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Biomedical subjects

A Opolski

Publications and source records attributed to A Opolski.

51 records · Page 3Linked to original sources
PubMed1984

Studies on the possibility of induction of anti-H-2 alloreactive cytotoxic antibodies by syngeneic immunization.

Our studies on the syngeneic immunization with normal cells did not confirm the possibility of induction of alloreactive cytotoxic antibodies in this way. We were not able to induce any antibodies after syngeneic immunizations within BALB/c and BALB/cfC3H strains of mice. Anti-H-2 cytotoxic antibodies were raised by syngeneic immunization within BALB/Mo strain of mice, but it was found that this phenomenon was due to the heterogenicity of this strain.

Animals↗
PubMed1981

Expression of Thy1, TL and LYT antigens on spontaneous leukemias of BALB/MO strain of mice.

The expression of Thy1, TL and Tyt antigens on spontaneous BALB/Mo leukemias has been studied. The results obtained thus far indicate that a majority of leukemias express TL antigen and differentiated Lyt phenotype. This observation and other findings demonstrating the existence of TL+ thymocytes with different Lyt phenotypes in normal thymus of young mice lends support for the hypothesis that TL+Lyt2+ phenotype defines this stage in the T cell differentiation pathway, which is particularly sensitive to leukemic transformation.

Animals↗
PubMed1981

Differential expression of murine leukemia antigen on L1210 parental and drug-resistant sublines.

The different expression of surface antigens on L1210 leukemia DBA/2 and drug-resistant L1210 sublines was investigated. Indirect cytotoxic test, the anti-L1210/v alloantiserum reacted more strongly with subline cells than with parental cells. Absorption of the antiserum with Gross cellular surface antigen-positive AKR leukemia (AKSL-4) cells led to a much greater difference in this reactivity. Quantitative absorption experiments revealed that the drug-resistant sublines had 5 times higher absorption capacity than did the parental line. After complete absorption of antibodies against murine leukemia virus-related antigens, the anti-L1210/v alloantiserum still reacted with L1210 cells. This cytotoxicity could be removed after absorption with C3H mammary tumor (MAC-1) cells but not with normal C3H lymphocytes. These results provide evidence that the major cytotoxic activity of the antiserum against L1210 and L1210 subline cells was due to antibodies against murine mammary tumor virus-related antigen and that the drug-resistant sublines of leukemia L1210 have higher quantitative expression of mammary leukemia antigens.

Animals↗
PubMedDate not supplied

Microbial conversion of methyl- and methoxy- substituted derivatives of 5H-indolo[2,3-b]quinoline as a method of developing novel cytotoxic agents.

In furtherance of our structure-activity relationship studies on the antitumor activity of indolo[2,3-b]quinolines, novel cytotoxic derivatives bearing methyl groups at N-5, C-11, C-2 and/or C-9, as well as methoxy-groups at C-2 and/or C-9, were synthesized by the modified Graebe-Ullmann reaction. To elucidate the metabolic pathways of these compounds, zygomycete fungus Cunninghamella elegans ATCC 9245 (which is known to produce drug metabolites that are also formed in mammals) was used as a mimetic organism. Simultaneously, biotransformation of the same substrates was carried out with a microsomal fraction of rat liver. Three forms of microbial conversion were observed: hydroxylation of the aromatic ring or hydroxylation of the methyl group, and O-demethylation. The reaction proceeded regioselectively, and only positions C-2 and C-9 were affected in the indolo[2,3-b]quinoline system. The products formed were found to be identical with the metabolites generated by rat liver microsomes. The metabolites obtained displayed a cytotoxic activity in vitro against colon adenocarcinoma SW-707 and lung carcinoma A-549 (ID50 in the range 0.27-3.04 microM), which was as strong as that of the substrates. In the course of the further metabolic pathway study of indolo[2,3-b]quinolines we found that metabolites with a hydroxyl group in the aromatic system were transformed to non-cytotoxic polymeric products by multicopper oxidases: human ceruloplasmin or fungal laccase (used as mimetic enzyme), whereas metabolites with a hydroxymethyl group did not undergo such bioconversion. The last mentioned compounds can be regarded as a novel type of cytotoxic indolo[2,3-b]quinoline derivatives formed in metabolic processes.

Animals↗
PubMedDate not supplied

Antiproliferative activity in vitro of side-chain analogues of calcitriol against various human normal and cancer cell lines.

