The digestive system of the stony coral Stylophora pistillata.

Because hermatypic species use symbiotic algal photosynthesis, most of the literature in this field focuses on this autotrophic mode and very little research has studied the morphology of the coral's digestive system or the digestion process of particulate food. Using histology and histochemestry, our research reveals that Stylophora pistillata's digestive system is concentrated at the corals' peristome, actinopharynx and mesenterial filaments (MF). We used in-situ hybridization (ISH) of the RNA transcript of the gene that codes for the S. pistillata digestive enzyme, chymotrypsinogen, to shed light on the functionality of the digestive system. Both the histochemistry and the ISH pointed to the MF being specialized digestive organs, equipped with large numbers of acidophilic and basophilic granular gland cells, as well as acidophilic non-granular gland cells, some of which produce chymotrypsinogen. We identified two types of MF: short, trilobed MF and unilobed, long and convoluted MF. Each S. pistillata polyp harbors two long convoluted MF and 10 short MF. While the short MF have neither secreting nor stinging cells, each of the convoluted MF display gradual cytological changes along their longitudinal axis, alternating between stinging and secreting cells and three distinctive types of secretory cells. These observations indicate the important digestive role of the long convoluted MF. They also indicate the existence of novel feeding compartments in the gastric cavity of the polyp, primarily in the nutritionally active peristome, in the actinopharynx and in three regions of the MF that differ from each other in their cellular components, general morphology and chymotrypsinogen excretion.

[The detection of highly-transmissible genotypes of agent in clinical samples for prognosis of unfavorable course of tuberculosis.]

The bio-information search was carried out and the design of primers and TaqMan probes was developed to detect DNA of agent of tuberculosis subtypes CC1 and CC2-W148 of Beijing genotype and also Ural genotype in various clinical material (phlegm, spinal fluid, pleural fluid, etc.) using real-time polymerase chain reaction technique. The 180 clinical samples from 143 patients with tuberculosis of lungs were used to carry out an approval of sensitivity and specificity of the developed tests concerning studies at the genetic analyzer GeneXpert. The sensitivity of tests on CC1, CC2-W148 и Ural relating to polymerase chain reaction of analyzer Gene Expert made up to 91%, 106% and 81% correspondingly. In all cases, the specificity made up to 100%. In parallel studies the samples with DNA of СС2-W148 genotype were more often positive on mutation of resistance to Rifampicin-Rif (+) according the results of GeneXpert (χ² = 27,1; p < 0,01) related to other genotypes. At the same time, detection of СС2-W148 strain in patient was more often accompanied by discrepancy of results: GeneXpert - Rif (+) and resistance to Rifampicin in bacteriological study under ultimate validation of multiple medicinal resistance of tuberculosis (χ² = 5,1; p < 0,05). The analysis was applied to negative effect of combination of allele-336G of CD209 gene of patient with genotype of tuberculosis mycobacterium Beijing detected previously (Ogarkov et al., 2012). The significant prevalence was observed related to widespread medicinal resistance (χ² =4,3; p < 0,05) in patients with allele-336G of CD209 gene in combination with CC2-W148 clone in comparison with other combinations in patients. The obtained results testify a possibility of application of genetic typing of tuberculosis agent and patient for early diagnosis of development of various complications of tuberculosis at the stages of primary examination of primarily detected patients with tuberculosis.

[Interaction of Dystamycin Dimeric Analog with Poly(dA) x poly(dT), Poly[d(A-T)] x poly[d(A-T)] and Duplex O23 at Origin of Replication of the Herpes Simplex Virus].

