Tumour-associated antigens and their anti-cancer applications.

So far, a number of tumour-associated antigens (TAAs), such as heat shock proteins, alpha-fetoprotein, carcino-embryonic antigen and others have been identified in a variety of malignant tumours. Differences in the expression levels of TAAs in cancers compared with normal cells have led to these antigens being investigated as diagnostic and prognostic biomarkers or exciting targets in cancer treatment. Here, we systematically list the current representative TAAs to shed some light on current approaches and challenges for their anti-cancer application in cancer therapy. In this review, we discuss the ongoing pre-clinical studies and clinical development of TAAs in human cancers, and the potential application of these TAAs in the diagnosis and prognosis for cancer treatment.

Screening and determinations of tissue polypeptide antigen by label-free optical immunosensing method.

Based on the specificity of the immunoreaction of anti-body and antigen, and the resulting localized surface plasmon resonance extinction response of functionalized nano-Au monolayer on glass chip, a novel label-free optical immunosensor with amplified sensitivity has been developed for the detection of tissue polypeptide antigen (TPA). The nano-Au monolayer on glass chip was controllably prepared using 3-mercaptopropyltrimethoxysilane (MPTMOS) as linker by a solution self-assembly method. To analyze its quality, the nano-Au monolayer was characterized by UV-visible spectrum and atomic force microscopy (AFM). The resulting chip was modified by tissue polypeptide antigen antibody (anti-TPA), and then bovine serum albumin (BSA) was employed to block the possible remaining active sites of the nano-Au monolayer. An immunosensor was constructed with biocompatible monolayer nano-Au membrane and the desirable TPA antibody/BSA composite membrane, and it showed good selectivity, high sensitivity and a wide linear response to TPA in the range of 1-1000 ng L(-1) with a detection limit of 1.2 x 10(-3) ng L(-1), as well as good stability and long-term life. Owing to its ease of operation, low detection limit and low cost, it is expected that the proposed procedure may hold great promise in both research-based and clinical assays.

Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases.

The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean +/- SD) were between 9.3 +/- 4.4 to 13.7 +/- 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti-CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute-phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies.

Association between platelet activation and fibrinolysis in acute stroke patients.

We aimed to evaluate platelet activation and fibrinolyis in acute atherosclerotic ischemic stroke patients to clarify the relationship between them. Plasma P-selectin antigen, tissue plasminogen activator (tPA) antigen and activity, and plasminogen activator inhibitor-1 (PAI-1) activity were determined in 60 acute atherosclerotic stroke patients and matched control subjects. All patients were examined within 72 h after stroke onset. The levels of P-selectin, tPA antigen, and PAI-1 activity were all significantly higher in stroke patients compared with controls (all p < 0.0001); the level of tPA activity was significantly lower in patients than that in controls (p < 0.0001). These markers did not change much at different time points within 72 h. In stroke group, P-selectin concentration was highly correlated to PAI-1 activity (r = 0.8433, p < 0.001), but not to tPA antigen (r = -0.1752, p > 0.05), and tPA activity (r = 0.2465, p>0.05), which was further confirmed in the multiple linear regression analysis (F = 47.052, p < 0.0001). Our results indicate increased platelet activation and decreased fibrinolysis in patients with acute atherosclerotic ischemic stroke. Increased platelet activation may be correlated with decreased fibrinolysis.

Tissue polypeptide-specific antigen (TPS) immunoassay in the diagnosis and clinical staging of prostatic carcinoma. Comparison with prostate-specific antigen (PSA).

UNLABELLED: This experimental study investigated the potential role of Tissue Polypeptide-Specific Antigen (TPS) in comparison with Prostate-Specific Antigen (PSA) in the diagnosis and the clinical and pathological staging of prostate cancer. Serum TPS and PSA levels were determined in 128 patients (pts) with benign prostatic hypertrophy (BPH; Group 1) and in 92 pts with prostate cancer (Group 2). TPS was also measured in a control group of 100 healthy subjects. Normal cutoff values of 85 U/l for TPS and 4 ng/ml for PSA were determined on the basis of ROC curve analysis. The sensitivity, specificity and accuracy in the diagnosis of prostate cancer were 49%, 95% and 76% for TPS, and 84%, 90% and 87% for PSA. The combination of the two markers provided a higher accuracy (88%), improving the sensitivity of PSA, since 47% of patients with normal PSA had pathological levels of TPS. TPS showed an increase in sensitivity from low to higher stages of disease and, in patients with skeletal involvement, from small to larger numbers of bone metastases (Kruskal Wallis p < 0.0001). Nevertheless, TPS serum levels are not useful in the clinical staging of prostate cancer as they have a poorer performance than PSA. TPS was ineffective (ROC curve area = 0.68) in predicting extraprostatic disease and demonstrated a reduced ability (area = 0.78) to identify skeletal involvement. Moreover, the combination of the two markers did not significantly improve the performance of PSA alone. The serum concentration of TPS in patients with localized tumors was not related to the degree of tumor cell differentiation evaluated by the Gleason score. CONCLUSION: Our preliminary experience suggests that TPS in association with PSA may be useful at the time of diagnosis of prostate cancer. However, these preliminary data have to be confirmed by larger clinical trials and the role of this association in the clinical setting needs to be analyzed with an adequate evaluation of the cost-effectiveness ratio.

[The diagnostic value of determination of tissue polypeptide specific antigen (TPS) in serum of women with breast cancer]. / Wartosc diagnostyczna oznaczania specyficznego polipeptydowego antygenu tkankowego (TPS) w surowicy kobiet z nowotworem gruczolu sutkowego.

Studies were conducted in serum of 132 women. In 39 cases mastopathia fibrosocystica was diagnosed whereas the remaining 73 women had malignant breast cancer: 34-lobulare, 20-ductale and 19 of them-ductale and lobulare carcinoma. The concentration of tissue polypeptide specific antigen was determined by immunoenzymatic, BEKI DIAGNOSTIC test. The results showed, that TPS antigen concentration in serum of women without cancer symptoms was physiological, under 80 U/l. Whereas in 42 patients with benign neoplasm, in 5 of them the concentration of determined marker was over the cut-off. Our study showed, that the mediane of concentration of TPS antigen in serum of women with malignant neoplasm was over twice higher than in healthy women. The frequency of increased results and absolute value of TPS level showed trend to significant increase with the clinical progression of disease and grade of histological malignancy of neoplasm. The similar dependence of TPS concentration on metastasis number to lymph nodes was observed.