The antiproliferative in vitro activity of side-chain modified analogues of 1,25-dihydroxyvitamin D3 was examined in order to select compounds with potential antitumour activity. Analogues PRI-1906, PRI-1907, PRI-1909, PRI-2191, PRI-2192, PRI-2193 and PRI-2194 were examined for their antiproliferative activity in vitro against a spectrum of various human cancer cell lines using the MTT technique. In addition, analogues PRI-1906 and PRI-2191 were screened against cells of human leukaemia HL-60 line and against normal human skin fibroblasts. Calcitriol and these two analogues revealed strong antiproliferative activity against these two targets with maximal growth inhibition of 68% for HL-60 cells and of 60% for fibroblasts, and this effect was dose dependent. All analogues tested, except PRI-1909, revealed antiproliferative activity against human carcinoma cell lines of breast origin applied, namely against T47D and MCF-7. The maximal growth inhibition of 49% for T47D cell line and 39% for MCF-7 line was observed, and this effect was dose dependent. The inhibitory doses of the analogues tested were compared with the indices for calcitriol. Analogue PRI-1906 revealed the strongest antiproliferative activity against these four target cell lines (HL-60, fibroblasts, MCF-7, and T47D). The novel analogues of calcitriol, similarly to calcitriol, appeared to be not active against other human cancer cell lines tested (including those originated from lung, colon, prostate, urinary bladder, ovary, pancreas, stomach and kidney) revealing an antiproliferative activity not exceeding 20%. The mechanism of the observed antiproliferative effect of calcitriol and its analogues in vitro remains unclear, however, it may be related to their effect on cell differentiation. The appearance of antigen CD14 and CD11b expression after exposure to calcitriol and its new analogues confirmed their effect on cell differentiation.

Antineoplastic Agents↗
PubMedDate not supplied

Metastatic potential of human uroepithelial cancer cells is not dependent on their adhesion to E-selectin.

In our previous studies we have found that human uroepithelial cell lines differ in their expression of sialosyl LewisA antigen. We have also shown that among the studied cell lines, only Hu 1703He cells with the highest expression of this tetrasaccharide bind to E-selectin-expressing cells. In the present study we put forward the question, of whether sialosyl LewisA-mediated adhesion of uroepithelial cells to E-selectin is important in the formation of metastases. The HCV 29T and Hu 1703He cells, representing two uroepithelial cell lines, were transplanted into NCr nu/nu mice. Hu 1703He cells express on their surface a high level of sialosyl LeA antigen, while HCV 29T cells are sialosyl LewisA-negative. We have shown that human uroepithelial cancer cells, in addition to their tumorigenic and invasive properties, are highly metastatic when inoculated into athymic nu/nu mice. The ability to form secondary tumour foci in lung and liver seems to be independent of the expression of sialosyl LewisA antigen.

Animals↗
PubMedDate not supplied

Antitumour and antimetastatic effect of genistein alone or combined with cyclophosphamide in mice transplanted with various tumours depends on the route of tumour transplantation.

In the present study we evaluated the antitumour effect of genistein alone, cyclophosphamide alone and as a combined therapy with both agents in mice transplanted with B16F-10 melanoma and Lewis lung cancer cells. The influence of the route of inoculation of the tumour cells on the antitumour and antimetastatic effects of these therapeutics was evaluated. The antitumour effect of genistein in mice with B16F-10 intradermically (i.d.) growing tumours and in mice with LL2 subcutaneous (s.c.) tumours was observed. In addition, its antimetastatic effect (reduction of lung colonies) in mice inoculated intravenously (i.v.) with B16F-10 and in mice with LL2 cells injected either intravenously or subcutaneously was observed. No life span prolongation of mice injected intraperitoneally (i.p.) with B16F-10 cells was observed, either after treatment with genistein alone or with cyclophosphamide alone. The synergistic effect of both agents in combined treatment, when the cells of B16F-10 melanoma were injected i.p., i.v. or i.d. and in a weaker manner when the cells of LL2 cancer were injected s.c., was observed. When LL2 cells were injected intravenously, no additive effect of genistein and CY could be detected. In conclusion, we have described the experimental mouse tumour models in which both the antitumour and antimetastatic effects of genistein alone, CY alone and those of combined therapy with genistein and cyclophosphamide were dependent on the implantation route of the tumour cells.

Animals↗
PubMedDate not supplied

Antitumor effect of electrochemical therapy on transplantable mouse cancers.

The aim of our study was to assess the antitumor effect of electrochemical therapy (ECT) in the mice bearing advanced transplantable tumours. Mouse mammary cancer 16/C (group 1) and fibrosarcoma F69-3 (group 2) were transplanted subcutaneously (s.c.) into the C3H or BALB/c mice, respectively. Twenty animals in each group bearing measurable s.c. tumours were randomly divided into two subgroups (experimental and control). Two electrodes were inserted into tumours and low level direct current (6-7 V, 5-21 mA) was passed. The animals were observed and tumors were measured twice a week. The animals were sacrificed and autopsied when the tumor diameter reached 2.0 cm. Two animals of each group (experimental and control) were sacrificed for histopathological tumor examination on the 1st and 6th day after ECT. A significant inhibition of tumor growth in mice subjected to ECT was observed, both in those with s.c. growing mammary cancer and with fibrosarcoma. This inhibition was associated with marked prolongation of survival time of ECT-treated mice. It appeared that the mice with mammary cancers were more susceptible to ECT therapy than those with growing s.c. fibrosarcoma. The histopathological studies of tumor specimens from ECT-treated mice showed extensive foci of necrosis with shrinkage of cell nuclei deprived of chromatin. In conclusion, the treatment which inhibits the growth of experimental mammary and fibrosarcoma tumors was demonstrated. However, in no mice complete regression of tumours was observed.