The binding of distamycin dimeric analog (Pt-bis-Dst) to poly[d(A-T)] x poly[d(A-T)1, poly(dA) x poly(dT) and duplex O23 with the sequence 5'-GCCAATATATATATATTATTAGG-3' which is present at the origin of replication of herpes simplex virus OriS is investigated with the use of UV and CD spectroscopy. The distinction of the synthetic polyamide from a natural antibiotic lies in the fact that in the synthetic polyamide there are two distamycin moieties bound via a glycine cis-diamino platinum group. It was shown that the binding of Pt-bis-Dst to poly[d(A-T)] x poly[d(A-T)] and poly(dA) x poly(dT) reaches saturation if one molecule of the ligand occurs at approximately every 8 bp. With further increase in the ratio of the added ligand to the base pairs in CD spectra of complexes with poly[d(A-T)] x poly[d(A-T)], we observed that the maximum wavelength band tend to be shifted towards longer wavelengths, while in the spectral region of 290-310 nm a "shoulder", that was absent in the spectra of the complexes obtained at low polymer coverages by the ligand, appeared. At high molar concentration ratios of ligand to oligonucleotide Pt-bis-Dst can bind to poly[d(A-T)] x poly[d(A-T)] in the form of hairpins or may form associates by the interaction between the distamycin moieties of neighboring molecules of Pt-bis-Dst. The structure of the complexes is stabilized by interactions between pirrolcarboxamide moieties of two molecules of Pt-bis-Dst adsorbed on adjacent overlapping binding sites. These interactions are probably also responsible for the concentration-dependent spectral changes observed during the formation of a complex between Pt-bis-Dst and poly[d(A-T)] x poly[d(A-T)]. Spectral changes are almost absent in binding of Pt-bis-Dst to poly(dA) x poly(dT). Binding of Pt-bis-Dst to duplex O23 reaches saturation if two ligand molecules occur in a duplex that contains a cluster of 18 AT pairs. With increasing the molar concentration ratio of the ligand to the duplex CD spectra undergo concentration-dependent changes similar to those observed during binding of Pt-bis-Dst to poly [d(A-T)] x poly[d(A-T)]. Testing for antiviral efficacy of Pt-bis-Dst showed that the concentration, at which the cytopathic effect produced by the herpes simplex virus in cell culture Vero E6 halved, is equal to 1.5 µg/ml and the selectivity index for evaluating antiviral activity is 65 at a relatively low cytotoxicity. The concentration of Pt-bis-Dst, at which approximately half the cells are killed, is equal to 100 µg/ml.

Efficiency of recombinant thymosin ß4 in spontaneous mouse model of chronic dermatitis.

The therapeutic efficiency of recombinant thymosin ß4 (rTß4) synthesized by us was studied in vivo on spontaneous CBRB mouse model that is adequate to human chronic dermatitis. Three applications of the drug during a week significantly alleviated symptoms of the disease in female mice, and in complex with subsequent antibacterial and antifungal therapy led to a pronounced and lasting (2 months) therapeutic effect. The results attest to a possibility of using rTß4 in combination with the known treatment protocols for chronic inflammatory diseases of the skin.

[Rational approach to administration of combination therapy in arterial hypertension: modern recommendations and personal experience].

Modern treatment of arterial hypertension (AH) in based on concept of necessity of arterial pressure (AP) lowering to target levels for prevention of cardiovascular (CV) diseases (D) and reduction of cardiovascular mortality. AP <140/90 and <140/80-85 mm Hg are target levels for general population and patients with diabetes, respectively. Most patients should be initially prescribed combination therapy as in ambulatory practice mainly patients from high and very high risk groups are observed. Prescribing combination therapy one should take into consideration not only category of risk of CVD development but also AP level, i.e. degree of AH. It is not expedient to always start combination therapy with low doses of preparation because administration of such therapy in patients with 2-3 degree AH inevitably leads to necessity of further elevation of doses and lengthening of time to achievement of target AP. It should be mentioned that achievement of target AP is possible with continuation of therapy with higher dose of same combination without addition of third drug. Rational pharmacotherapy of AH implies concentration of efforts on consideration of not only AP but also of factors of risk of development of CV complications (C) especially on detection of symptomless target organs damage and clinical complications for assessment of total of CVC development because of recent update of data on prognostic significance of symptomless damage of target organs including heart, blood vessels, kidney, eyes, and brain.

[1,10-phenantroline europium complexes: their inclusion in liposomes and cytotoxicity].

For a series of 1,10-phenantroline tris-beta-diketonate europium complexes (EuC), cytotoxic activity on the HBL-100 human breast carcinoma cells was determined. Liposomal preparation of the most active EuC, V12, was also tested for cytotoxicity. Testing of this preparation in vivo on starting lethal murine model of T cell leukemic lymphoma ASF-LL showed that the inclusion of V12 in liposomes did not increase its antitumour activity in a local mode of administration.

[The order of the bs, Skdh, and Aadh1 genes in chromosome 5R of rye Secale cereale L].

