LN metastasis in CRC. A nomogram incorporating the six predictors was constructed. The nomogram yielded good discrimination and calibration, with an AUROC of 0.846 (95% CI: 0.807−0.886) and 0.809 (95% CI: 0.745−0.872) in the training and validation cohorts, respectively. Conclusions Assessment of TSP in the preoperative biopsies provided additional information about the LN status. The nomogram was useful for tailored therapy in CRC preoperatively.
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Lin, Chi-Yu, Shin Nieh, Jacqueline Whang-Peng, and Jaulang Hwang. "Reciprocal expression of tumour-associated carbohydrate antigens (Tn/sTn) and nuclear factor-B serves as an indicator of the prognosis of oral squamous cell carcinoma." Journal for ImmunoTherapy of Cancer 1, Suppl 1 (2013): P58. http://dx.doi.org/10.1186/2051-1426-1-s1-p58.

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van der Wurff, A. A. M., J. ten Kate, P. T. J. Marx, E. P. M. van der Linden, C. C. L. Beek, F.-J. Bovelander, J. Dekker, et al. "Expression of a marker for colonic crypt base cells is correlated with poor prognosis in human colorectal cancer." Gut 42, no. 1 (January 1, 1998): 63–70. http://dx.doi.org/10.1136/gut.42.1.63.

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Background—There is a need for markers in colorectal cancer which will allow subclassification of stage groups into subgroups with high versus low risk of recurrent disease.Aims—To develop monoclonal antibodies that recognise antigens on immature crypt base cells, on the assumption that in a neoplasm undifferentiated but not the terminally differentiated cells will be responsible for tumour progression.Methods—Colon crypt cells which were isolated from human colonic mucosa by EDTA/EGTA incubation were studied. By stepwise harvesting, crypt base cell enriched fractions were obtained, and after incubation with antibodies against dominant antigens, used as immunogens.Results—Of one crypt base cell specific antibody (5E9), the reactive epitope appeared to be a non-terminal carbohydrate in the mucin O-glycans of the colon. The epitope did not seem to be colon specific, but was expressed in a variety of other tissues. In colorectal carcinomas, 5E9 immunoreactivity identified a subgroup of patients with a tendency for worse prognosis.Conclusion—A mucin associated maturation epitope was identified in colonic crypt base cells, the expression of which in Dukes’ stage B3 colorectal carcinoma may be associated with poor prognosis.
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Li, Weiyao, Miguel Gonzalez-Gonzalez, Lara Sanz-Criado, Nuria Garcia-Carbonero, Angel Celdran, Pedro Villarejo-Campos, Pablo Minguez, et al. "A Novel PiRNA Enhances CA19-9 Sensitivity for Pancreatic Cancer Identification by Liquid Biopsy." Journal of Clinical Medicine 11, no. 24 (December 9, 2022): 7310. http://dx.doi.org/10.3390/jcm11247310.

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Pancreatic cancer is one of the deadliest tumours worldwide, and its poor prognosis is due to an inability to detect the disease at the early stages, thereby creating an urgent need to develop non-invasive biomarkers. P-element–induced wimpy testis (PIWI) proteins work together with piwi-interacting RNAs (piRNAs) to perform epigenetic regulation and as such hold great potential as biomarkers for pancreatic cancer. PIWIL2 and PIWIL4 are associated with better prognosis, while PIWIL1 and PIWIL3 involvement appears to be associated with carcinogenesis. We aimed to discover PIWIL3- and PIWIL4-modulated piRNAs and determine their potential mechanisms in pancreatic cancer and the clinical implications. PIWIL3 or PIWIL4 was downregulated in pancreatic cancer-derived cell lines or in a non-tumour cell line. Differentially expressed piRNAs were analysed by next generation sequencing of small RNA. Nine fresh-frozen samples from solid human pancreases (three healthy pancreases, three intraductal papillary mucinous neoplasms, and three early-stage pancreatic cancers) were included in the sequencing analysis. Two piRNAs associated with PIWIL3 (piR-168112 and piR-162725) were identified in the neoplastic cells; in untransformed samples, we identified one piRNA associated with PIWIL4 (pir-366845). After validation in pancreatic cancer-derived cell lines and one untransformed pancreatic cell line, these piRNAs were evaluated in plasma samples from healthy donors (n = 27) or patients with pancreatic cancer (n = 45). Interestingly, piR-162725 expression identified pancreatic cancer patients versus healthy donors in liquid biopsies. Moreover, the potential of the serum carbohydrate antigen 19-9 (CA19-9) biomarker to identify pancreatic cancer patients was greatly enhanced when combined with piR-162725 detection. The enhanced diagnostic potential for the early detection of pancreatic cancer in liquid biopsies of these new small non-coding RNAs will likely improve the prognosis and management of this deadly cancer.
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A., Wilches Torres, Rojas Caraballo J., Sanabria E., Reyes MontaÑo E, FernÁndez Alonso Jl, Varrot A., Imberty A., and Vega N. "PURIFICATION AND BIOCHEMICAL CHARACTERIZATION OF A T/TN SPECIFIC LECTIN FROM LEPECHINIA BULLATA SEEDS (LAMIACEAE)." International Journal of Pharmacy and Pharmaceutical Sciences 9, no. 10 (November 1, 2017): 165. http://dx.doi.org/10.22159/ijpps.2017v9i11.21514.

