Aim - to study distribution and accumulation of liposomal form of doxorubicin in human breast cancer cells of MCF-7 line and Dox-resistant subline MCF-7/Dox. High performance liquid chromatography and laser confocal microscopy were used. It has been shown that conventional form of doxorubicin was more efficiently delivered to the MCF-7 cells already after 30 min of incubation amounting to its maximum concentration after 4 h. MCF-7/Dox cells are characterized by lower doxorubicin accumulation rate compared with parental cells. The quantity of accumulated liposomal form of doxorubicin is high in MCF-7 cells, and, what is important, Dox-resistant cells accumulated higher levels of liposomal form of doxorubicin than its conventional form. Conclusion: it has been show n that intracellular distribution and accumulation of liposomal forms of doxorubicin in parental and Dox-resistant MCF-7 cells differs from that of conventional doxorubicin.

Aim - to evaluate the efficacy of intraperitoneal vincristine administration into ascitic sarcoma-180 bearing mice as a model of human malignant ascites regarding various peritoneal/retroperitoneal sarcomatosis, and to evaluate the flowcytometric telonierase reverse transcriptase expression for the diagnostic and prognostic purposes. Present study included disease induction by intraperitoneal homologous ascitic sarcoma-180 transplantation followed by in vivo intraperitoneal drug administration to study mitotic index, flowcytometric cell cycle and telonierase reverse transcriptase expression pattern, ervthrosin-B dye exclusion study for malignant cell viability assessment. Besides, in vitro malignant ascite culture in presence and absence of vincristine sulfate and survival study were also taken into consideration. Intraperitoneal vincristine administration (concentration 0,5 mg/kg body weight) significantly diminished the mitotic index in diseased subjects in comparison to untreated control subjects. Treated group of animals showed increased life span and median survival time. Cell viability assessment during the course of drug administration also revealed gradual depression on cell viability over time. Flowcytometric cell cycle analysis showed a good prognostic feature of chemotherapeutic administration schedule by representing high G2/M phase blocked cells along with reduced telomerase reverse transcriptase positive cells in treated animals. Conclusion: we conclude that long term administration of vincristine sulfate in small doses could be a good pharmacological intervention in case of malignant peritoneal ascites due to sarcomatosis as it indirectly reduced the level of telomerase reverse transcriptase expression in malignant cells by directly regulating cell cycle and simultane-ously increased the life expectancy of the diseased subjects.

Aim - leukemia is characterized by uncontrolled marrow cell proliferation and metastatic foci. We investigated the antitumor potential of a nutrient mixture on malignant leukemia P-388 cells. Methods: the nutrient mixture containing lysine, proline, ascorbic acid, green tea extract and other nutrients is formulated to target key pathways in cancer progression. The cells were treated with the mixture, and tested at doses 0, 10, 50, 100, 500 and 1000 mug/ml in triplicates. The effects were evaluated by cell proliferation, Matrigel invasion, cell morphology and apoptosis. The in vivo effect was measured in male nude mice (n = 12) inoculated with P-388 cells. After randomly dividing in two groups, each group was fed regular and the nutrient mixture supplemented diet and the mice were sacrificed after four weeks. The nutrient mixture decreased P-388 cell proliferation at 500 and 1000 mu g/ml. Only 10 % cells were viable at 1000 mu g/ml. Matrigel invasion was significantly inhibited in a dose dependent manner with virtually total inhibition at 1000 mu g/ml. Cell morphological features notably changed with dose increase to 1000 mu g/ml. Analysis of apoptotic cells on live green caspase kit exhibited gradual increase with the increasing dose of the nutrient mixture, and at 1000 mu g/ml 92 % of P-388 cells were in late apoptosis. Tumors in the group of mice supplemented with the nutrient mixture had 50 % lower weight compared to the tumors in control group (p = 0,0105). Histopathologically, both the groups of tumors were similar, yet size of tumors in the group treated with the nutrient mixture was considerably smaller. Conclusion: these results indicate that the nutrient mixture exhibited significant action against multiple targets in P-388 leukemia and may have potential in human leukemia.