Segregation analysis was performed in the progenies obtained in analyzing crosses of hybrids of spring and winter accessions of rye Secale cereale L. and wild S. montanum subsp. anatolicum (Grossh.) Tzvel. (syn. S. strictum (J. Presl) J. Presl). The test genes controlled the brittle stem (bs), the allelic variants of aromatic alcohol dehydrogenase (Aadh 1) and shikimate dehydrogenase (Skdh), and the growth habit (Vrn 1). A linkage was observed in the inheritance of the brittle stem and the aromatic alcohol dehydrogenase and shikimate dehydrogenase alloenzymes. The order of genes was established to be bs-Skdh-Aadh 1, and the genetic distances were estimated to be bs-(9.0%)-Skdh, bs-(10.8%)-Aadh 1, and Skdh-(5.3%)-Aadh 1. The recombination coefficient between the Skdh and Aadh 1 genes varied from 2.2 to 18.2%, averaging 5.3%. The growth habit was inherited independently of the bs-Skdh-Aadh 1 linkage group.

[Criteria for the effectiveness of interleukin-2 immunotherapy in a spontaneous murine mammary tumor model].

A novel approach is suggested to identify more homogenous subgroups involved in the follow-up of growth of spontaneous mammary tumors in mice (116, history-based analysis). That depends on subclinical period (preneoplastic and non-invasive stages of tumor growth) as well as rate of growth after clinical manifestation. An analysis of tumor growth rate versus survival of experimental and control animals after primary diagnosis and clinical manifestation of tumor showed that following a single peritumoral 2.5 x 10(6) IU IL-2 treatment tumor growth slowed down (n = 29; p < or = 0.05) while survival tended to improve. Originally fast-growing tumors without significant subclinical stage continued to grow but slowly. Females with such tumors survived longer than untreated controls without showing, however, any improvement on that parameter.

Hypoxia selectively induces proliferation in a specific subpopulation of smooth muscle cells in the bovine neonatal pulmonary arterial media.

Medial thickening of the pulmonary arterial wall, secondary to smooth muscle cell (SMC) hyperplasia, is commonly observed in neonatal hypoxic pulmonary hypertension. Because recent studies have demonstrated the existence of multiple phenotypically distinct SMC populations within the arterial media, we hypothesized that these SMC subpopulations would differ in their proliferative responses to hypoxic pulmonary hypertension and thus contribute in selective ways to the vascular remodeling process. Expression of meta-vinculin, a muscle-specific cytoskeletal protein, has been shown to reliably distinguish two unique SMC subpopulations within the bovine pulmonary arterial media. Therefore, to assess the proliferative responses of phenotypically distinct SMC subpopulations in the setting of neonatal pulmonary hypertension, we performed double immunofluorescence staining on pulmonary artery cryosections from control and hypertensive calves with antibodies against meta-vinculin and the proliferation-associated nuclear antigen, Ki-67. We found that, although neonatal pulmonary hypertension caused significant increases in overall cell replication, proliferation occurred almost exclusively in one, the meta-vinculin-negative SMC population, but not the other SMC population expressing meta-vinculin. We also examined fetal pulmonary arteries, where proliferative rates were high and meta-vinculin expression again reliably distinguished two SMC subpopulations. In contrast to the hypertensive neonate, we found in the fetus that the relative proliferative rates of both SMC subpopulations were equal, thus suggesting the existence of different mechanisms controlling proliferation and expression of cytoskeletal proteins in the fetus and neonate. We conclude that phenotypically distinct SMC populations in the bovine arterial media exhibit specific and selective proliferative responses to neonatal pulmonary hypertension. Distinct SMC subpopulations may, thus, contribute in unique ways to vascular homeostasis under both normal and pathologic conditions.

[Genetic control of the spring habit in old local cultivars and landraces of common wheat from Siberia].

The inheritance of the spring habit was studied in 63 old local cultivars and landraces of common wheat from Eastern and Western Siberia and the Tyva Republic. Minimal polymorphism was observed for the dominant Vrn genes, controlling the spring habit in landraces of these regions. The control was digenic and involved the Vrnl and Vrn2 dominant genes in the majority (95%) of cultivars and was monogenic in three cultivars. None of the cultivars had the Vrn3 dominant gene, characteristic of the neighboring regions of China and Central Asia. Among 137 old local cultivars and landraces of Siberia, only one (cultivar Sibirskaya (k-23347) from Irkutsk oblast, was comparable in the response to the natural short day (photoperiod) to Chinese cultivars. Comparison of the results and the data reported for commercial cultivars revealed that the genotype frequencies of the dominant Vrn genes in Siberian landraces and commercial cultivars of common wheat remained essentially unchanged at least for the past 100 years. At the same time, Siberian landraces significantly differed in Vrn dominant gene frequencies from cultivars of the adjacent regions. It was assumed that the control of the spring habit by the two Vrn dominant genes is optimal for the climatic conditions of Siberia.

