Eksperimental'naia onkologiia最新文献

Aim and methods: The recent discovery of a new isoform of estrogen receptor (ER), ER beta, has promoted the investigation of its expression on mammary gland. This study was carried out to examine the expression of ER alpha, ER beta and proliferating cell nuclear antigen (PCNA) in the carcinogen-induced mammary tumors induced by N-methyl-N-nitrosourea (MNU) or 7,12-dimethylbenz[a]anthracene (DMBA), and to compare these expression with those of age-matched normal mammary glands.

Results: There was significant decrease of expression of ER alpha and ER beta in the mammary gland tumors compared with age-matched normal mammary glands (p < 0.05). In mammary gland tumors, ER alpha expression was mainly located in epithelial cells, showing intranuclear staining pattern. The decrease of ER beta expression was so distant that some tumor cells did not show any expression. There was a complete loss of ER beta expression in 50% (7/14) of MNU-induced mammary gland tumors, and 68.2% (15/22) of DMBA-induced mammary gland tumors. However, there was no difference in PCNA expression between mammary gland tumors and normal mammary glands.

Conclusion: This study represents that the decrease of expression of ER alpha and ER beta is associated with mammary carcinogenesis, and suggests that modulation of ER alpha and ER beta may be the target for the treatment of mammary gland tumors.

Aim: To evaluate the summarized effect of hyperthermia and interleukin-2 (IL-2) administration on antitumor defense in tumor-bearing rats.

Methods: Nonbred rats after subcutaneous inoculation of sarcoma 45 cells were treated with whole-body hyperthermia (WBH, +42.5 degrees C, 60 min) and interleukin-2 (IL-2, 10,000 U/kg of body weight). Parameters of tumor growth and survival of animals were monitored till day 33 after tumor cell inoculation.

Results: Combined application of WBH and IL-2 at 5th day after tumor cell transplantation resulted in a delay of tumor growth and improvement of survival parameters in comparison with control group or animals that received separate treatment. Therapeutic efficacy of WBH combined with IL-2 was analogous to a single-dose chemotherapy with cyclophosphamide.

Conclusion: Combined application of WBH and IL-2 is the useful approach for cancer immunotherapy.

Aim: To investigate surgically resected human brain tumors for the presence of polyomavirus DNA.

Materials and methods: 65 samples of surgically resected human brain tumors (57 tumors were of neuroectodermal genesis, 4--mesenchimal, 4--metastatic tumors) were examined for the presence of viral DNA by PCR analysis.

Results: DNA of polyomaviruses was found in oligodendroligomas (66.7% of cases), oligodendroastrocytomas (66.7% of cases) and glioblastomas (40% of cases). In metastatic tumors viral infection had not been detected. No correlation between the grade of brain tumors and infection with polyomavirus DNA has been revealed.

Conclusion: Our data point to importance of investigation of the brain tumors and cerebrospinal fluid for determination of viral infection.

Aim: To investigate the variation and biological properties of HPV16 E7 isolated from cervical cancer biopsy samples from highest incidence area in HuBei province of China.

Methods: HVP16 E7 sequences isolated from the cervical cancer biopsies of 10 local patients were amplified, sequenced and compared with prototype E7 gene. Then the variant gene was cloned into different vectors to study the antigenicity, expression and immunogenicity of its protein by Western blot, immunofluorescence and genetic immunization in vitro or in vivo.

Results: The results showed that 7 of 10 samples had the same mutations which led to a nonsense mutation at codon 43 of E7 sequence. The truncated E7 protein could be recognized by standard E7 monoclonal antibody in Western blot and expressed in NIH3T3 cells. In the blood sera of mice immunized intramuscularly by the plasmid DNA expressing the variant E7 gene specific E7 antibodies could be detected at week 2, 3, 5 and 6 after inoculation. However, no specific lymphoproliferation after E7 protein stimulation in vitro was detected by MTT colorimetric assay in comparison to the prototype E7 protein.

Conclusion: HPV16 E7 gene may show variation in China and the variant protein could be expressed and induce host humoral immune response, but could not elicit special cellular-immune response against it. These data might hold the key for future development of HPV16 vaccine in HuBei province of China.

Aim: To examine the state of the oxidant-antioxidant system in the liver of guinea pig caused by high doses of ionizing radiation in the early period.

Methods: The research was carried out on guinea pigs irradiated with the doses of 8 Gy (group 2) or 15 Gy (group 3) (single dose/whole body) in comparison with control group (group 1). The levels of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH), the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the levels of selenium in the liver were measured.

Results: TBARS levels in the irradiated animals were markedly higher than those in controls. In group 3, GSH levels and GSH-Px activity were significantly increased while activity of SOD and CAT were significantly decreased compared to groups 1 and 2. Liver selenium levels were not influenced by irradiation.

Conclusion: The data have shown that gamma-irradiation at the doses of 8 Gy or 15 Gy results in significant increase in free radical formation while antioxidant enzymes were affected only at a dose of 15 Gy.