Індекс рубрикатора НБУВ: Р56 я431

Рубрики:

Онкологія

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ 

In this review we discuss alarming epidemiological and experimental data on possible carcinogenic effects of long term exposure to low intensity microwave (MW) radiation. Recently, a number of reports revealed that under certain conditions the irradiation by low intensity MW can substantially induce cancer progression in humans and in animal models. The carcinogenic effect of MW irradiation is typically manifested after long term (up to 10 years and more) exposure. Nevertheless, even a year of operation of a powerful base transmitting station for mobile communication reportedly resulted in a dramatic increase of cancer incidence among population living nearby. In addition, model studies in rodents unveiled a significant increase in carcinogenesis after 17 - 24 months of MW exposure both in tumor-prone and intact animals. To that, such metabolic changes, as overproduction of reactive oxygen species, 8-hydroxi-2-deoxyguanosine formation, or ornithine decarboxylase activation under exposure to low intensity MW confirm a stress impact of this factor on living cells. We also address the issue of standards for assessment of biological effects of irradiation. It is now becoming increasingly evident that assessment of biological effects of non-ionizing radiation based on physical (thermal) approach used in recommendations of current regulatory bodies, including the International Commission on Non-Ionizing Radiation Protection (ICNIRP) Guidelines, requires urgent reevaluation. We conclude that recent data strongly point to the need for re-elaboration of the current safety limits for non-ionizing radiation using recently obtained knowledge. We also emphasize that the everyday exposure of both occupational and general public to MW radiation should be regulated based on a precautionary principles which imply maximum restriction of excessive exposure.

Background: the complete medical consequences of the long-term exposure of population to ionizing radiation in post-Chernobyl period are still a controversial issue. The molecular biological analysis of malignant diseases of hematopoietic and lymphoid tissues in contaminated territories requires the precise diagnosis based on criteria of novel classifications. Aim - to analyze the relative gene expression of six apoptosis-related genes in different types of tumors of hematopoietic and lymphoid tissues in patients living in areas of Ukraine contaminated with radionuclides in post-Chernobyl period. The samples of the peripheral blood and bone marrow of 189 Ukrainian leukemia patients and 16 patients with reactive lymphocy tosis were analyzed morphologically and immunocytochemically for precise delineation of the main forms and cytological variants of hematological malignancies according to new WHO classification. Expression of six apoptosis-related genes was analyzed in the individual samples of 9 different groups of malignant diseases of hematopoietic and ly mphoid tissues and one group of patients with reactive lymphocytosis by quantitative RT-PCR. Expression of genes was assessed relative to that in control group of healthy donors. Up-regulation of six analyzed apoptosis-related genes is observed in all groups of leukemia. In most groups of leukemia being analy zed, BCL-2 up-regulation level is superior to that of BAX. Prominent MYC up-regulation is observed in B-lymphoblastic leukemia/lymphoma, non-Hodgkin's lymphoma, and T-lymphoblastic leukemia/lymphoma groups. In myelodysplastic/myeloproliferative neoplasms, the striking up-regulation of Fas-1 and P38MAPK is evident. Practically all the groups of leukemia are characterized by stable high ratios of P53 up-regulation. Conclusion: in Ukrainian patients, up-regulation of six analyzed apoptosis-related genes is observed practically in all types of malignant diseases of hematopoietic and lymphoid tissues under study. Microarray-based analysis of these samples would be of great importance in terms of elucidating genomic interactions in leukemias and their possible association with ionizing radiation.

Індекс рубрикатора НБУВ: Р569.627.7-5

Рубрики:

Пухлини головного мозку та його оболонок

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ 

Індекс рубрикатора НБУВ: Р569.411-52 + Р411.022.3-52

Рубрики:

Пухлини кісткового мозку і крові

Лімфатичні лейкози

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ 

Aim - to study the influence of natural L-asparagine on the efficacy of cytostatic therapy for malignant tumors in experimental investigations. Female C57B1/6 mice weighing 18 - 20 g were selected for the experiments. Lewis' lung carcinoma (LLC) and melanoma B16 cells were used in the study. Animals were inoculated with tumor cells intramuscularly. Solution of L-asparagine in a volume of 0,2 ml per mouse (in appropriate doses) was administered to the animals using gastric probe, daily, for 14 days. Cyclophosphane was administered intraperitoneally in total doses of 180 mg/kg and 90 mg/kg on days 3 and 7 after tumor implantation. The percentage of tumor growth inhibition was calculated and inhibition index and frequency of metastasis were assessed. It has been shown that despite low activity of L-asparagine with regard to primary tumor, the level of metastasis inhibition is rather high (up to 91 % depending on experimental model, therapy regimen and follow-up period). The analysis of previously obtained data and our studies indicate that L-asparagine derived from burdock (Arctium lappa) root has not only its own antimetastatic activity but it is also able to increase antimetastatic activity of cyclophosphane partially reducing toxic effect of cyclophosphane on the organism without decreasing its antitumor and antimetastatic activities. Conclusion: L-asparagine derived from burdock (Arctium lappa) root can be effective in the complex anticancer therapy with the use of appropriate chemotherapy doses and regimens.

