Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of CA125, CA19.9, CA15.3 CA72.4, and TATI were serially measured during and after chemotherapy in 43 patients with epithelial ovarian cancer having elevated concentrations of one or more of the antigens before initial surgery. The value of 35 U/ml was chosen as cutoff level of CA125 for the monitoring of disease. Changes in the serum levels of CA125, CA19.9, CA15.3, CA72.4, and TATI correlated with the clinical course of disease in 87.4% of 215, 76.3% of 80, 71.3% of 122, 76.0% of 167, and 48.5% of 101 instances, respectively. After the sixth course of monthly primary chemotherapy, elevated antigen levels were strong predictors of persistent disease, while normal antigen values were associated with both positive and negative second-look findings. It is worth noting that antigen levels above the cut-off limits before the third course, but still in the normal range after the sixth course, seemed to be predictive of positive second-look findings. Among patients with elevated antigen levels at diagnosis, clinical detection of neoplastic progression after treatment was stopped was preceded by an elevation of serum CA125 in 93.3% of 15 patients, of serum CA19.9 in 80.0% of 5 patients, of serum CA15.3 in 66.7% of 9 patients, of serum CA72.4 in 81.8% of 11 patients, and of serum TATI in 40% of 10 patients. In patients with positive CA125 assay at diagnosis, the concomitant evaluation of the other antigens did not seem to be of additional benefit for monitoring epithelial ovarian cancer. However, the measurement of the other tumor markers could represent an interesting biochemical tool for the management of patients with negative CA125 assay. In particular the evaluation of serum CA19.9 or CA72.4 could be very useful in the monitoring of patients with mucinous ovarian cancer, which often fails to express CA125 antigen.
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PMID:The concomitant determination of different serum tumor markers in epithelial ovarian cancer: relevance for monitoring the response to chemotherapy and follow-up of patients. 154 92

Twenty four patients with epithelial ovarian cancer, who were treated by chemotherapy after debulking surgery, were monitored by serial monthly CA125 estimation and half-yearly computerized axial tomogram (CAT) of abdomen and pelvis. The efficiency of these monitoring methods and that of clinical examination were compared. The use of CA125 alone was superior to the use of clinical assessment alone in the detection of tumor progression (p less than 0.01). The addition of the expensive routine half-yearly CAT examination did not improve the tumor detection rate (p less than 0.05). Hence, CAT examination should not be used routinely to detect recurrence of tumor in patients without a raised CA125 level. However, in patients with increased CA125 level, CAT examination had a place in locating and in determining the extent of the tumor which in selected patients may enable us to make changes in therapy without laparotomy and in other patients may help us to make a better assessment on whether further debulking is possible.
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PMID:Role of CA125 and abdominal pelvic computerized axial tomogram in the monitoring of chemotherapy treatment of ovarian cancer. 226 70

Preoperative serum neopterin, soluble interleukin-2 receptor (sIL-2R), and CA125 levels were assayed in 47 patients with ovarian cancer and 113 patients with benign ovarian disease undergoing laparotomy. The cutoff limits of the antigens for the preoperative evaluation of ovarian cancer were fixed according to the Youden plot, using the patients with benign ovarian disease as controls. These limits were 7.9 nmole/liter for neopterin, 71 U/ml for sIL-2R, and 83 U/ml for CA125. The preoperative mean values of serum neopterin and sIL-2R were significantly higher in patients with ovarian cancer than in those with benign ovarian disease. Therefore these tests would seem to be useful in distinguishing benign from malignant ovarian masses. Serum levels of neopterin, sIL-2R, and CA125 above the cutoff limits were detected in 66.0, 78.7, and 76.6% of patients with ovarian cancer. Patients with advanced-stage disease (FIGO > or = III) were significantly more likely to have a higher percentage of elevated values of sIL-2R and CA125, but not neopterin, compared to patients with early-stage disease. However, neopterin was the antigen most often raised in early disease. As for advanced ovarian cancer, preoperative serum sIL-2R levels were higher in patients who developed progressive disease than in those who were progression-free (P = 0.02) after a median follow-up time of 18 months. Furthermore, a trend to higher preoperative serum neopterin values was found in the former patients (P = 0.08). Tumor progression occurred in 3 of 8 (37.5%) patients with low serum preoperative neopterin (< 7.9 nmole/liter) and in 16 of 19 (84.2%) patients with elevated serum neopterin, respectively (P = 0.027). Multivariate analysis on a larger number of patients followed for a longer time is warranted to elucidate the prognostic relevance of these immunologic markers in ovarian cancer. Changes in serum neopterin, sIL-2R, and CA125 levels correlated with the disease course in 50.0, 54.8, and 92.9% of 42 instances, respectively. Moreover, serum CA125 was more sensitive than the other two antigens in the early detection of tumor progression. Therefore serial neopterin and sIL-2R measurements seem to be of limited value in monitoring the disease course in patients with ovarian cancer.
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PMID:Elevated serum levels of neopterin and soluble interleukin-2 receptor in patients with ovarian cancer. 815 96