Thousands of research studies have reported that many kinds of cancer cells and tumors can be killed by treatments that increase the concentration of a simple cellular sphingolipid, ceramide (Cer). While there are many ways to elevate tumor Cer levels, this approach is complicated by the central, complex role of Cer in cell homeostasis: Cer is readily metabolized to form other sphingolipids that increase the tumor's growth rate, metastasis, and resistance to the patient's immune system. This review points out the need to prevent this metabolic conversion while simultaneously stimulating the enzymes that increase the formation of Cer. I describe here many of the enzymes that need stimulation or inhibition, and drugs or metabolites or dietary components that modify each of the enzymes. The review also points to the importance of the allylic alcohol group in Cer and in many cancer drugs, suggesting that the hydroxyl group participates in phosphate transfer to and from proteins by forming a temporary phosphate ester. The allylic hydroxyl may also reduce the ketone moieties in mitochondrial ubiquinone, with formation of reactive oxygen species and apoptogenic breakdown. The level of Cer in tumors can be increased by: (1) direct administration of Cer or a Cer analogue, and (2) stimulation of Cer synthesis from its elementary precursors, or from (3) sphingomyelin by hydrolysis, or from (4) the glucosphingolipids by hydrolysis, or (5) by acylation of sphingosine. In addition, Cer concentration can be raised by slowing its conversion to (6) sphingomyelin, (7) glucosylCer, (8) Cer phosphate, and (9) sphingosine + fatty acid by hydrolysis. Therapeutic radiation stimulates the de novo synthesis of Cer in tumors. Conversion of sphingosine (from Cer) to sphingosine phosphate probably also ought to be blocked.

Aim: To compare the sensitivity of doxorubicin (DOX) sensitive and DOX-resistant MC-rhabdomyosarcoma (MC-RMS) cells to the action of lymphokine-activated cells (LAC).

Results: In vitro investigations showed that LAC received from the fraction of adherent lymphocytes possess the highest activity against DOX-resistant tumor cells, and LAC from lymphocytes of total pool--against DOX-resistant tumor cells pretreated with DOX at a low dose. Adoptive immunotherapy of MC-RMS in vivo showed the highest efficacy in the cases of LAC intratumoral injection and the one combined with intraperitoneal administration of DOX at a low dose (increase of survival time by 14% and 25%, respectively).

Conclusion: Adoptive in vivo therapy of DOX-resistant Mh-RMS is effective if LAC or their combination with DOX at a low dose are administered.

Aim: To evaluate oxidative metabolism of rat blood in the course of alveolar hepatic cancer growth in vivo.

Methods: The oxidation imbalance was assessed by the rise in the values of the integral index of oxidation stress. The structural and functional state of erythrocyte membranes was investigated by spin electron paramagnetic resonance spectroscopy.

Results: The growth of alveolar carcinoma was found to be associated with intensification of lipid peroxidation processes with increased blood content of conjugated dienes, malonic dialdehyde against the background of decreased concentration of endogenous antioxidants tocopherol and retinol. Destabilization of the structural state of erythrocyte membranes of rat tumor hosts at the development of oxidation stress was studied, which was characterized by nonspecific structural changes of membrane sorption centres, reduction in specific capacity in the protein-lipid contact area and its increase in the phospholipid bilayer, rise in the degree of order and polarity.

Conclusion: Alveolar carcinoma growth in rats resulted in intensification of free radical lipid peroxidation processes with a shift of the prooxidant-antioxidant balance to the left and development of oxidation stress.

Objective: Activation of transcription factor nuclear factor-kappa B (NF-kappa B) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-kappa B is constitutively activated in human colorectal tumor tissues and, if so, to determine the role of NF-kappa B in colorectal tumorigenesis, furthermore, to determine the association of RelA expression with the expression of cyclooxygenase-2 (COX-2) and tumor cell proliferation.

Methods: Paraffin sections of the normal epithelial, adenomatous and adenocarcinoma tissue were analysed immunohistochemically for RelA, COX-2, Ki-67 protein expression. EMSA (electrophoretic mobility shift assay) was used to confirm the increased nuclear translocation of RelA in colorectal tumor tissues. The expression of COX-2 mRNA was determined by RT-PCR (reverse transcription polymerase chain reaction) analysis.

Results: Activation of NF-kappa B was significantly higher in adenocarcinoma tissue in comparison to that in adenomatous and normal epithelial tissue. The colon tumor cell proliferation, mRNA expression and protein level of COX-2 were significantly increased in the transition from normal to tumor tissue.

Conclusion: Our results suggest that NF-kappa B may promote proliferation via enhancing the expression of COX-2, and the increased expression of RelA/nuclear factor-kappa B plays an important role in the pathogenesis of colorectal carcinoma.

Aim: The aim of the study is to explore the antitumor capacity of effector cells generated from murine splenocytes with sequential addition of a cocktail of cytokines and the possible contribution of dendritic cells to the antitumor capacity of these effector cells.

Methods and results: Interferon-gamma, interleukin (IL)-1 beta, anti-CD3 mAb and IL-2 were used to activate murine splenocytes either from naive mice (termed cytokine activated T cells, CAT) or from DC based vaccine primed mice (termed specific effector T cells, SET). The antitumor roles of SET and CAT were analyzed in murine L615 T lymphocytic leukemia. Both CAT and SET were CD4(+)-predominant phenotypically and didn't show any significant cytotoxicity against a variety of syngeneic and allogeneic target cell lines using 51Cr release assay. When injected in vivo in combination with CY, CAT can cure a large proportion of leukemia mice. The cured mice couldn't establish specific antitumor immunity. However, in contrast to the roles of CAT, SET show far superior antitumor efficacy on a per cell basis compared with CAT. Moreover, the SET cured mice developed tumor specific long term memory immunity which was sufficient to reject a subsequent otherwise lethal tumor cells rechallenge and was transferable to naive immunocompetent mice.

Conclusion: Our data demonstrate that there remain fundamentally different antitumor functions of CAT and SET which might be useful in the immunotherapy strategy choices.