Tumor-associated Trypsin Inhibitor Concentrations Research Articles

Tumor-associated trypsin inhibitor in patients with endometrial cancer.

The aim of the study was to look for prognostic factors of metastasis or recurrence in patients with endometrial cancer. Tumor-associated trypsin inhibitor (TATI) concentrations were measured in serum of 317 patients with endometrial cancer. The assay was done 7 times in each patient, from the moment of diagnosis until the start of follow-up after the completion of treatment. Observation of patients after treatment lasted from 0 to 16 years. The TATI levels in patients with adverse prognostic factors accumulated in the first 3 assays and then decreased to zero. Mean TATI concentrations were significantly higher in patients with clinically advanced disease (stage IIIB) than patients at stage I (Kruskal-Wallis p = 0.0446). An increase in the concentration by more than 10.6% in the first 3 assays was significantly correlated with disease relapse (Mann-Whitney Z = -6.06653, p = 0.00000) and local or distant recurrence (Mann-Whitney Z = -4.97475, p = 0.000001). A significant increase in the TATI level in the first 3 tests also occurred in patients who died during the study period (Kruskal Wallis p<0.001). In our series of patients with endometrial cancer, TATI proved to be a sensitive indicator of disease recurrence and distant metastasis, with a sensitivity of 84.4% and 75.7%, respectively. TATI seems to behave as a prognostic factor in certain subgroups of patients with endometrial cancer.

Prognostic significance of tumor-associated trypsin inhibitor (TATI) and human chorionic gonadotropin-β (hCGβ) in patients with hepatocellular carcinoma

Aim. Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer death worldwide. The aim of this study was to evaluate the prognostic value of serum tumor-associated trypsin inhibitor (TATI) and the free β subunit of human chorionic gonadotropin (hCGβ) in patients with HCC. Methods. The serum concentrations of TATI and hCGβ were determined by time-resolved immunofluorometric assays (IFMA) in pretreatment serum samples from 144 patients with HCC. Clinical data were retrieved from patient records and survival data obtained from Statistics Finland. Results. The overall cumulative disease-specific survival was 69% at 1 year, 50% at 2 years and 33% at 5 years. Disease-specific median survival time was 26 months. The overall survival in patients with low serum concentrations of TATI or hCGβ was statistically significantly better than in patients with elevated concentrations (p = 0.003 and 0.003, respectively). In multivariate analysis, both serum TATI and serum hCGβ were independent prognostic markers. Conclusion. The results imply that elevated serum concentrations of TATI and hCGβ are predictors of adverse prognosis in patients with HCC and appear to be useful adjuncts in predicting prognosis in patients with HCC.

Validation and comparison of tumor-associated trypsin inhibitor (TATI) immunoassays

BackgroundTumor-associated trypsin inhibitor (TATI) is mainly proposed as a tumor marker for ovarian cancer. However, recent discoveries of TATI in cancer and inflammatory diseases show that assay of TATI in biological samples is of increasing interest. MethodsWe validated a previously described TR-IFMA and a newly developed dual-monoclonal sandwich ELISA for TATI. These methods were compared with a commercial radioimmunoassay (RIA). We studied preanalytical factors affecting serum TATI concentrations and established age- and gender specific reference intervals using serum samples from 195 healthy volunteers. ResultsThe assay range and precision were 0.8–45μg/L and <9.1% for the ELISA, and 0.13μg/L–150μg/L and <12.5% for the TR-IFMA, respectively. Both assays correlated well with a RIA. Type of blood sample and nutritional status were not critical and TATI was stable in serum samples when stored at +4°C and −20°C for 4weeks and at −80°C for 8weeks. The 95% reference limits for serum TATI in adults were 5.2–15.3μg/L in the age group 18–70years and 7.5–21.3μg/L in the age group >70years. ConclusionsSignificantly higher concentrations of serum TATI were observed in elderly women and in men. Both ELISA and TR-IFMA technologies can be employed to develop sensitive and robust immunoassays for TATI using monoclonal antibodies.

