Conformational changes in inter-α-trypsin inhibitor heavy chain 4 activate its tumor-specific activity in mice with B16 melanoma.

It is known that blood serum proteins of tumor‑bearing mice display tumor‑specific activity. However, to date, the nature of this activity has remained elusive, and no tumor‑specific proteins have been detected in the blood serum of tumor‑bearing animals compared with those in healthy animals. The present study postulated and investigated the hypothesis that the observed tumor‑specific activity of the blood serum proteins is not associated with the appearance of novel serum proteins but with changes in the conformation of the existing ones.

Identification of serpin (alpha-1-antitrypsin) as serum growth inhibitory factor in murine ehrlich carcinoma by proteomics.

It is well established that serum factors play a role in relapse of tumor diseases after removal of the primary tumor. The molecular nature of these factors and their mechanism of action remain unknown. We focused on host-related mechanisms to identify tumor-specific serum factors of mice bearing Ehrlich carcinoma, which have the potential to confer resistance towards tumor development.

Mononuclear leukocytes from mice with resected tumor induce resistance to transplantation of tumor cells to animals.

Experiments on male C57Bl/6 mice with intraperitoneally transplanted Ehrlich carcinoma and DBA/2 mice with subcutaneously transplanted S-91 melanoma showed that preliminary injection of mononuclear leukocytes obtained from animals 6-8 h after tumor resection induce resistance to transplantation of malignant transformed cells. Our results suggest that not only humoral factors, but also immunocompetent cells are involved in the regulation of tumor growth. The resistance to tumor transplantation was not induced by mononuclear leukocytes isolated over the first hours and 10-12 h after removal of the primary tumor node, which excludes the direct cytotoxic effect of these cells and suggests that this phenomenon is not associated with activation of the effector mechanisms for innate and adoptive immunity.

Evaluation of immunotherapy efficiency in mouse CaO-1 ovarian carcinoma treated by vaccines based on dendritic cells.

Injection of dendritic cells, pulsated by tumor lysate or mucin, containing CA 125 antigen, led to a more than 50% inhibition of tumor growth in female CBA mice with transplanted mouse pseudomucinous CaO-1 ovarian carcinoma in comparison with the control. Tumor-associated CA 125 antigen can be used for obtaining dendritic cell vaccines against ovarian malignant tumors. This trend will extend the potentialities of application of antitumor vaccines based on dendritic cells, as clinical use of this technology is limited by the need in patient's tumor material.

Induction of resistance to murine tumor development is associated with alterations in the glycosylation of blood serum proteins.

The phenomenon of accelerated metastatic tumor growth following the removal of the primary tumor is a major reason for cancer relapse, caused by underlying mechanisms that are not as yet understood. We hypothesized that a growth-stimulating factor is produced by the tumor-bearing host. This assumption was confirmed by an experiment involving the removal of a primary tumor (ascitic and solid Ehrlich carcinoma cells) from C57B1/6 mice, after which accelerated proliferation was observed in the remaining tumor cells.

Specificity of relapses and metastases of experimental transplanted Ehrlich carcinoma and B16 melanoma.

Experiments on female (CBAxC57Bl/6)F1 mice with simultaneously transplanted Ehrlich carcinoma and B16 melanoma showed that removal of one of the primary nodes led to metastasizing of the removed tumor alone. It seems that this specificity of the inhibitory effect of the primary tumor can be explained by peculiarities of glycosylation and subsequent complex formation of serum proteins with the tumor.

Biological activity of hemoglobin-containing complex isolated from blood serum of mice with Ehrlich carcinoma.

Injection of hemoglobin-containing complex of serum proteins isolated from animals with Ehrlich carcinoma led to regression of intraperitoneally and intramuscularly transplanted Ehrlich carcinoma in male C57Bl/6 mice. The hemoglobin-containing complex of serum proteins disturbed cycle distribution of Ehrlich carcinoma cells and caused apoptosis of about 34.3% tumor cells.

Peculiarities of hemoglobin interaction with serum proteins of mice with Ehrlich carcinoma.

In male C57Bl/6 mice with transplanted Ehrlich carcinoma, hemoglobin forms a complex with serum proteins characterized by a molecular weight of about 300 kDa. The complex incorporates proteins weighing 100, 68, 65, and 15 kDa identified by MALDI-TOF mass spectrometry as haptoglobin, serum albumin, gi/26341396 nameless protein Mus musculus, and alpha-hemoglobin, respectively. This complex can possess biological activity and contribute to the control of tumor growth.

Lectin binding to mouse blood lymphocytes during tumor growth.

Binding of FITC-labeled lectins to lymphocytes from intact mice and mice with transplanted Ehrlich carcinoma and CaO-1 ovarian carcinoma was studied by flow cytofluorometry. Specific binding of lectins by mannose and N-acetylgalactosamine was demonstrated. Lectin binding to lymphocytes from animals with tumors decreased by more than 50% in comparison with intact animals.

Tumor-specific changes in mouse serum during Ehrlich carcinoma growth.

Using the method of flow cytofluorometry we found that proteinase activity eliminating antigenic determinants from the surface of tumor cells disappeared from the serum of mice with Ehrlich carcinoma. This activity towards Ehrlich carcinoma cells is present in the sera of mice without tumors and in mice with other transplanted tumors. The serum from mice of one strain with Ehrlich carcinoma showed no protease activity against Ehrlich carcinoma cells in mice of other strain.

Partial elimination of lymphocytes in mice with Ehrlich carcinoma.

Elimination of about 30% lymphocyte population was observed in female Balb/c mice on day 11 after transplantation of Ehrlich carcinoma in comparison with animals without tumor. It was hypothesized that the eliminated population can block the tumor growth. Studies of the temporal and quantitative parameters of lymphocyte elimination with consideration for tumor size are considered to be perspective.

Immunotoxicological characteristics of preparations based on carcinoembryonic antigen and mucin containing CA 125 antigen.

Experiments on male hybrid mice demonstrated that specific immunotherapy with preparations based on carcinoembryonal antigen and mucin containing CA 125 antigen was not associated with general toxicity, local irritating effect, and hepatorenal dysfunction. The absence of toxicity is apparently due to the fact that antigens injected intramuscularly or subcutaneously virtually do not enter the blood. Injections of preparations based on carcinoembryonal antigen and mucin containing CA 125 antigen to mice induced a standard immune response with predominance of class M immunoglobulins during the early terms and class G immunoglobulins at later terms.

Antitumor activity of specific immunotherapy with mucin containing CA 125 antigen in mice with CaO 1 ovarian carcinoma.

Experiments in CBA mice with transplanted CaO 1 ovarian carcinoma possessing common antigenic determinants with human ovarian carcinoma showed that specific immunotherapy with mucin containing CA 125 antigen inhibited tumor growth by 60% and prolonged animal lifespan by 40-60% in comparison with the control. The correlation coefficient between the tumor size and antibody titer after injection of mucin was -0.4 for IgM and -0.