Aim - the main purpose of this study was to estimate the SLC34A2 gene expression in normal ovary and different types of ovarian tumors. We have investigated SLC34A2 gene expression level in papillary serous, endometrioid, unspecified adenocarcinomas, benign tumors, and normal ovarian tissues using real-time PCR analysis. Differences in gene expression were calculated as fold changes in gene expression in ovarian carcinomas and benign tumors compared to normal ovary. We have found that SLC34A2 gene was highly expressed in well-differentiated endometrioid and papillary serous ovarian carcinomas compared to low-differentiated endometrioid carcinomas, benign serous cystoadenomas and normal ovary. Analysis of SLC34A2 gene expression according to tumor differentiation level (poor- and well-differentiated) showed that SLC34A2 is up-regulated in well differentiated tumors. Conclusion: upregulation of SLC34A2 gene expression in well-differentiated tumors may reflect cell differentiation processes during ovarian cancerogenesis and could serve as potential marker for ovarian cancer diagnosis and prognosis.

Індекс рубрикатора НБУВ: Р569.452-5

Рубрики:

Пухлини щитоподібної залози

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ 

Індекс рубрикатора НБУВ: Р569.433.3

Рубрики:

Пухлини кишечника

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ 

Індекс рубрикатора НБУВ: Р569.41-52

Рубрики:

Пухлини системи кровотворення, крові та ретикуло-ендотеліальної системи

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ 

The results of own investigations and literature data are summarized to determine the place of the main methods of adsorption therapy in complex treatment of the patients with malignant tumors. New possibilities for the usage of new generation of carbon adsorbents and modern adsorptive technologies in cancer treatment are discussed.

Aim - to study upstream and downstream events in CD150-mediated Akt signaling pathway in normal human B cells, EBVtransformed lymphoblastoid (LCL) and malignant Hodgkin's lymphoma (HL) B cell lines. Methods: to access protein-protein interaction we applied immunoprecipitation, Western blot analysis and surface plasmon resonance (SPR) technique. A novel modification of SPR technique using reduced glutathione bound to golden surface was proposed. Immunostaining and isolation of cytoplasmic fractions and nuclear extracts were performed to detect proteins' localization in cells. Western blot analysis was performed to follow up the phosphorylation of proteins on specific sites and proteins' expression level. It was shown that CD150 ligation induced Akt activation in normal tonsillar B cells (TBC), SH2D1A positive LCL and HL B cell lines. The p85alpha subunit of PI3K co-precipitated with CD150 cytoplasmic tail. This direct association depends on tyrosine phosphorylation and is mediated by N terminal SH2 domain of p85alpha. CD150 initiated phosphorylation of FoxO1 transcription factor in normal B cells as well as in LCL MP-1 and HL cell line L1236. At the same time, CD150 ligation triggered GSK-3beta kinase phosphorylation only in immortalized LCL MP-1 and HL cell line L1236. Conclusions: we have demonstrated that CD150 receptor could trigger PI3K-mediated Akt signaling pathway in normal, EBV-transformed and malignant B cells. CD150-mediated phosphorylation of Akt downstream targets GSK-3beta and FoxO1 in EBV-transformed and HL cells could be one of the mechanisms to avoid apoptosis and support survival program in these immortalized B cells.

Chondrosarcoma is one of the most difficult types of cancers to diagnose and treatment. Therefore, the development of a reliable animal model for chondrosarcoma would be a helpful tool to study of the tumor's growth and progression. Aim - we conducted this study to develop a chondrosarcoma on rat by graft of human chondrosarcoma tumor tissue. Fourteen male Sprague - Dawley rats equally divided in xenograft-implanted and control groups. On the lateral side of the right femur distal 1/3, 5 mm incision was done on the skin after animal anesthesia. Then, was drilled 3 mm on the bone and implanted the xenograft in the bone. Radiography was taken from the operated femur weekly until the fourth week and monthly for 3 months. Four animals of each group were sacrificed after 4 weeks of operation; femur was harvested for histopathological study. Radiological images showed sclerotic area on the implanted bone after 4 weeks of operation. Sections from tumoral areas reveal cartilage forming hypercellular neoplastic tissue with lobular pattern of growth and foci of adjacent tissue invasion such as bone trabeculas and bone marrow. Conclusion: the present study showed that rat xenograft chondrosarcoma can develop by human chondrosarcoma fresh tissue fragments.

Background: tobacco smoking and alcohol drinking generate oxidative DNA damage and may contribute to larynx carcinogenesis. The X-ray repair cross complementing 1 (XRCC1) and excision repair cross-complementing rodent repair deficiency, complementation group 4 (ERCC4(XPF)) genes are important components of DNA excision repair systems, which repair DNA damage induced by various factors, including tobacco smoking and alcohol. Aim - to investigate the association between the genotypes of the XRCC1-Arg399Gln (rs25487) and ERCC4-Arg415GIn (rs 1800067) polymorphisms and smoking- and drinking-related larynx cancer in a Polish population. Methods: The polymorphisms were determined by PCR-RFLP method in 253 patients with squamous cell carcinoma of the larynx and 253 sex- and age-matched controls. We did not find any association between the investigated polymorphisms and larynx carcinoma, dependent on either smoking or drinking status. No association was found between these polymorphisms and larynx cancer grade, stage or age at diagnosis. Conclusions: the results indicated that Arg399Gln polymorphism of XRCC1 gene and Arg-415Gln polymorphism of ERCC4 gene may not be associated with smoking- and drinking-related larynx cancer in Polish population.