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Objective: This study focused on purifying and characterizing a lectin from Lepechinia bullata (L. bullata) seeds, and determining its specificity towards tumour-associated carbohydrate-antigens.Methods: Pigments were removed by washing the seeds with NH4OH 0.1 M pH 9.4 and treating the crude extracts with Pectinex®. The purification procedure consisted of anion exchange chromatography on diethylaminoethyl (DEAE)-Sephadex followed by affinity chromatography. For the characterization, the phase was used polyacrylamide gel electrophoresis-sodium dodecyl sulphate (SDS-PAGE), isoelectric focusing, hemagglutination assays, enzyme-linked lectinosorbent assay (ELLA) and thermal shift assay (TSA).Results: 6.2 mg of lectin were obtained from 100 g of seeds. It was able to agglutinate enzymatically treated erythrocytes with a minimal required lectin concentration of 7 μg. ml-1. Strong binding to asialo bovine submaxillary mucine (aBSM) was determined, corroborating Tn recognition.The isoelectric focusing showed a unique band at pH 8.5. Lectin pure shown bands at 28, 48 and 93 kDa by SDS-PAGE, with an incomplete dissociation of the last species despite trying several reduction conditions. By preparative electrophoresis under different conditions, three species were observed too, in all fractions one band at 28 kDa on Tricine-PAGE in reducing and no reducing conditions were found.Amino acid composition, carbohydrate content, thermal stability and Ca2+and Mn2+requirements were determined. N-acetylgalactosamine (GalNAc) and desialylated mucins inhibited the agglutinant activity on human cells. Fetuin inhibited hemagglutination of rabbit erythrocytes.Conclusion: A new lectin was isolated and characterized from L. bullata seeds, it recognizes T/Tn antigen and shows some similarities with other Lamiaceae lectins.
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Jurek, Agnieszka, Paweł Krzesiński, Grzegorz Gielerak, Beata Uziębło-Życzkowska, Przemysław Witek, Grzegorz Zieliński, Anna Kazimierczak, and Robert Wierzbowski. "Cardiovascular risk in patients with Cushing’s disease – an interdisciplinary problem." Pediatria i Medycyna Rodzinna 17, no. 3 (September 30, 2021): 197–202. http://dx.doi.org/10.15557/pimr.2021.0045.

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Cushing’s disease is a chronic endogenous hypercortisolaemia associated with overproduction of adrenocorticotropic hormone by a pituitary adenoma, leading to multiple systemic complications that significantly increase morbidity and mortality, as well as reduce the quality of life as a result of prolonged tissue exposure to excess cortisol. Hypercortisolaemia in Cushing’s disease is associated with significant functional and constitutional disorders of the entire body. The consequences of chronic hypercortisolaemia include haemodynamic disorders associated with excessive vascular contraction and increased blood pressure, obesity, carbohydrate metabolism disorders, dyslipidaemia, and coagulopathies, which may contribute to significant cardiovascular remodelling. Cardiovascular disorders have a particular impact on long-term prognosis and quality of life in Cushing’s disease. If left untreated, Cushing’s disease significantly increases the cardiovascular risk and limits the treatment options for secondary organ complications. Cardiovascular mortality (myocardial infarction, heart failure, stroke) is several times higher in patients with Cushing’s disease than in the general population. Early diagnosis of the corticotropic pituitary tumour, as well as a thorough morphological and functional cardiovascular assessment seem essential in risk stratification. Normalisation of cortisol levels after combined neurosurgical and/or pharmacological treatment reduces mortality and the risk of cardiovascular and respiratory complications. The aim of this study is to present the complexity of clinical problems in patients with Cushing’s disease, who are in a particular need of interdisciplinary care.
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Pezzuto, Francesca, Francesco Izzo, Pasquale De Luca, Elio Biffali, Luigi Buonaguro, Fabiana Tatangelo, Franco Maria Buonaguro, and Maria Lina Tornesello. "Clinical Significance of Telomerase Reverse-Transcriptase Promoter Mutations in Hepatocellular Carcinoma." Cancers 13, no. 15 (July 27, 2021): 3771. http://dx.doi.org/10.3390/cancers13153771.