Targeting Holliday junctions by origin DNA-binding protein of herpes simplex virus type 1.

In the present paper, the interactions of the origin binding protein (OBP) of herpes simplex virus type 1 (HSV1) with synthetic four-way Holliday junctions (HJs) were studied using electrophoresis mobility shift assay and the FRET method and compared with the interactions of the protein with duplex and single-stranded DNAs. It has been found that OBP exhibits a strong preference for binding to four-way and three-way DNA junctions and possesses much lower affinities to duplex and single-stranded DNAs. The protein forms three types of complexes with HJs. It forms complexes I and II which are reminiscent of the tetramer and octamer complexes with four-way junction of HJ-specific protein RuvA of Escherichia coli. The binding approaches saturation level when two OBP dimers are bound per junction. In the presence of Mg2+ ions (≥2 mM) OBP also interacts with HJ in the stacked arm form (complex III). In the presence of 5 mM ATP and 10 mM Mg2+ ions OBP catalyzes processing of the HJ in which one of the annealed oligonucleotides has a 3'-terminal tail containing 20 unpaired thymine residues. The observed preference of OBP for binding to the four-way DNA junctions provides a basis for suggestion that OBP induces large DNA structural changes upon binding to Box I and Box II sites in OriS. These changes involve the bending and partial melting of the DNA at A+T-rich spacer and also include the formation of HJ containing Box I and Box II inverted repeats and flanking DNA sequences.

[Analysis of Proliferation and Survival of Agrobacteria after Inoculation of Maize Pistil Filaments].

While the authors have previously developed a method of pistil filament treatment with Agrobacterium cells during blossoming for the transformation of maize generative cells, the mechanism for bacterial T-DNA penetration into the embryo sac remained unknown. This article analyzes the possibility of agrobacterial penetration into the maize embryo via pollen tubes. Microbiological, PCR, and GUS techniques were used to confirm that agrobacteria could spread for up to 20 cm from the sie of inoculation and were detected in maize embryo tissues as aerly as 24 h after inoculation, while they were not revealed after 5-13 days.

Administrative interventions associated with increased initiation on antiretroviral therapy in Irkutsk, Siberia.

A bundle of initiatives to integrate human immunodeficiency virus (HIV) and tuberculosis (TB) services was assessed for the impact on antiretroviral therapy (ART) initiation at a TB referral hospital in Irkutsk, Russian Federation, from February 2014 to December 2015. The ART initiation rates in 166 ART-naïve patients undergoing anti-tuberculosis treatment (34.1% with multidrug or extensively drug-resistant TB) increased significantly from 14 (17%) pre-intervention to 44 (54%) post-intervention (P < 0.001). A survey of TB hospital staff identified administrative prioritisation as the most important initiative for increasing ART initiation.

Un ensemble d'initiatives visant à intégrer les services relatifs au virus de l'immunodéficience humaine (VIH) et à la tuberculose (TB) a été évalué en termes d'impact sur la mise en route du traitement antirétroviral (TAR) dans un hôpital de référence de la TB à Irkoutsk, Fédération de Russie, entre février 2014 et décembre 2015. Les taux de mise en route du TAR chez 166 patients n'en ayant jamais reçu et traités pour TB (34,1% avec une TB multi-résistante ou ultra-résistante) ont significativement augmenté de seulement 14 (17%) avant l'intervention à 44 (54%) après l'intervention (P < 0,001). Une enquête auprès du personnel de la TB a identifié la priorisation administrative comme l'initiative la plus importante dans l'augmentation de l'initiation du TAR.

