In this review the main characteristics, i.e., structure, function and gene expression, of the different mucins are discussed. Mucin-type molecules consist of a core protein moiety (apomucin) where a number of carbohydrate chains are attached to serines and threonines by glycosidic bonds. O-linked carbohydrates form up to 80% of the molecule and the length of the glucidic side chains varies from one to more than 20 residues. At least eight mucin-like genes have been isolated so far, and the main characteristic is the presence of a central domain composed of a variable number of "tandem repeats". The sequence homology of the central domain among the different members of the mucin-type family is limited, indicating that this internal domain is unique for each mucin. Thanks to the integrated results of genetic, immunological and biochemical studies, it is now possible to identify eight apomucin genes, namely MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6 and MUC7. MUC1 is the best characterized mucin and it is expressed on the apical surface of most polarized epithelial cells. The MUC1 gene has been cloned and sequenced. The MUC2 gene encodes a typical secretory gel-forming mucin which represents the predominant form in human intestinal and colon tissues. Another intestinal mucin is MUC3. The MUC4, MUC5AC and MUC5B genes have been isolated from a bronchial tissue cDNA library. The MUC4 and MUC5AC genes are mainly expressed in the respiratory tract, in gastric and reproductive mucosa, while MUC5B is highly detectable only in the bronchial glands. The MUC6 gene is expressed by gastric tissue and, recently, MUC7 has been cloned and sequenced using a salivary cDNA library.
One approach in the treatment of ovarian cancer patients involves the infusion of autologous T lymphocytes coupled with a bispecific monoclonal antibody MOv18/anti-CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian carcinomas and the CD3 T cell receptor. However, little is known about the in vivo biodistribution of injected activated lymphocytes, information that could be obtained by scintigraphic imaging of radiolabelled T cells in order to visualize the migratory pattern. We compared the efficiency, stability and toxicity of technetium-99m hexamethylpropylene amine oxime (HMPAO), indium-111 oxine and fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of 111In-oxine and 18F-FDG using 2.5x10(8) lymphocytes (68% and 64%, respectively) were more than twice that of 99mTc-HMPAO (31%). Retention of the radionuclide in the cell was highest in the case of 111In-oxine labelling (less than 25% of the initial cell-bound activity released after 240 min, as compared with 44% of the 99mTc label in the same period and 45% of 18F radionuclide released after 150 min). None of the three radiolabelling reagents induced any significant alteration in cell viability or immunophenotype. However, both 111In-oxine and 18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian carcinoma cell line IGROV1, and all three radiolabelling reagents caused a significant reduction in the proliferative ability of labelled lymphocytes compared to controls, with cell death occurring after 8-9 days. Radiolabelling with the more stable 111In-oxine reagent using a higher number of lymphocytes (1.4x10(9)) but the same total activity (around 55.5 MBq) resulted in improved labelled T cell viability and proliferative ability, although the mean labelling efficiency decreased (35.8%). Together the data suggest that 111In-oxine at low activity per cell is the most appropriate reagent for radiolabelling activated retargeted T lymphocytes useful for in vivo biodistribution studies.
The concept of the immunological surveillance against neoplastic cells was initially proposed by Erlich in 1909 and later elaborated by Burnet. This hypothesis states that the normal function of the immune system, in particular the cell-mediated immunity, is to recognize and destroy the transformed and proliferating tumor cells. The role of cell-mediated immunity during the first steps of tumorigenesis remains controversial. However, there is certain evidence about its importance in the progression and dissemination of cancer. The frequent immunosuppressed condition of cancer patients at tumor relapse or recurrence of secondary tumors is a clinical sign supporting this hypothesis, and many studies have demonstrated a defective immune response in patients diagnosed with advanced cancer. Several mechanisms of escape from the immune surveillance have been described, including the immunoselection of tumor antigen-negative variants, the downregulation of MHC class I expression, suppressive T cells, and the elaboration of immunosuppressive cytokines and other factors. Because of the technical difficulty of isolating the very small amounts from culture supernatants or body fluids, only a few of these substances have been characterized and studied with respect to their biological activity: transforming growth factor-beta (TGF-beta), the protein p15E, interleukin 10 (IL-10), prostaglandin E2 (PGE2), mucins, suppressive E-receptor (SER), immunosuppressive acidic protein (IAP), and adhesion molecules. The possibility of monitoring cancer patients by testing biochemical factors related to cancer growth led to a proposal to measure a number of these factors as tumor markers. Some of them, e.g. mucins, enjoy the consensus of the oncologic community, as for some indications they can help the clinician in the management of cancer patients. Except for the class of mucins, the other above-mentioned immunosuppressive factors have not found any clinical application in the laboratory routine because the information deriving from their measurement, although of speculative and scientific interest, has limited clinical value at present. Nevertheless, even if they have no impact on patient management, these substances do have a potential role to play in the study of cancer patients, and should be taken into account when developing new therapeutic strategies.
Neuron-specific enolase (NSE) may be of interest for the prognostic evaluation and follow-up surveillance in patients with neuroblastoma. We evaluated NSE levels in 80 patients with neuroblastoma. The marker correlated with stage (in stage 1 patients, the median NSE level was 9.9 ng/ml, in stage 2, 45.1 ng/ml, in stage 3, 49 ng/ml, in stage 4, 93.9 ng/ml, in stage 4S, 53.4 ng/ml) and with survival. In patients with a favorable or a poor outcome, the difference in basal NSE serum levels was statistically significant (p = 0.0001). Serial measurements revealed that there was a good correlation between NSE levels and disease course. We concluded that NSE is a good marker for neuroblastoma and its quantitative determination in serum is valuable in the management of these patients to confirm the diagnosis, monitor the effect of treatment and detect recurrent disease.
Neuroendocrine tumors (NETs) are rare neoplasms characterized by a low proliferative index and, in some cases, a favorable prognosis. These tumors often overproduce and release biologically active substances that are responsible for severe syndromes. Tumor marker measurement provides the clinician with useful information for the management of NET patients. The substances released by overproducing tumors are currently used as biomarkers, but there is a need for sensitive markers also for the "biochemically silent" NETs. The most effective and reliable blood marker available today is chromogranin A (CgA). Because of its high sensitivity and specificity, this glycoprotein can be used for the diagnosis, prognosis and followup of NETs. Furthermore, CgA measurement can be used for monitoring those tumors not over-producing or releasing any hormones or biological amines. This paper is a synthetic review on the value of CgA in NET management and reports our experiences with CgA measurement in NET patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.