Adenocarcinoma↗
PubMedDate not supplied

Potentiation of the antiproliferative effect in vitro of doxorubicin, cisplatin and genistein by new analogues of vitamin D.

Numerous vitamin D3 analogues have been synthesised in recent years in order to obtain compounds with a favourable biological and therapeutic (antipsoriatic and/or antitumour) activity. Our results showed that pre-treatment for 72 hours of HL-60 human promyelocytic leukaemia cells with calcitriol or its new analogues significantly potentiated their sensitivity to the antiproliferative effect in vitro of cisplatin, doxorubicin or genistein. Moreover, for all cytotoxic agents tested a synergistic antiproliferative effect was observed. This effect was expressed as a significant decrease of the ID50 (inhibitory dose 50%) values for each cytotoxic agent applied after pretreatment with calcitriol or its analogues of HL-60 cells in comparison with the effect of cytotoxic agent applied alone. The observed in vitro potentiated antiproliferative effect of cytotoxic drugs used in combination with vitamin D or its analogues may raise the question as to whether such an effect could be expected in the in vivo situation.

Antineoplastic Agents↗
PubMedDate not supplied

Antiangiogenic and antitumour effects in vivo of genistein applied alone or combined with cyclophosphamide.

The antitumour and antiangiogenic effects in vivo of genistein, applied alone or in combined therapy with cyclophosphamide, in the Lewis lung carcinoma (LL2) and B16 melanoma mouse tumour models, were analysed. Our own new method, allowing quantification of the volume of blood present in tumour tissue, enabled estimation of the degree of vascularization. Tumour cells entrapped in alginate beads were injected subcutaneously into mice. The quantification of alginate implant vascularization was performed with 125I-labeled mouse albumin injected intravenously. In mice bearing transplantable Lewis lung cancer the additive antiangiogenic, but not cytostatic, effect of genistein combined with cyclophosphamide (CY) was observed, since the treatment with genistein alone reduced tumour blood supply in 35% (tumour weight in 36%), with CY in 38% (tumour weight in 70%) and with both compounds in 61% (tumour weight in 75%). In the B16 melanoma model the respective values were: 60 and 44% for genistein, 83 and 79% for CY and 76 and 74% for combined treatment. These results indicate a higher antiangiogenic rather than cytostatic effect of genistein in both mouse tumour models applied.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Methoxy- and methyl-, methoxy-5,6,11-trimethyl-6H-indolo [2,3-b]quinolinium derivatives as novel cytotoxic agents and DNA topoisomerase II inhibitors.

New members of the cytotoxic indolo[2,3-b]quinoline family, with a methyl groups at N-5, N-6 (their presence stabilizes the positive charge of the molecule), were prepared using a modified Graebe-Ullmann reaction. The derivatives obtained were well soluble in water in a non-pH-dependent manner. They displayed strong antimicrobial activity against Gram-positive bacteria and pathogenic fungi (the MIC values fall between 0.0025 and 0.12 mM) and highly selective cytotoxicity in vitro against different human cancer cell lines: colon adenocarcinoma SW 707, lung carcinoma A 549, transitional cell carcinoma Hu 1703, and oral epidermoid carcinoma KB, in the range of 0.01 to 3.0 microM. They also stimulated the formation of topoisomerase-II-mediated DNA cleavage at concentration from 0.04 to 0.5 microM. These observations correspond well with the ability of the tested compounds to increase the melting temperature of calf thymus DNA (delta Tm being between 13 degrees C and 22 degrees C).

Animals↗
PubMedDate not supplied

Synthesis of new derivatives of 4-methyl-5-ethoxalyl-1H-2,3,4,5- tetrahydro-1,5-benzodiazepin-2-one and their psychotropic and anti-proliferative activities.

5-Ethoxalyl-4-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepin -2-one [I] was treated with some selected secondary amines (dimethyl-, diethyl-, dipropyl-, disobutylamine or with morpholine) and methyl-hydrazine. Amides II-IV and hydrazide VII were obtained. Compounds II, IV and VI were tested for their psychotropic activity; they showed a weak toxicity. Compounds II and VI showed an anxiolytic activity. Compounds I, II, IV, VI and VII were screened for their cytotoxic (anti-proliferative) activity in vitro by using different human cancer cell lines. None of them revealed any inhibiting effect against the tumor lines used.

Animals↗