The longitudinal follow-up of a patient with an advanced adenocarcinoma of the ovary sheds new light on the involvement of the pineal in carcinogenesis. The changes in the circadian MESOR of 6-sulfoxy-melatonin following a course of chemotherapy may differ in relation to the success or failure of treatment, yet the MESOR does not correlate with tumor burden assessed by circulating CA125. By contrast, the ratio of circaseptan-to-circadian amplitudes involving two chronome components correlates with the cancer marker. To that extent, the study reveals a critical about 7-day (circaseptan) aspect of the pineal involvement in cancer progression. This information could be exploited in designing schedules of melatonin administration to cancer patients.
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PMID:Chronome of urinary 6-sulfoxy-melatonin excretion, circulating CA125, cancer progression and therapeutic response. 855 37

This combined analysis investigated the effect of marimastat, a specific inhibitor of matrix metalloproteinases, on markers of tumor progression measured in patients with advanced cancer. By defining the tolerability and biological activity of the drug, it aimed to establish an appropriate dose range for use in Phase III trials. Patients with advanced, serologically progressive ovarian, prostatic, pancreatic, and colorectal cancer were recruited into six nonrandomized, dose ranging, multicenter clinical trials in North America and Europe. The biological activity of marimastat was assessed by serial measurements of the serum tumor markers carcinoembryonic antigen, CA125, CA19-9, and prostate-specific antigen. Patients were recruited with tumor markers rising by more than 25% averaged over a 4-week screening period. A biological effect was defined as a level of tumor marker at the end of treatment no greater than at study entry; a partial biological effect was defined as a rise in the level of tumor marker over the treatment period of 0-25% per 4 weeks. Pharmacokinetic and safety data were collected and assessed as the studies progressed. All patients were followed up for survival.
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PMID:Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies. 960 66

Ovarian carcinomas are thought to arise in the ovarian surface epithelium (OSE). Although this tissue forms a simple epithelial covering on the ovarian surface, OSE cells exhibit some mesenchymal characteristics and contain little or no E-cadherin. However, E-cadherin is present in metaplastic OSE cells that resemble the more complex epithelia of the oviduct, endometrium and endocervix, and in primary epithelial ovarian carcinomas. To determine whether E-cadherin was a cause or consequence of OSE metaplasia, we expressed this cell-adhesion molecule in simian virus 40-immortalized OSE cells. In these cells the exogenous E-cadherin, all three catenins, and F-actin localized at sites of cell-cell contact, indicating the formation of functional adherens junctions. Unlike the parent OSE cell line, which had undergone a typical mesenchymal transformation in culture, E-cadherin-expressing cells contained cytokeratins and the tight-junction protein occludin. They also formed cobblestone monolayers in two-dimensional culture and simple epithelia in three-dimensional culture that produced CA125 and shed it into the culture medium. CA125 is a normal epithelial-differentiation product of the oviduct, endometrium, and endocervix, but not of normal OSE. It is also a tumor antigen that is produced by ovarian neoplasms and by metaplastic OSE. Thus, E-cadherin restored some normal characteristics of OSE, such as keratin, and it also induced epithelial-differentiation markers associated with weakly preneoplastic, metaplastic OSE and OSE-derived primary carcinomas. The results suggest an unexpected role for E-cadherin in ovarian neoplastic progression.
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PMID:E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. 1033 73

Epithelial ovarian carcinomas are thought to originate in the ovarian surface epithelium (OSE), i.e., the mesothelium covering the ovary, but experimental evidence for this origin has been lacking. Contrary to most epithelia, where neoplastic progression is associated with a reduction of E-cadherin, this cell-cell adhesion molecule is sparse in normal human OSE but its expression increases with the development of ovarian epithelial metaplasia and neoplasia. Concurrently, the tumors tend to acquire characteristics of the complex epithelia of the oviduct and uterus. The high proportion of ovarian cancers where such aberrant Mullerian differentiation occurs suggests that this change may confer a selective advantage on the transforming cells. We previously demonstrated that increased E-cadherin expression may be a cause, rather than a consequence, of such Mullerian differentiation. E-cadherin was transfected into SV40 large T antigen-immortalized, E-cadherin-negative cells derived from normal OSE. Constitutive expression of E-cadherin re-established normal epithelial markers that had been lost in culture, such as keratin, and induced markers of metaplasia and neoplasia, such as CA125. In the present study, SV40-immortalized, E-cadherin-transfected cells, but not the E-cadherin-negative controls, were found to be anchorage-independent and to form transplantable, invasive s.c. and i.p. adenocarcinomas in 100% of injected SCID mice. Tumor cells injected i.p. seeded the mesenteries and omentum, invaded the liver and thigh musculature and produced ascites. The presence of SV40 large T antigen in the tumor cell nuclei confirmed their origin as transfected OSE cells. Our results demonstrate that ovarian adenocarcinomas can be derived by genetic manipulation of normal human OSE.
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PMID:An ovarian adenocarcinoma line derived from SV40/E-cadherin-transfected normal human ovarian surface epithelium. 1065 37

Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a highly specific enzyme whose only known substrate is the GPI anchor of cell surface proteins. GPI-PLD measurements, however, are technically difficult since the enzyme is expressed at low levels in cells and tissues, and serum contains large amounts of inactive, latent GPI-PLD interfering with protein-based assays. We have therefore developed a semi-quantitative RT-PCR method to measure mRNA expression of all known GPI-PLD isoforms in cells and tissues. In human ovarian cancer cell lines, GPI-PLD mRNA expression correlated with GPI-PLD enzyme activity and with the shedding of the GPI-anchored tumor and prognostic markers, urokinase receptor and CA125, from the cell surface. This supports a potential role for this enzyme in the generation of circulating prognostic markers in malignant tumors. Similarly, in human epithelial cells of the skin, GPI-PLD mRNA expression increased with tumor progression. Whereas normal keratinocytes did not express significant amounts of GPI-PLD mRNA, expression was dramatically induced by serum in immortalized HaCaT keratinocytes and constitutively high and independent of serum in tumorigenic A431 epidermoid carcinoma cells. In addition, GPI-PLD expression was significantly increased in highly malignant. H-ras-transfected murine bladder carcinoma cells as compared to the low malignant, non-transfected parental cells. The competitive RT-PCR described here represents the first quantitative assay specific for cellular GPI-PLD isoforms, and our in vitro analyses suggest that GPI-PLD expression might be associated with tumor malignancy.
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PMID:GPI-specific phospholipase D mRNA expression in tumor cells of different malignancy. 1209 Apr 69

CA125 is an ovarian cancer antigen whose recently elucidated primary structure suggests that CA125 is a giant mucin-like glycoprotein present on the cell surface of tumor cells. Here, we establish a functional link between CA125 and beta-galactoside-binding, cell-surface lectins, which are components of the extracellular matrix implicated in the regulation of cell adhesion, apoptosis, cell proliferation and tumor progression. On the basis of mass spectrometry and immunological analyses, we find that CA125 is a counter receptor for galectin-1, as both soluble and membrane-associated fragments of CA125 derived from HeLa cell lysates are shown to bind specifically to human galectin-1 with high efficiency. This interaction is demonstrated (1) to depend on beta-galactose-terminated, O-linked oligosaccharide chains of CA125, (2) to be preferential for galectin-1 versus galectin-3 and (3) to be regulated by the cellular background in which CA125 is expressed. Despite lacking a conventional signal peptide, a CA125 C-terminal fragment of 1148 amino acids, representing less than 10% of the full-length protein, retains the ability to integrate into secretory membranes such as the endoplasmic reticulum (ER) and the Golgi, and is targeted to the plasma membrane by conventional secretory transport. As demonstrated by a novel assay that reconstitutes non-conventional secretion of galectin-1 based on fluorescence-activated cell sorting (FACS), we find that tumor-derived HeLa cells expressing endogenous CA125 present more than ten times as much galectin-1 on their surface compared with non-tumor-derived, CA125-deficient CHO cells. Intriguingly, both the galectin-1 expression level and the cell-surface binding capacity for galectin-1 are shown to be similar in CHO and HeLa cells, suggesting that CA125 might be a factor involved in the regulation of galectin-1 export to the cell surface.
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PMID:The cancer antigen CA125 represents a novel counter receptor for galectin-1. 1261 72

CA125 is a mucin commonly employed as a diagnostic marker for epithelial ovarian cancer. Induction of humoral responses to CA125 leads to increased survival times in patients with this form of cancer, suggesting a potential role for this mucin in tumor progression. In this study, oligosaccharides linked to CA125 derived from the human ovarian tumor cell line OVCAR-3 were subjected to rigorous biophysical analysis. Sequencing of the O-glycans indicates the presence of both core type 1 and type 2 glycans. An unusual feature is the expression of branched core 1 antennae in the core type 2 glycans. CA125 is also N-glycosylated, expressing primarily high mannose and complex bisecting type N-linked glycans. High mannose type glycans include Man5-Man9GlcNAc2. The predominant N-glycans are the biantennary, triantennary, and tetraantennary bisecting type oligosaccharides. Remarkably, the N-glycosylation profiles of CA125 and the envelope glycoprotein gp120 (derived from H9 lymphoblastoid cells chronically infected with HIV-1) are very similar. The CA125-associated N-glycans have also recently been implicated in crucial recognition events involved in both the innate and adaptive arms of the cell-mediated immune response. CA125 may therefore induce specific immunomodulatory effects by employing its carbohydrate sequences as functional groups, thereby promoting tumor progression. Immunotherapy directed against CA125 may attenuate these immunosuppressive effects, leading to the prolonged survival of patients with this extremely serious form of cancer.
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PMID:Characterization of the oligosaccharides associated with the human ovarian tumor marker CA125. 1273


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