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Telomerase reactivation during hepatocarcinogenesis is recurrently caused by two point mutations occurring most frequently at the nucleotide −124 (95%) and occasionally at the nucleotide −146 (<5%) upstream of the TERT translational start site in hepatocellular carcinoma (HCC). In this study, we designed a droplet digital PCR (ddPCR) assay to detect TERT promoter (TERTp) nucleotide change G>A at position −124 and to quantify the mutant allele frequency (MAF) in 121 primary liver cancers, including 114 HCC along with 23 autologous cirrhotic tissues, five cholangiocarcinoma (CC), and two hepato-cholangiocarcinoma (HCC-CC). All cases were evaluated for tumour markers such as α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). We compared the sensitivity of ddPCR and Sanger sequencing and investigated the prognostic relevance of TERTp mutations. The TERTp G>A transition was identified in 63.6% and 52.1% of HCC samples by ddPCR and Sanger sequencing, respectively. One out of 23 (4.3%) peri-tumour tissues tested positive only by ddPCR. One out of five CC (20%) and none of the HCC-CC were found concordantly mutated by the two methods. The TERTp MAF ranged from 2% to 66%, and the large majority (85.5%) of mutated samples showed a value above 20%. A statistically significant correlation was found between TERTp mutation and tumour size (p = 0.048), while an inverse correlation was observed with CA19-9 levels (p = 0.0105). Moreover, HCC patients with TERTp −124A had reduced survival. In conclusion, the single nucleotide variation G>A at position −124 in TERTp, detected either by ddPCR or by Sanger sequencing, showed a remarkable high frequency in HCC. Such mutation is associated with lower levels of CA19-9 and reduced survival in HCC patients suggesting that the TERTp status may represent a distinct signature of liver cancer subgroups.
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Bhuyian, Rokanuzzaman, Mohammad Golam Azam, Md Abdur Rob, Tareq M. Bhuiyan, and Md Anisur Rahman. "Diagnostic Accuracy of Serum Carbohydrate Antigen 19-9 in Determining Etiology of Obstructive Jaundice." BIRDEM Medical Journal 7, no. 2 (May 4, 2017): 95–100. http://dx.doi.org/10.3329/birdem.v7i2.32443.

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Background: Serum carbohydrate antigen 19-9 (CA 19-9), a tumour marker for malignancies of the hepatobiliary tract and pancreas, frequently elevated in a number of non-malignant conditions that are associated with jaundice. The CA 19-9 tends to normalize following the restoration of biliary drainage. This study was designed to assess the clinical application of CA19-9 in diagnosing pancreatobiliary malignancies in patients with obstructive jaundice and in discriminating between benign and malignant causes.Methods: Sixty three patients presented with obstructive jaundice on the basis of clinical, biochemical and imaging methods with elevated CA 19-9 were included in this study. Serum CA 19-9 levels were measured on admission and two weeks following endoscopic biliary drainage performed through an ERCP procedure at the department of Gastrointestinal, hepatobiliary and pancreatic disorders (GHPD) of BIRDEM general hospital. Malignant and benign cases were differentiated by ultrasonogram, CT scan, MRCP and morphological findings during ERCP procedure. Diagnostic accuracy of CA19-9 in the detection of malignancy was estimated by the receiver operating characteristic (ROC) curve.Results: Age was 53.76±14.48 years (mean±SD) and sex was 32:31 (M:F). Median value of CA 19-9 in malignant cases was higher (1000 U/ml) than benign cases (93 U/ml) (p=0.001). After biliary drainage serum CA19-9 levels normalized in 15(50%) benign and 1(3%) malignant cases (p=0.001). The AUC of CA 19-9 was 0.825. Sensitivity, specificity, PPV and NPV at cut off value 90 U/ml were 100, 50, 68.8 and 100; at 100 U/ml were 100, 53.3, 70.2 and 100; at 200 U/ml were 90.9, 66.7, 75 and 87, at 500 U/ml were 63.6, 76.7,75 and 65.7 respectively. Diagnostic accuracy of CA 19-9 was observed more at cut off value 200 U/ml.Conclusions: Deranged CA19-9 is frequently observed in benign conditions with jaundice and shown to normalize following improvement of biliary drainage. Caution is necessary in the interpretation of an elevated serum CA 19-9 value as a marker for malignancy, especially in patients with benign cholestasis.Birdem Med J 2017; 7(2): 95-100
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Mirzoeva, L. A., N. G. Nikiforov, V. A. Aladinsky, I. A. Sobenin, L. V. Nedosugova, and A. N. Orekhov. "Enhanced spontaneous and induced secretion of the proinflammatory cytokine TNF-alpha by monocytes-macrophages from the blood of the patients presenting with type 2 diabetes mellitus." Problems of Endocrinology 60, no. 5 (October 15, 2014): 22–25. http://dx.doi.org/10.14341/probl201460522-25.