The data on the verified cases of mature B-cell neoplasms (chronic lymphocytic leukemia - CLL, B-prolymphocytic leukemia, non-Hodgkin's lymphoma in leukernization phase and multiple myeloma - MM; 146 cases in total) in the consecutive group of Ukrainian clean-up workers within 10 - 25 years after Chernobyl accident are summarized. B-cell neoplasms represent the most prevalent group among all diagnosed neoplasms of hematopoietic and lymphoid tissues in clean-up worker patients under study (49,4 %). MM percentage in the patients of Chernobyl clean-up worker group turned out to be significantly higher than in the patients of the general populations studied at the same period. While the percentage of B-CLL is similar in clean-up worker patients and patients of general population, the trend towards younger age of patients with mature B-cell neoplasms in clean-up worker group is evident. The current concepts on the possible association between mature B-cell neoplasms (mainly B-CLL) and radiation exposure are briefly outlined. Only the precise diagnosis of hematopoietic malignancies combining with large-scale analytical epidemiological studies with careful dose assessment and long-term follow-up may represent the basis for resolving the question whether mature B-cell neoplasms may be radiogenic.

Background: human chromosome arm3p is often affected in various epithelial tumors, and several tumor suppressor genes were recently identified in this region. The most affected is 3p21 region that is 50 - 100 % rearranged in more than 30 types of malignancies, mostly in epithelial cancers: lung, breast, ovarian, cervical, kidney, head and neck, nasopharyngeal, colon etc. These cancers are responsible for 90 % of cancer deaths. Aim - to perform the detailed analysis of 3p (especially 3p21 region) to discover novel potential oncogenes and/or tumor suppressors. To find novel "hot spots" and genes involved in major cancers, dense 3p microsatellite markers (altogether 24) were allelotyped in four epithelial carcinomas (272 patients in total): breast (BC), renal cell (RCC), non-small cell lung (NSCLC) and epithelial ovarian (EOC) cancers. As a main result, a novel region, frequently affected in BC, RCC, NSCLC and EOC was localized between markers D3S2409 and D3S3667 in the 3p21.3. This region (MECA3, major epithelial cancers affected region No. 3) covers numerous UniGene clusters, including genes involved in vital cell functions and carcinogenesis (e.g. MSTI, MSTRI/RON, GPX1 and RHOA). The homozygous deletions were detected in the GPX1 in RCC (12 %, 6 of 50 cases) and BC (1 of 37 cases). At the same time, amplifications and multiplications within the RHOA putative oncogene were identified in BC and RCC. Conclusions: the data suggest that genes with potential oncogenic features are located in the close proximity to putative tumor suppressor gene(s) (TSG(s)) in the MECA3. Multiplication of the RHOA was not reported before. Significant correlation of allelic alterations in the, AP20, MECA3 and LUCA regions with tumor progression was found for some common histological tumor subtypes (e.g. clear cell RCC, and serous EOC).

Aim - to investigate the expression of ABCC11 (MRP8) protein in normal breast tissue, and examine the difference in ABCC11 mRNA and protein expression between normal breast and breast cancer tissues taking into account ABCC 11 genotype (a functional SNP, rsl7822931) and estrogen receptor (ER) status. Sections of paraffin-embedded normal and malignant tissues from 10 patients with invasive ductal carcinoma were used for immunohistochemical analysis. DNA and RNA were extracted from the same sections and used for genotyping and ABCC11 transcript expression measurement by quantitative RT-PCR. A strong expression of ABCC11 was found in epithelial and myoepithelial cells of normal breast lobules and ducts in individuals with different ABCC 11 genotypes. A predominant decrease of ABCC11 expression was observed in malignant tissue compared to normal beast specimen (8 of 10 cases), despite four out of ten tumors showed the elevated ABCC 11 mRNA level as compared to the normal counterpart. Neither ABCC 11 mRNA nor protein expression in normal or cancerous tissue correlated with ER status. Conclusion: the expression of ABCC 11 protein appears to be decreased in most BC. The effect of ABCC11 protein on breast cancer chemosensitivity is likely to be more complex than that which can be directly inferred from ABCC 11 genotype and mRNA expression level in the tumor.