Pulmonary trypsin-2 in the development of bronchopulmonary dysplasia in preterm infants.

In the preterm infant, lung injury can lead to irreversible tissue destruction and abnormal lung development. We examined whether pulmonary trypsin, a potent matrix-degrading serine proteinase and proteinase-cascade activator, is associated with the development of bronchopulmonary dysplasia (BPD) in preterm infants. Samples of tracheal aspirate fluid were collected from 32 intubated preterm infants during their first 2 postnatal weeks. The presence and molecular forms of trypsin in tracheal aspirate fluid samples were analyzed by zymography and Western blotting. The concentrations of trypsinogen-1 and -2 and tumor-associated trypsin inhibitor were measured by immunofluorometry. For examining the expression of trypsin-2 in lung tissue, immunohistochemistry was performed on autopsy specimens of fetuses, of preterm infants who died from respiratory distress syndrome or BPD, and of term infants without lung injury. In infants who subsequently developed BPD (n = 18), we detected significantly higher concentrations of trypsinogen-2 during postnatal days 5 to 10 compared with those who survived without it. There was no difference in trypsinogen-1 concentrations. Tumor-associated trypsin inhibitor concentrations were significantly lower in infants who needed mechanical ventilation for >1 week. Immunohistochemistry demonstrated that trypsin-2 was predominantly expressed in bronchial and bronchiolar epithelium. In 2 preterm infants who died from prolonged respiratory distress syndrome, trypsin-2 was also expressed in vascular endothelium. The levels of trypsinogen-2 are higher during postnatal days 5 to 10 in infants who subsequently develop BPD. The results suggest that high levels of pulmonary trypsin-2 may be associated with the development of BPD. This raises the possibility that therapy with exogenous proteinase inhibitors might prevent the development of BPD in preterm infants with respiratory distress.

Elevated Serum Inhibin and Tumor-Associated Trypsin Inhibitor Concentrations in a Young Woman with Dysgerminoma of the Ovary

We describe a patient with dysgerminoma who had elevated serum inhibin, tumor-associated trypsin inhibitor (TATI), and CA 125 concentrations, which increased progressively during follow-up of the advancing disease. Inhibin levels correlated closely with disease behavior. In contrast to inhibin, serum TATI and CA 125 failed to reveal the presence of silent disease.

Serum Carcinoembryonic Antigen, Cancer Antigen 125, Cancer Antigen 15-3, Squamous Cell Carcinoma, and Tumor-associated Trypsin Inhibitor Concentrations during Healthy Pregnancy

In the management of cancer patients, tumor-associated antigens are measured in serum as noninvasive tests for relapse detection [reviewed in Ref. (1) ]. The tests have limited specificity because the serum concentrations of the antigens can be affected by pathophysiological conditions such as renal insufficiency, hepatic diseases, and inflammation (2) . The temporal changes of tumor markers during pregnancy are not well documented. Although some have reported values grouped by trimester of pregnancy (3) , longitudinal studies are rare. We have studied the tumor markers CEA (carcinoembryonic antigen), CA (cancer antigen) 125, CA 15-3, SCC (squamous cell carcinoma), and TATI (tumor-associated trypsin inhibitor), which are widely used in gynecological tumors. CEA is expressed in many malignancies and is useful for the monitoring of colon, lung, and breast cancers (4) . CA 125 and CA 15-3 belong to the family of carbohydrate antigens also named mucins (1) . CA 125, which was identified by a monoclonal antibody raised to an ovarian carcinoma cell line (OC125), is used for the follow-up of nonmucinous ovarian cancer (1) . It displays increased seric concentrations in cases of serous effusions (2) . CA 15-3, which was identified by two monoclonal antibodies 115D8 and DF3, is the most widely used tumor marker for breast carcinoma (4) . SCC (or Ta-4) is a tumor-associated antigen isolated from squamous cell carcinoma of uterine cervix (5) and is used for the follow-up of epidermoid tumors (cervical uterine carcinoma or epidermoid lung cancer) (6) . TATI was isolated from the urine of an ovarian cancer patient (7) . It is used for the follow-up of mucinous ovarian cancer (8) and other malignancies including cancers from the urogenital …