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Type 2 diabetes mellitus (DM2) is known to be associated with the accelerated development of atherosclerosis. The current concepts of atherosclerosis take into consideration the possible role of inflammation in its pathogenesis which theoretically implies the modification of macrophages in accordance with the proinflammatory phenotype and the production of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-α) by these cells. In connection with this, we undertook a study of spontaneous and induced secretion of proinflammatory cytokine TNF-α by monocytes-macrophages from the blood of 20 patients presenting with newly diagnosed type 2 diabetes mellitus (HbA1c - 8,9%) and the healthy volunteers showing up no disturbances of carbohydrate metabolism. It was shown that blood monocytes-macrophages of the patients presenting with DM2 are characterized by the enhanced ability (compared with the cells from the healthy subjects) to synthesize TNF-α in both native and interferon-y stimulated states up to 750 versus 270 pg/ml culture medium and to 1653 pg/ml versus 378 pg/ml culture respectively. This difference was statistically significant (p <0.05). It is concluded that the results of the study help to explain the elevated blood TNF-α level in the patients with type 2 diabetes mellitus and provide an insight into the mechanism underlying the development of the systemic inflammatory reaction accelerating the progression of atherosclerosis associated with diabetes mellitus.
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Maryam Qussay Issa, Shatha MJ AL-Khateeb, Hala Sameh Arif, and Muhi Kadhem AL-Janabi. "The validity of carbohydrate antigen 19-9 in serum and saliva as a new type for diagnosis in Iraqi kids having cystic fibrosis." International Journal of Research in Pharmaceutical Sciences 10, no. 2 (April 23, 2019): 1440–43. http://dx.doi.org/10.26452/ijrps.v10i2.713.

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Cystic fibrosis is a life-limiting, recessive disease; it occurs due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Carbohydrate antigen 19-9 (CA19.9) is a tumour-associated, primarily occur in patients having biliary tract and pancreatic cancers but are also observed in patients having other malignancies. Conditions related to benign like cholestasis, cirrhosis, cholangitis, plus pancreatitis also result in CA 19-9 elevations. Raised levels of serum CA 19-9 seems in CF patient to be related to disease pulmonary exacerbation also in the lung the amount of sputum. Investigate whether serum and saliva (CA19.9) level may contribute to cystic fibrosis diagnosis establishment in patients. This "case-control study" consists of 80 individuals (30 patients and 50 healthy controls). Their age was range between one month and 18 years. Blood and saliva samples were taken from patients. Saliva level in patients was 1.775±1.030U/ml (P<0.001) as compared to control group (0.956±0.682 U/ml). A serum level of CA19.9 was found to be increased (P<0.001) by 0.818±0.601 U/ml in CF patients as compared to healthy (0.334±0.101 U/ml) control. From this study, we can conclude that the salivary CA19.9 level can be diagnosed as a marker for cystic fibrosis.
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Dabelsteen, E., and H. Clausen. "Tumor-associated carbohydrate antigens." Journal of Oral Pathology & Medicine 16, no. 4 (July 13, 2007): 196–98. http://dx.doi.org/10.1111/j.1600-0714.1987.tb02066.x.

