Antitumor effect of combined treatment of mice with cytostatic agents and bacteriophage T4.

The past few years have shown significant resurgent interest in the old concept of bacteriophage therapy. Some research groups continue to develop whole bacteriophage preparations as alternatives to antibiotic antibacterial treatment. However, improvements in the methods of purification of phage preparations open new opportunities in the successful treatment of antibiotic-resistant bacterial infections. An open question remains on whether bacteriophage preparations (BP) can be safely applied in antibacterial treatment of patients suffering from infections as a consequence of immunosuppression caused by anticancer chemotherapy. The aim of this study was to evaluate the potential modulating effect of bacteriophage T4 preparations administered to mice bearing s.c. or i.v. inoculated B16 melanoma and treated with conventional anticancer drugs, i.e. cyclophosphamide (CY), cisplatin (CPt) or 5-fluorouracil (5-FU). Treatment of mice with (BPT) T4 preparation slightly potentiated the antimetastatic effect of CY. Importantly, no combination of phage-cytostatic treatment resulted in a decrease in the antimetastatic or antitumour effects of an applied drug. This suggests the possibility of safe combination of bacteriophage preparations with popular antitumour drugs.

Protection of animal research subjects.

The use of experimental animals, mostly rodents, in biomedical research and especially in oncology and immunology should be acknowledged with respect, recognizing the contribution of animal experimentation in the fascinating scientific progress in these disciplines of research. It is an obligation of the investigator to justify the scientific and ethical aspects of each study requiring the use of animals. The international guiding principles for using animals in biomedical research are well defined and have been distributed worldwide by the International Council for Laboratory Animal Science (ICLAS) since 1956, when this Organization was founded. In Poland the ICLAS philosophy and principles are highly respected and were implemented firstly by the members of the Commission on Biology of Experimental Animals appointed in 1962 by the Department of Medical Science of the Polish Academy of Science in Warsaw. Animal Protection Acts, first proclaimed in 1928 were gradually modified and improved. Actual legislation (enacted in 1997, 2003 and 2005) is consistent with EU Directives (86/609/EEC) and follows the internationally recommended principles that include ICLAS guidelines concerning animal welfare and care condition in biomedical research. The problem of "alternative methods" is briefly discussed.

Side-chain-modified analogs of calcitriol cause resistance of human HL-60 promyelocytic leukemia cells to drug-induced apoptosis.

Calcitriol and some of its analogs have antiproliferative activity, but at the same time, can cause resistance to apoptosis induced by known cytostatic drugs. In this paper, we examined the effects of treatment with calcitriol or its side-chain-modified analogs, analog of Vitamin D2, coded PRI-1906, with monohomologated and unsaturated side-chain and the analog of Vitamin D3, coded PRI-2191, with (24R) hydroxyl group, and those of known cytostatics (genistein, etoposide, doxorubicin, cisplatin, and taxol) on the apoptosis of HL-60 promyelocytic leukemia cells. HL-60 cells were incubated in three different sequences: (1) pre-treatment with calcitriol or its analogs and then treatment with cytostatics; (2) pre-treatment with cytostatics and then treatment with calcitriol; (3) simultaneous treatment with calcitriol and cytostatics. Apoptosis was examined either by DNA fragmentation in agarose gel electrophoresis or by cell-cycle analysis in a FACS Calibur flow cytometer. We showed that pre-treatment with calcitriol or one of its side-chain-modified analogs PRI-1906 or PRI-2191 caused resistance of HL-60 promyelocytic leukemia cells to genistein-, doxorubicin-, cisplatin-, and taxol-induced apoptosis. Simultaneous exposure of HL-60 cells to calcitriol and drug caused a significant decrease in the apoptotic level of HL-60 cells compared with cells treated with drug alone. The pre-treatment of HL-60 cells with drug and then treatment with calcitriol did not increase the level of apoptosis compared with the drug effect alone. These results indicate the potential limitations of calcitriol analogs for treatment of leukemia.

Genistein alone or combined with cyclophosphamide may stimulate 16/C transplantable mouse mammary cancer growth.

Among the many potential antiangiogenic agents now in various stages of preclinical or clinical study, genistein (GEN) has generated wide interest being because of its natural origin (soybeans) and epidemiological studies showing the cancer chemopreventive effects of soybean consumption. In this paper the in vivo effects of GEN applied either alone or together with cyclophosphamide on the growth of mouse transplantable mammary carcinoma (16/C) transplanted either orthotopically or ectopically is presented. The growth of 16/C mouse mammary cancer transplanted subcutaneously (s.c.) or into the mammary gland (orthotopically-orth.) was stimulated by GEN administered from day 4 after tumor cell inoculation. Such stimulation was not observed when the treatment with GEN was started at day 12 after cell inoculation. Stimulation of tumor growth by GEN was markedly higher in mice transplantedorth. than in those transplanted s.c.. However, GEN did not affect the expression of estrogen (ER)and progesterone receptors (PgR) in the orthotopic model of 16/C cancer. In the case of subcutaneously growing tumors, treatment with GEN lowered (2-fold) the expression of both ER and PgR. In the interpretation of these results, the pleiotropic (including hormonal and antiproliferative), sometimes opposing effects of genistein in vivo should be considered. It seems rather reasonable to exclude breast and, perhaps, other hormone-dependent cancers from the treatment and chemoprevention with soy-derived phytoestrogens until its mechanism(s) of action on various cancer cells is completely understood.

[Genistein: a soy isoflavone revealing a pleiotropic mechanism of action - clinical implications in the treatment and prevention of cancer]. / Genisteina - izoflawonoid soi o zróznicowanym mechanizmie dzialania - implikacje kliniczne w lecznictwie i prewencji chorób nowotworowych.

Genistein, a naturally occurring isoflavonoid, displays antitumor, antimetastatic and antiangiogenic properties, described in various experimental in vitro and in vivo models. The results of several epidemiological studies suggest that soybean consumption may contribute to lower incidence of breast, colon, prostate, thyroid, and head and neck cancers. This protective effect of soy consumption is attributed, among others, to genistein. On the other hand, genistein may enhance the proliferation of some estrogen-positive human breast cancer cells in vivo and the growth of mammary gland and mammary cancer cells in athymic mice. In this paper, various aspects of the diverse biological activities of genistein and their potential clinical implications, especially in the treatment and prevention of cancer, are reviewed and discussed.