Tumor-Associated Trypsin Inhibitor (Tati) in Pleural Effusions

The purpose of this study was to evaluate the usefulness of tumor-associated trypsin inhibitor (TATI) determination in serum and pleural fluid for differential diagnosis of relapsing pleural effusions. The concentrations of TATI were determined in samples of serum and pleural fluid from 51 patients with pleural effusions comprising 20 benign exudates, 5 transudates and 26 malignant effusions. TATI levels overlapped in benign and malignant fluids. This precludes the use of this marker for diagnosis of pleural effusions. For this purpose CEA seems to be the best tumor marker with a sensitivity frequently higher than that of cytology.

Tumor-Associated Trypsin Inhibitor as a Possible Marker in Male Infertility

The concentrations of tumor-associated trypsin inhibitor (TATI) in the seminal plasma of infertile males was studied. The TATI levels in seminal plasma were not correlated with either sperm count or ejaculate volume. High levels were observed in some men with unexplained infertility and high or normal sperm counts, whereas normal levels were observed in males with antisperm antibodies. The concentrations in seminal plasma were stable in the same subjects. These results suggest that TATI may be an important marker of reproductive pathology in men.

Tumor-Associated Trypsin Inhibitor (Tati) in Patients with Colorectal Carcinoma. A Critical Comparison with Cea

We have evaluated the clinical utility of tumor-associated trypsin inhibitor (TATI) in colorectal cancer and compared it with carcinoembryonic antigen (CEA), the classical marker for this disease. We measured the serum levels of these markers in 53 patients with colorectal carcinoma before and after surgery. CEA was found to have greater sensitivity than TATI in this disease. The TATI concentrations did not correlate as well as CEA with the presence or absence of metastasis and with the course of the disease after surgery. The use of TATI together with CEA for detection or follow up of colorectal cancer does not seem to be useful because a significant increase of positivity is not obtained as compared with determination of CEA alone.

Tumor-Associated Trypsin Inhibitor in Induced and Acquired Immunodeficiency. Studies on Transplanted and Hiv-Infected Patients

A new tumor marker, tumor-associated trypsin inhibitor (TATI), was studied in 5 patients who received successful kidney or pancreas grafts and in 30 subjects with antibodies against human immunodeficiency virus. Serum TATI concentrations were very high during the four first days after transplantation. Thereafter the serum levels decreased when the peptide was eliminated through the kidney. Consequently, the urine values were very high. The TATI concentrations of HIV positive subjects were compared with serum levels of HIV antigen and antibody, by Western blotting and determination of peripheral T-lymphocyte subpopulations. The occurrence of high concentrations of TATI in some HIV positive subjects and especially in AIDS patients, suggests that TATI could be useful in exploring physiopathological aspects of severe immunodeficiencies even if TATI levels were not correlated with the commonly used markers of the immune system status. The increased levels of TATI in immunological disorders suggests its possible use in assessing the immune response against cancer.

Serum Tati Levels and Clinical Correlation in Tumors of the Head and Neck

By radioimmunoassay (RIA) we studied tumor-associated trypsin inhibitor (TATI) in 152 serum samples, divided into three groups: 35 healthy subjects, used as controls; 25 individuals with benign pathology of the ear, nose and throat (ENT) region; 92 serial samples obtained from 69 patients with malignant disease of the head and neck. The malignant ENT group were classified in four stages according to the degree of tumor activity. The TATI concentrations (mean +/- SD) were as follows: control group, 16.0 +/- 3.4; benign group, 17.1 +/- 6.7; A0, 14.8 +/- 11.5; A1, 12.1 +/- 3.5; A2, 17.01 +/- 1.4; A3, 43.0 +/- 54.9.