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Hebbar, Shripad, and Vijaya Bharathi K. "Validation of a new ovarian malignancy suspicion index for preoperative evaluation of adnexal masses." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 6, no. 1 (December 20, 2016): 240. http://dx.doi.org/10.18203/2320-1770.ijrcog20164666.

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Background: The currently available ovarian malignancy probability scores incorporate biochemical markers such as CA 125 (Carbohydrate Antigen 125), which is not routinely available in peripheral centers. There is a need for tumour marker independent prediction model to differentiate malignant ovarian masses from their benign counterparts in order to plan appropriate surgery. To formulate and prospectively validate a new Ovarian Malignancy Suspicion Index (OMSI) independent of serum CA 125 level, in preoperative evaluation of adnexal masses admitted for surgery.Methods: This was a combined retrospective and prospective cohort study conducted in a tertiary referral hospital over a period of one and half years. Retrospective sample included 100 subjects who had undergone surgery for adnexal masses and who had definite histopathological report. Detailed data were obtained with respect to age, menopausal status, sonographic findings including solid areas, ascites, mean diameter, bilateralism, and presence of septa. A logistic multivariate regression analysis was carried out to find the best prediction score (OMSI - Ovarian Malignancy Suspicion Index). This model was further evaluated prospectively in 60 subjects for its diagnostic ability to identify benign and malignant ovarian pathology.Results: OMSI at the cut off value of 3.9 differentiated effectively malignant ovarian mass from benign variety with a good diagnostic performance (Sensitivity 100%, Specificity 90.5%, Positive Predictive Value 81.8% and Negative Predictive Value 100%) as good as currently recommended RMI (Risk Malignancy Index) score. It was also found that OMSI > 3.9 was associated with positive ultrasound evidence for ovarian malignancy such as presence of thick septae (90%), solid areas within the tumour (93.8%), papillary projections (100%), bilaterality (90%) and ascites (100%).Conclusions: This study shows that it is possible to derive ovarian malignancy prediction model such as OMSI without including CA 125 with diagnostic ability in par with risk scoring systems such as WHO recommended RMI. Using this model, physicians working in peripheral centers without facilities for estimating serum tumour markers can arrive at the possible diagnosis and plan appropriate management strategies.
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Mitchell, Paul Leslie, Shane Battye, Tom John, Carmel Murone, Simon Knight, Gerd Bode, Andreas Schroeder, and Khashayar Asadi. "Mucin 1 (MUC1) expression in patients (pts) with early stage non-small cell lung cancer (NSCLC): Relationship between immunohistochemistry (IHC), tumor characteristics, and survival." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 3011. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3011.

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3011 Background: MUC1, a glycoprotein highly expressed in many malignancies, is being explored as an antigen for immunotherapy. How best to measure MUC1 expression as well as its prognostic value in NSCLC are still under discussion. Methods: TMAs were constructed using triplicate 1mm cores of FFPE tumour and stained with 214D4 (recognises protein core) and MA695 (recognises carbohydrate epitope) anti-MUC1 antibodies (abs). TMAs were assessed for polarisation, both cyto and mem staining intensity (scored 0-3) and proportion cells +ve (0-100%; scored 0–5), averaged for multiple cores. A composite score (intensity x cells +ve) was derived, ranging from 0–15 (3+ in >75% cells). Results: TMAs from 521 pts were analysed: male 362 (69.5%); never smoking 35 (7%); adeno 259 (49.7%), squamous 180 (34.5%), large cell 39 (7.5%); nodal N0 340 (65.3%), N1 71 (13.6%), N2 107 (20.5%). Results of IHC staining intensity, proportion positive cells and depolarisation were very similar for the two abs. There was high concordance in the composite score for the abs (R2=0.71, p<0.0001). Polarisation was discordant in 7.9% of cases. For 77 cases with paired primary/ N2 nodal tissue, mean 214D4 scores were 8.3 and 8.9 and MA695 10.6 and 9.9 respectively. Discordant staining in primary but not in node was seen in 5.2% and 10.4% with 214D4 and MA695 respectively. Increased expression as assessed by 214D4 (HR=1.26; 95% CI 1.014-1.565, p=0.04 log rank test) and MA695 (HR=1.20, 95% CI 1.042-1.605; p=0.02) was associated with improved survival. The prognostic value of depolarisation has yet to be analyzed. Conclusions: Over 93% of cases were MUC1 IHC positive. Composite scores for the 2 abs were highly correlated and depolarisation largely concordant. MUC1 expression was generally maintained in paired primary/nodal tumour. Increased expression of MUC1 was associated with improved survival however further investigation is needed to determine which abs best predict outcomes. [Table: see text]
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Temme, J. Sebastian, Dorothy L. Butler, and Jeffrey C. Gildersleeve. "Anti-glycan antibodies: roles in human disease." Biochemical Journal 478, no. 8 (April 21, 2021): 1485–509. http://dx.doi.org/10.1042/bcj20200610.

