Overexpression of glutamine synthetase in human primary liver cancer

Christa, Laurence; Simón, Marina; Flinois, Jean‐Pierre; Gebhardt, Rolf; Bréchot, Christian; Lasserre, Chantal

doi:10.1016/0016-5085(94)90024-8

Cited by 89 publications

(63 citation statements)

References 21 publications

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“…51 Most importantly, GS is a target gene of ␤-catenin so that its overexpression is associated with mutations of ␤-catenin or with activation of this pathway. [52][53][54] Up-regulation of GS messenger RNA, protein, and activity were shown by Christa et al 52 in human HCC, while Osada et al 55 reported the stepwise increase in GS immunoreactivity from precancerous lesions to early HCC to progressed HCC. The monoclonal antibody from Chemicon International (clone MB302) at a dilution of 1/500 to 1/1000 and amplified with a new short polymer system yields reliable results.…”

Section: Emerging Tumor Markersmentioning

confidence: 94%

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

2008

Hepatology

713

238

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Section: Emerging Tumor Markersmentioning

confidence: 94%

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

2008

Hepatology

713

238

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“…matic activities of G6P, LDH, SDH, ND, HBDH, and GDH, Immunohistochemical Analysis of the Distribution of GLS. A crossimmunohistochemistry for the demonstration of the GLS pro-reacting rabbit polyclonal antibody was raised against recombinant tein, and in situ hybridization for the demonstration of albu-human GLS as previously described 23 and used in an indirect immumin messenger RNA (mRNA).…”

mentioning

confidence: 99%

The metabolic organization of the adult human liver: A comparative study of normal, fibrotic, and cirrhotic liver tissue

et al. 1996

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The mammalian hepatic lobule is characterized by a Little is known about the alterations of metabolic ormarked functional heterogeneity. [1][2][3] According to their posiganization of the human liver tissue in chronic liver distion within the hepatic lobule, hepatocytes present signifieases. We therefore compared the distribution of the folcant differences in the level of many enzyme activities, such lowing zonal metabolic markers in 10 samples of normal as those involved in the carbohydrate, ammonia, lipid, and liver tissue, 10 samples of fibrotic tissue, and 22 samples xenobiotic metabolisms, 2-5 and in the expression of some seof cirrhotic tissue: (a) the enzymatic activities of glucosecreted products, such as plasma proteins. 6 The metabolic or-6-phosphatase (G6P), lactate dehydrogenase (LDH), ganization of the mammalian hepatic lobule is well exemplisuccinate dehydrogenase (SDH), nicotinamide-adeninefied in the rat. In this species, gluconeogenesis, fatty acid dinucleotide-phosphate [NADPH] dehydrogenase (ND), oxydation, ureagenesis, and albumin synthesis predominate b-hydroxybutyrate dehydrogenase (HBDH), and glutamate dehydrogenase (GDH); (b) the protein glutamine in the periportal region of the hepatic lobule, while glycolysis, synthetase (GLS); and (c) albumin messenger RNA fatty acid synthesis, glutamine formation, and xenobiotic me-(mRNA). The normal human hepatic lobule was charac-tabolism predominate in the perivenous region. 7 The metaterized by the periportal predominance of G6P and SDH bolic zonation of the mammalian hepatic lobule is thought to enzymatic activities and albumin mRNAs, the perive-play an important physiological role by enabling the liver to nous predominance of ND and GDH, the restriction of simultaneously perform anabolic and catabolic activities, and GLS to a small perivenous compartment, and the pre-by allowing quick responses of the hepatic parenchyma to dominance of b-HBDH at the contact of both portal changes in the physiological status. 2,3,8 It is currently tracts and centrilobular veins. In fibrosis, the overall thought 2,3,8 that the maintenance of the metabolic organizametabolic organization of the normal liver tissue was tion of the liver depends mainly on microenvironmental facretained. The expression of periportal markers predomi-tors, including: (a) blood-borne factors, such as the gradients nated around enlarged portal tracts and that of perive-in oxygen, substrates, and hormones determined by the uninous markers around residual centrilobular veins. GLS directional perfusion of the hepatic lobule by the portal blood was constantly detected at the contact of centrilobular flow, (b) pericellular factors, such as the zonal differences in veins. In cirrhotic nodules, no zonation was observed the pattern of innervation, the composition of the extracellufor most enzymatic activities or for albumin. Only G6P lar matrix, and the functional characteristics of nonparenchyusually predominated at the periphery of the nodules. mal liver cells; and possibly (c) paracrine interac...

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“…Because such thickened trabecular structure cannot mix with noncancerous tissue, advanced HCCs show distinct margin even in a liver with an early stage of chronic liver disease. Various tumor markers, that is, HSP70, GPC3, and GS, also show incrementally more intense expression from early to advanced HCCs [25][26][27][28][29][30][31]. Vascularities of the tumors also change according to tumor development.…”

Section: Developmental Process Of Hccs From Early Stage To Advanced Smentioning

confidence: 99%

“…In addition to the morphological criteria, some attempts have been made recently to utilize immunohistochemical markers for the diagnosis of well-differentiated HCCs [25][26][27][28][29][30][31]. Heat shock protein 70 (HSP70) [25,26], glypican 3 (GPC3) [25,[27][28][29], and glutamine synthetase (GS) [25,30,31] have been used independently or in combination.…”

Section: Total Process Of Biopsy Diagnosismentioning

confidence: 99%

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Histological features of early hepatocellular carcinomas and their developmental process: for daily practical clinical application

Kondo

2008

Hepatol Int

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Based on clinical and pathological experience, indistinct margin-type hepatocellular carcinomas (HCCs) were considered to be typical early-stage HCCs with good prognosis. For histological diagnosis, the assessment of stromal invasion (tumor invasion into portal tracts and fibrous septa) is very important. In differentiating stromal invasion from pseudoinvasion (benign hepatic tissue in the fibrous stroma), the following 5 items are useful: (1) macroscopic or panoramic views of the histological specimen, (2) amount of fibrous components of the stroma, (3) destruction of the structure of portal tracts, (4) loss of reticulin fibers around cancer cells, and (5) cytokeratin 7 immunostaining for ductular proliferation. Parenchymal features of early HCCs are summarized as follows: (1) thin trabecular structure, (2) hypercellularity, (3) hyperstainability of cytoplasm, and (4) microacinar formation. Detailed understanding of the total biopsy procedure and various difficult lesions is necessary for a correct biopsy diagnosis. Evaluation of noncancerous tissue is also required to attain a better understanding of the developmental process and clinical stages of HCCs.

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Overexpression of glutamine synthetase in human primary liver cancer

Cited by 89 publications

References 21 publications

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

Pathologic diagnosis of early hepatocellular carcinoma: A report of the international consensus group for hepatocellular neoplasia

The metabolic organization of the adult human liver: A comparative study of normal, fibrotic, and cirrhotic liver tissue

Histological features of early hepatocellular carcinomas and their developmental process: for daily practical clinical application

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