Tumor-Associated Trypsin Inhibitor (Tati) in the Diagnosis of Lung Cancer

To evaluate the usefulness of tumor-associated trypsin inhibitor (TATI) as a marker for the diagnosis of lung cancer we determined serum levels of this peptide in 255 patients with lung cancer and in 74 patients with chronic obstructive lung disease. A reference population consisting of 151 healthy volunteers was also studied. TATI concentrations were measured by radioimmunoassay. As a cut-off point we used the 99th percentile of the TATI concentrations in a reference population, which was 32 micrograms/l. TATI does not appear to be a good tumor marker in lung cancer. Its sensitivity is poor in comparison with CEA and TPA. The correlation between TATI levels and stage of the disease and histological type was weak.

Tumor-Associated Trypsin Inhibitor (Tati) in Benign and Malignant Gastric Disease

We have evaluated the clinical utility of tumor-associated trypsin inhibitor (TATI) as a marker for gastric cancer. For comparison we also studied CEA, CA19-9, CA-50 and TPA. The study comprised 93 patients with cancer and 45 with gastroduodenal ulcers. In 95% of the patients with benign disease the serum TATI concentrations were below 30 micrograms/l. Using this concentration as cut-off level 46% of the cancer patients had elevated levels. These were most common in advanced disease (68% in stage IVB) and patients with anaplastic tumors. Therefore TATI was a useful complement to CEA, which was most often elevated in patients with differentiated tumors. Addition of TATI to the battery of other markers increased the overall sensitivity for cancer from 69% to 80%.

Effect of intracavitary radiotherapy on tumor-associated trypsin inhibitor (TATI) in patients with cervical and endometrial cancer

Tumor-associated trypsin inhibitor (TATI) is a fairly specific serum marker for mucinous ovarian cancer. Very high levels occur in mucinous ovarian cyst fluid, indicating that the elevated levels of TATI in serum are derived from the tumor. However, elevated levels of TATI may also occur in inflammatory disease and after major surgery, suggesting that TATI may also behave as an acute-phase reactant. To further elucidate these questions we have measured the concentration of TATI in urine before and after intracavitary radiotherapy in 13 patients with cervical cancer and 29 patients with endometrial cancer. In 11 patients the concentrations of serum TATI and C-reactive protein (CRP) were also measured. The treatment caused a moderate but significant elevation in the urinary concentration of TATI but affected the serum levels of TATI and CRP only occasionally. The apparent discrepancy between the changes in serum and urine levels of TATI may be explained by the very short (6 min) half-life of TATI in serum. Our results indicate that the mechanisms causing elevation of TATI in urine and of CRP in serum are different. TATI appears to react more rapidly to radiation-induced tissue destruction, whereas CRP is a much more sensitive indicator of bacterial infections.

Concentrations of tumor-associated trypsin inhibitor and C-reactive protein in serum in acute pelvic inflammatory disease.

We measured tumor-associated trypsin inhibitor (TATI) and C-reactive protein (CRP) in serum of 29 patients with proven pelvic inflammatory disease (PID). TATI values were increased in seven (24%), paralleling increases in CRP. TATI was increased by about 3.5-fold in seven of eight patients with CRP concentrations greater than 90 mg/L, but in none of 21 patients with CRP concentrations less than 90 mg/L. TATI concentration and severity of PID as determined by laparoscopy or endometrial biopsy were not correlated. These results suggest that, in severe infections, regulation of TATI synthesis resembles that of acute-phase proteins.

High concentrations of tumor-associated trypsin inhibitor in hemodialyzed patients.

Journal Article High concentrations of tumor-associated trypsin inhibitor in hemodialyzed patients. Get access G Banfi, G Banfi Laboratorio Analisi, Istituto Scientifico S. Raffaele, Milano, Italy Search for other works by this author on: Oxford Academic Google Scholar M Murone, M Murone Laboratorio Analisi, Istituto Scientifico S. Raffaele, Milano, Italy Search for other works by this author on: Oxford Academic Google Scholar G Slaviero G Slaviero Laboratorio Analisi, Istituto Scientifico S. Raffaele, Milano, Italy Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 34, Issue 1, 1 January 1988, Pages 174–175, https://doi.org/10.1093/clinchem/34.1.174a Published: 01 January 1988