Experimental Oncology, 2012 (том 34)

Zinc differentially modulates DNA damage induced by anthracyclines in normal and cancer cells

Sun, 01 Jan 2012 00:00:00 GMT

Zinc differentially modulates DNA damage induced by anthracyclines in normal and cancer cells Wysokinski, D.; Blasiak, J.; Wozniak, K. Zinc is one of the most essential trace elements in human organism. Low blood level of zinc is often noted in acute lymphocytic leukemia (ALL). Treatment with zinc adjuvant is hypothesized to accelerate recovery from ALL, and in conjunction with chemotherapy, cure ALL. Aim: We determined the effect of zinc on DNA damage induced by doxorubicin and idarubicin, two anthracyclines used in ALL treatment. Methods: The experiment was performed on acute lymphoblastic leukemia cell line (CCRF-CEM) and lymphocytes from peripheral blood of healthy, adult subjects. To evaluate the level of DNA damage the comet assay in the alkaline version was used. Results: We observed a significant difference in DNA damage level between normal and cancer cells in the presence of zinc. Cancer cells exhibited a significant increase of DNA damage in the presence of zinc, while in lymphocytes no such effect was observed. Conclusion: Our results suggest that zinc may protect normal cells against DNA-damaging action of anthracyclins and increase this action in cancer cells.

Ukrain, a plant derived semi-synthetic compound, exerts antitumor effects against murine and human breast cancer and induce protective antitumor immunity in mice

Sun, 01 Jan 2012 00:00:00 GMT

Ukrain, a plant derived semi-synthetic compound, exerts antitumor effects against murine and human breast cancer and induce protective antitumor immunity in mice Bozeman, E.N.; Srivatsan, S.; Mohammadi, H.; Daniels, D.; Shashidharamurthy, R.; Selvaraj, P. Despite the recent advances in anti-cancer therapies, breast cancer accounts for the highest percentage of estimated new cases among female cancer patients. The anti-cancer drug Ukrain, a plant-derived semi-synthetic compound, has been shown to be effective in a variety of tumor models including colon, brain, ovarian, melanoma and lymphoma. However, the direct cytotoxic effects of Ukrain have yet to be investigated in breast cancer models. Aim: Herein, we investigated the in vitro and in vivo cytotoxicity of Ukrain using murine (4T07 and TUBO) and human (SKBR-3) breast cancer cell lines. Methods: Cells were treated with varying concentrations of Ukrain for up to 72 h and analyzed for viability by trypan blue exclusion, apoptosis by intracellular caspase 3 and Annexin V staining, and proliferative potential by a clonogenic assay. Female BALB/c mice were challenged subcutaneously (s.c.) with 4T07-RG cells and administered 5 mg/kg or 12.5 mg/kg body weight Ukrain intravenously (i.v.) on the same day and 3 days later. Protective immune responses were determined following re-challenge of tumor-free mice 35 days post primary challenge. Results: Ukrain exposure induced apoptosis in a dose and time-dependent manner with 50 µg/mL Ukrain leading to >50% cell death after 48 h exposure for all three breast cancer cell lines. Ukrain administration (12.5 mg/kg) led to significant inhibition of 4T07 tumor growth in vivo and sustained protective anti-tumor immunity following secondary challenge. Conclusion: Our findings demonstrate the in vitro and in vivo cytotoxic effects of Ukrain on breast cancer cells and may provide insight into designing Ukrain-based therapies for breast cancer patients.

Relationship between NF-κB, ER, PR, Her2/neu, Ki67, p53 expression in human breast cancer

Sun, 01 Jan 2012 00:00:00 GMT

Relationship between NF-κB, ER, PR, Her2/neu, Ki67, p53 expression in human breast cancer Shapochka, D.O.; Zaletok, S.P.; Gnidyuk, M.I. Aim: The aim of the present study was to investigate expression patterns of transcription factor NF-κB (p50 and p65), ER, PR, Her2/neu, Ki-67 and p53 in tumor tissue of patients with breast cancer (BC) and analyze correlation between these markers. Patients and Methods: 62 BC patients previously nottreated with chemo- or radiotherapy were included in the study. All tumors belong to invasive ductal carcinoma of different grade. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Results: The correlation between tumor grade and expression of ER, PR, Ki-67 and p53 was defined. NF-κB expression was found to be changed dependent on expression of ER, PR and p53 and also on molecular subtype (luminal, Her2-positive, hybrid, basal-like). The highest levels of NF-κB, Ki-67 and p53 were found in Her2/neu+ and basal-like tumor subtypes. Conclusion: The increase of nuclear expression of NF-κB correlates with a decrease of expression of steroid hormone receptors (ER and PR), increase of p53 accumulation, and is associated with Her2-positive and basal-like tumor types.

Cytogenetic effects of neutron therapy in patients with parotid gland tumors and relapse of breast cancer

Sun, 01 Jan 2012 00:00:00 GMT

Cytogenetic effects of neutron therapy in patients with parotid gland tumors and relapse of breast cancer Melnikov, A.A.; Vasilyev, S.A.; Musabaeva, L.I.; Velikaya, V.V.; Gribova, O.V.; Startseva, Zh.A.; Urazova, L.N.; Lebedev, I.N.; Choynzonov, E.L. Aim:To assess the frequency and spectrum of chromosome aberrations and micronuclei in peripheral blood lymphocytes of patients with parotid salivary gland tumors and relapse of breast cancer during the course of neutron therapy. Materials and Methods: Samples of peripheral blood were obtained from 9 patients with parotid salivary gland tumors (T3N0–3M0) and 8 patients with relapse of breast cancer before, after first fraction and at the end of neutron therapy. The treatment course specified 5.5–8.4 Gy (equivalent to 23–44 Gy of photon irradiation) with 1.3–2.2 Gy per fraction for patients with parotid salivary gland tumors and 4,8–8.0 Gy (equivalent to 30–40 Gy of photon irradiation) with 1.6 Gy per fraction for patients with relapse of breast cancer. Control group established for conventional cytogenetic analysis consisted of 15 healthy persons. Assessment of chromosome aberrations frequency was performed on routinely stained metaphase plates. Lymphocytes from the same patients were analyzed by micronucleus test in combination with fluorescent in situ hybridization (FISH) using pancentromeric DNA probe. Results: Level of chromosome aberrations and micronuclei significantly increased in lymphocytes of patients from both groups during neutron therapy (P < 0.05). This increase was mainly due to chromosome-type aberrations and centromere-negative micronuclei. The prevalent types of aberrations are in agreement with theoretical mechanisms of neutron effects on cells. Conclusion: Cytogenetic effects of fast neutron therapy in lymphocytes of patients with parotid salivary gland tumors and relapse of breast cancer were observed. A positive dynamics of radiation-induced chromosomal damages formation during the course was denoted in lymphocytes of cancer patients in both groups.