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Carbohydrate-binding antibodies play diverse and critical roles in human health. Endogenous carbohydrate-binding antibodies that recognize bacterial, fungal, and other microbial carbohydrates prevent systemic infections and help maintain microbiome homeostasis. Anti-glycan antibodies can have both beneficial and detrimental effects. For example, alloantibodies to ABO blood group carbohydrates can help reduce the spread of some infectious diseases, but they also impose limitations for blood transfusions. Antibodies that recognize self-glycans can contribute to autoimmune diseases, such as Guillain-Barre syndrome. In addition to endogenous antibodies that arise through natural processes, a variety of vaccines induce anti-glycan antibodies as a primary mechanism of protection. Some examples of approved carbohydrate-based vaccines that have had a major impact on human health are against pneumococcus, Haemophilus influeanza type b, and Neisseria meningitidis. Monoclonal antibodies specifically targeting pathogen associated or tumor associated carbohydrate antigens (TACAs) are used clinically for both diagnostic and therapeutic purposes. This review aims to highlight some of the well-studied and critically important applications of anti-carbohydrate antibodies.
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Peltonen, Reetta, Pia Österlund, Marko Lempinen, Arno Nordin, Ulf-Håkan Stenman, and Helena Isoniemi. "Postoperative CEA is a better prognostic marker than CA19-9, hCGβ or TATI after resection of colorectal liver metastases." Tumor Biology 40, no. 1 (January 2018): 101042831775294. http://dx.doi.org/10.1177/1010428317752944.

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Liver metastases of colorectal cancer can be operated with a curative intent in selected cases. However, more than half of the patients have a recurrence. The aim of this study was to evaluate the prognostic and predictive value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), human chorionic gonadotropin β (hCGβ) and tumour-associated trypsin-inhibitor (TATI) in colorectal cancer patients before and 3 months after resection of liver metastases. Marker concentrations were determined in blood samples from 168 colorectal cancer patients, who underwent liver resection between the years 1998 and 2007 at Helsinki University Hospital, Finland. The samples were taken before and 3 months after curative resection. Increased concentrations of CEA (>5 µg/L) and hCGβ (>1 pmol/L) 3 months after liver resection correlated with recurrence and impaired overall survival and increased CA19-9 (>26 kU/L) with impaired overall survival, but postoperative TATI was not prognostic. Preoperatively elevated CEA and CA19-9 correlated with impaired overall survival, but not with recurrence. Neither preoperative hCGβ nor TATI was prognostic. In conclusion, CEA is a useful prognostic marker, when measured 3 months after resection of colorectal liver metastases. CA19-9 also has prognostic significance and may have additional value.
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Matsumoto, Yasuyuki. "Tumor-Associated Carbohydrate Antigens Targeting Immunotherapy." Trends in Glycoscience and Glycotechnology 33, no. 192 (March 25, 2021): J33—J38. http://dx.doi.org/10.4052/tigg.2009.1j.

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Matsumoto, Yasuyuki. "Tumor-Associated Carbohydrate Antigens Targeting Immunotherapy." Trends in Glycoscience and Glycotechnology 33, no. 192 (March 25, 2021): E33—E38. http://dx.doi.org/10.4052/tigg.2009.1e.

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47

Çöl, Ramazan, and Zafer Durgun. "Effect of recombinant interleukin-10 on some haematological and biochemical parameters in a rat endotoxaemic model." Acta Veterinaria Hungarica 59, no. 2 (June 1, 2011): 237–45. http://dx.doi.org/10.1556/avet.2011.009.