Se evaluó un conjunto de iniciativas encaminadas a integrar los servicios de atención de la infección por el virus de la inmunodeficiencia humana (VIH) y la tuberculosis (TB), con el objeto de determinar la repercusión de la integración sobre el comienzo del tratamiento antirretrovírico (TAR) en el hospital de referencia de la TB de Irkutsk, en la Federación de Rusia, de febrero del 2014 a diciembre del 2015. La tasa de iniciación del TAR en 166 pacientes que nunca lo habían recibido y que estaban en curso de tratamiento antituberculoso (34,1% con TB multirresistente o extremadamente multirresistente) aumentó de manera significativa de solo 14 pacientes antes de la intervención (17%) a 44 pacientes después de la misma (54%; P < 0,001). Al interrogar al personal encargado de la TB en este hospital de referencia, se puso en evidencia que la priorización administrativa del TAR constituía la iniciativa de más había influido en el incremento de su utilización.

Polymer-bound 6' sialyl-N-acetyllactosamine protects mice infected by influenza virus.

To develop a mouse model for testing receptor attachment inhibitors of human influenza viruses, the human clinical virus isolate in MDCK cells A/NIB/23/89M (H1N1) was adapted to mice by serial passaging through mouse lungs. The adaptation enhanced the viral pathogenicity for mice, but preserved the virus receptor binding phenotype, preferential binding to 2-6-linked sialic acid receptors and low affinity for 2-3-linked receptors. Sequencing of the HA gene of the mouse-adapted virus A/NIB/23/89-MA revealed a loss of the glycosylation sites in positions 94 and 163 of HA1 and substitutions 275Asp-->Gly in HA1 and 145Asn-->Asp in HA2. The four mouse strains tested differed significantly in their sensitivity to A/NIB/23/89-MA with the sensitivity increasing in the order of BALB/cJCitMoise, C57BL/6LacSto, CBA/CaLacSto and A/SnJCitMoise strains. Testing of protective efficacy of the polyacrylamide conjugate bearing Neu5Acalpha2-6Galbeta1-4GlcNAc trisaccharide under conditions of lethal or sublethal virus infection demonstrated a strong protective effect of this preparation. In particular, aerosol treatment of mice with the polymeric attachment inhibitor on 24-110 h after infection completely prevented mortality in sensitive animals and lessened disease symptoms in more resistant mouse strains.

Adhesion receptors of vascular smooth muscle cells and their functions.

Vascular smooth muscle cells (SMCs) are present in several phenotypic states in blood vessels. They show a high degree of plasticity, undergoing rapid and reversible phenotypic changes in response to environmental stresses and vascular injury. Thereby, SMCs play an important role in development of atherosclerosis and restenosis after angioplasty and coronary bypass grafting. Many functions of SMCs, such as adhesion, migration, proliferation, contraction, differentiation and apoptosis are determined by surface adhesion receptors involved in cell-cell binding and interactions between cells and extracellular matrix (ECM) proteins. Some cell adhesion receptors are involved in intracellular signalling and participate in cellular response to different stimuli. The adhesion receptors of vascular SMCs discussed here include the ECM adhesion receptors integrins, alpha-dystroglycan and syndecans, as well as the cell-cell adhesion receptors cadherins and cell adhesion molecules. This review is intended to provide a generalised overview of the receptors expressed in vascular SMCs in relation to their functions and implications for vascular pathology.

Galectin 1 is involved in vascular smooth muscle cell proliferation.

OBJECTIVE: Smooth muscle cell (SMC) migration and proliferation are the key steps in the development of atherosclerosis and restenosis. Matricellular proteins have been implicated in cell adhesion, migration and proliferation. Here we investigated the role of the matricellular protein galectin-1 (Gal-1), a beta-galactoside-binding lectin, in SMC proliferation in atheroma and DNA synthesis in cell culture. METHODS: Protein expression was visualised by tissue section immunostaining. RNA expression was analysed using Northern blot analysis. DNA synthesis of human vascular SMCs was determined by 3H-thymidine incorporation. Recombinant glutathione S-transferase-galectin-1 fusion protein (Gal FP) binding to extracellular matrix (ECM) proteins was measured by ELISA. Gal-1 binding to cells and ECM was estimated using 125I-labelled Gal FP. RESULTS: Prominent Gal-1 staining coincided with SMC proliferation in human coronary endarterectomy samples in organoid culture. In cell culture, Gal-1 mRNA was upregulated in growing SMCs. Gal FP increased serum-induced DNA synthesis of human SMCs on plastic or endogenous ECM, but not of a rat PAC1 SM cell line. Also, Gal FP slightly increased SMC adhesion to ECM. SMCs exhibited a complex pattern of receptor-ligand interactions with Gal FP. The Gal-1 binding to SMCs was much stronger than to ECM, produced by these SMCs. We identified new ECM proteins: thrombospondin, vitronectin and osteopontin, which bound to Gal FP in a dose- and beta-galactoside-dependent manner in ELISA. CONCLUSIONS: Gal-1 binding to SMCs was stronger than to ECM, although ECM of atherosclerotic blood vessels contained additional ECM proteins which bound to Gal-1. Gal-1 was upregulated during SMC growth and Gal FP enhanced serum-induced DNA synthesis in SMCs. Overall, Gal-1 upregulation is likely to provide a reinforcement of serum-induced events during vascular injury.