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Recombinant interleukin-10 (rIL10) has been found to suppress the synthesis of tumour necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6) and tissue factor and to improve survival from experimental sepsis. The aim of this study was to evaluate the protective effect of rIL-10 on lipopolysaccharide-(LPS-) induced haematological and biochemical disturbances in rats. In the present study, 40 rats were used and divided equally into four groups. Group 1 (control group, C) was treated with 0.9% saline. Group 2: LPS was injected intravenously (1.6 mg/100 g), Group 3 received rIL10 treatment (125 μg/kg) 2 min before 0.9% saline injection, Group 4 received rIL10 treatment 2 min before endotoxin treatment. When compared with the controls, platelet count, leukocyte count (with a marked neutrophilia and lymphopenia) and fibrinogen were decreased, while activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged in the endotoxaemic rats. In addition, LPS caused statistically significant increases in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as creatinine, cholesterol and triglyceride concentrations, while it caused a statistically significant decrease in glucose, total protein and albumin levels as compared to the control group. On the other hand, rIL10 significantly suppressed disturbances in the haematological and biochemical parameters associated with endotoxaemia. As a result, rIL10 may be efficacious in preventing haematological disorders, tissue damage and changes in lipid, protein and carbohydrate metabolism in endotoxaemia.
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Padler-Karavani, Vered, Eliran Moshe Reuven, Shani Leviatan Ben-Arye, Hai Yu, Roberto Duchi, Andrea Perota, Sophie Conchon, Jean-Paul Soulillou, Cesare Galli, and Xi Chen. "Active cancer vaccine targeting carbohydrates for immunotherapy." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 70.14. http://dx.doi.org/10.4049/jimmunol.202.supp.70.14.

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Abstract Transformed cells present cell surface neoantigens, including aberrantly expressed carbohydrates. Targeting tumor-associated carbohydrate antigens could be useful for cancer immunotherapy. N-glycolylneuraminic acid (Neu5Gc) is a non-human carbohydrate consumed in diet and accumulates on human cancer cells, leading to expression of neoantigens. Passive immunotherapy with anti-Neu5Gc antibodies in mice inhibits tumor growth. Here we describe an active cancer vaccination immunotherapy strategy to target Neu5Gc-positive tumors. We generated glyconanoparticles from engineered red blood cells to form nano-ghosts (NGs) that either express (NGpos) or lack expression (NGneg) of Neu5Gc-glycoconjugates. We then show that optimized immunization of Neu5Gc-deficient Cmah-KO mice with NGpos glyconanoparticles induce a robust, diverse and long-lasting anti- Neu5Gc IgG immune response. Anti-Neu5Gc IgG antibodies also migrated into Neu5Gc-positive tumors and inhibited tumor growth in-vivo. Using glycan microarrays we also show that the kinetics and quality of the immune responses influence the efficacy of the vaccine. Hence, immunotherapy targeting Neu5Gc-carbohydrate neoantigens is promising.
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Hakomori, Sen-itiroh. "Possible functions of tumor-associated carbohydrate antigens." Current Opinion in Immunology 3, no. 5 (October 1991): 646–53. http://dx.doi.org/10.1016/0952-7915(91)90091-e.

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50

Rodrigues Mantuano, Natalia, Marina Natoli, Alfred Zippelius, and Heinz Läubli. "Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy." Journal for ImmunoTherapy of Cancer 8, no. 2 (October 2020): e001222. http://dx.doi.org/10.1136/jitc-2020-001222.

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During oncogenesis, tumor cells present specific carbohydrate chains that are new targets for cancer immunotherapy. Whereas these tumor-associated carbohydrates (TACA) can be targeted with antibodies and vaccination approaches, TACA including sialic acid-containing glycans are able to inhibit anticancer immune responses by engagement of immune receptors on leukocytes. A family of immune-modulating receptors are sialic acid-binding Siglec receptors that have been recently described to inhibit antitumor activity mediated by myeloid cells, natural killer cells and T cells. Other TACA-binding receptors including selectins have been linked to cancer progression. Recent studies have shown that glycan-lectin interactions can be targeted to improve cancer immunotherapy. For example, interactions between the immune checkpoint T cell immunoglobulin and mucin-domain containing-3 and the lectin galectin-9 are targeted in clinical trials. In addition, an antibody against the lectin Siglec-15 is being tested in an early clinical trial. In this review, we summarize the previous and current efforts to target TACA and to inhibit inhibitory immune receptors binding to TACA including the Siglec-sialoglycan axis.
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