Inhibition of vascular smooth muscle cell adhesion and migration by c7E3 Fab (abciximab): a possible mechanism for influencing restenosis.

OBJECTIVES: Brief intravenous administration of chimeric antibody c7E3 Fab during coronary angioplasty has been shown in some studies to provide long term protection against coronary events. Smooth muscle cell (SMC) adhesion and migration are key initial steps in the development of restenosis. The purpose of this study was to investigate the effect of c7E3 Fab on adhesion and migration of SMC to the extracellular matrix (ECM) proteins osteopontin (Opn) and vitronectin (Vn). METHODS: Adhesion of human vascular SMCs to ECM proteins was quantified using a CyQUANT assay kit. Migration of SMCs to Vn, Opn and PDGF was studied using a modified Boyden's chamber migration assay. Integrin expression was determined by immunoprecipitation. RESULTS: c7E3 Fab reduced SMC adhesion on Vn and Opn to 69.2+/-3.3% (P<0.001) and 52.5+/-4.8% (P<0.001) respectively, compared to adhesion without antibody present. This reduction was the same as that for anti-alpha(v)beta(3) integrin antibody LM609 (P=0.5). The combination of anti-alpha(v)beta(5) integrin antibody and c7E3 Fab had a greater effect than either antibody alone (P<0.001). c7E3 Fab reduced SMC migration to Vn and Opn to 51.6+/-8.9% (P<0.001) and 20.3+/-6.1% (P<0.001) respectively, compared to migration in the absence of antibodies. Again, similar results were seen with LM609. PDGF-induced SMC migration was also inhibited by c7E3 Fab (P=0.004) and LM609 (P=0.001), but to much less an extent. The migration SMCs from a culture found not to express the alpha(v)beta(3) integrin was unaffected by these antibodies, strengthening the argument that c7E3 Fab inhibits SMC function via this integrin. CONCLUSIONS: c7E3 Fab inhibits the adhesion and migration of SMCs via the alpha(v)beta(3) integrin. The inhibition, however, is partial, and varied depending on type of ECM protein and alpha(v)beta(3) integrin expression. Some of the clinical benefits of c7E3 Fab may be due to its effect on SMCs.

Antitumour activity of cytotoxic liposomes equipped with selectin ligand SiaLe(X), in a mouse mammary adenocarcinoma model.

The overexpression of lectins by malignant cells compared with normal ones can be used for the targeting of drug-loaded liposomes to tumours with the help of specific carbohydrate ligands (vectors). Recently we have shown that liposomes bearing specific lipid-anchored glycoconjugates on a polymeric matrix bind in vitro to human malignant cells more effectively and, being loaded with a lipophilic prodrug of merphalan, reveal higher cytotoxic activity compared with unvectored liposomes. In this study, carbohydrate-equipped cytotoxic liposomes were tested in vivo in a mouse breast cancer model, BLRB-Rb (8.17)1Iem strain with a high incidence of spontaneous mammary adenocarcinoma (SMA). Firstly, a cell line of the SMA was established which was then used to determine the specificity of the tumour cell lectins. After screening of the lectin specificity of a number of fluorescent carbohydrate probes, SiaLe(X) was shown to be the ligand with the most affinity, and a lipophilic vector bearing this saccharide was synthesised. Then different liposomal formulations of the synthetic merphalan lipid derivative and SiaLe(X) vector were prepared and applied in the treatment of mice with grafted adenocarcinomas. The results of the tumorigenesis data show that the therapeutic efficacy of merphalan increases sharply after its insertion as a lipophilic prodrug into the membrane of SiaLe(X)-vectored liposomes.