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M Reinis

Publications and source records attributed to M Reinis.

12 recordsLinked to original sources
PubMed2001

Therapy of HPV 16-associated carcinoma with dendritic cell-based vaccines: in vitro priming of the effector cell responses by DC pulsed with tumour lysates and synthetic RAHYNIVTF peptide.

Murine carcinoma induced by MK 16 cells expressing HPV 16 E6/E7 oncogenes was utilized to examine the therapeutic effect of dendritic cell-based tumour vaccines. Mice carrying 5-day MK 16 tumours were injected peritumorally with either dendritic cells (DC) or DC pulsed with MK 16 tumour lysate. Both the unpulsed and MK 16 lysate-pulsed DC vaccines inhibited growth of the MK 16 transplants, the pulsed DC being more efficient than the unpulsed vaccines. In vitro priming of the effector cell-mediated anti-MK 16 responses by DC pulsed with MK 16 tumour lysate and a synthetic HPV 16 E7(49-57) peptide RAHYNIVTF was compared. The priming activity of the lysate was substantially higher than that of the HPV 16 E7(49-57) peptide; the priming activity was similar to that of a standard moderately immunogenic chemically-induced sarcoma. Taken collectively, these results suggest that DC vaccines pulsed with HPV 16-associated tumour lysates represent a prospective modality for treatment of HPV 16-associated carcinomas.

Amino Acid Sequence↗
PubMed2000

Irradiation of genetically modified plasmacytoma vaccines results in upregulation of CD80 molecule expression, IL-2 production and higher therapeutic efficacy of the vaccines.

It has been found previously that irradiated, IL-2 gene-modified plasmacytoma (X63-m-IL-2) vaccines are more efficient in the therapy of the parental (X63-Ag8.653) plasmacytoma than live plasmacytoma vaccines. In this communication, we have demonstrated that irradiation of murine IL-2-producing plasmacytoma vaccines resulted in upregulation of CD80 molecule expression and IL-2 production. The expression of MHC class I antigens was not altered. The upregulation of the CD80 membrane molecule expression in X63-m-IL-2 cells was higher after irradiation with 150 Gy than after irradiation with 50 Gy. Comparable upregulation of the CD80 molecule expression has also been demonstrated after irradiation of the parental murine X63-Ag8.653 plasmacytoma cells. The results indicate that upregulation of the CD80 molecule expression and enhanced IL-2 production in irradiated X63-m-IL-2 cells was responsible for the higher therapeutic effectiveness of the irradiated plasmacytoma vaccine.

Animals↗
PubMed2000

Peritumoral administration of antigen-unstimulated bone marrow-derived dendritic cells inhibits tumour growth.

Murine BM cells from B6 mice were grown in vitro in medium supplemented with GM-CSF and IL-4 to differentiate DC from DC precursors. After 10 days of culture, approximately 20% of the cell population exhibited the characteristic morphology of BMDC. In cytofluorometric analysis the morphological changes of cells were accompanied by upregulation of the expression of the MHC class II, CD11c, CD80, and CD86 molecules. The BMDC were pulsed with a lysate of syngeneic MK16 carcinoma cells and used for in vitro activation of SC. Co-cultivation of the carcinoma lysate-pulsed BMDC with SC induced a proliferative response of the syngeneic SC. Priming of the proliferative responses was more efficient when the BMDC were grown in the presence of GM-CSF and IL-4 for 10 days than for 7 days. The in vivo effect of mature, tumour lysate-unstimulated BMDC was examined in mice carrying syngeneic MK16 carcinoma transplants. It has been found that local pretreatment with BMDC inhibits growth of a subsequent challenge inoculum of the MK16 cells. Similarly, treatment of mice carrying small MK16 tumours and of those with MK16 surgical minimal residual disease performed with BMDC significantly inhibited tumour growth. It can be concluded from these results that local concentration of mature BMDC at the tumour site can control the development and growth of the transplanted tumour inoculum.

Animals↗
PubMed1999

[Molecular biology and serologic analysis in an epidemic of viral hepatitis B in vaccinated patients on hemodialysis].

The authors analyzed an epidemic of viral hepatitis B during which 43% patients of the hemodialyzation centre in K were infected. Using the method of sequence analysis of the DNA of hepatitis B virus they identified the source of infection. They monitored serologically the course of infection in all infected subjects and the state of specific antibody immunity in patients and staff. 22% infections were manifested clinically and 75% infected HBsAg positive patients developed chronic hepatitis. Although 38 of 42 hemodialyzed patients were vaccinated against hepatitis B, 20 patients lacked anti-HBs antibodies before the epidemic. Only one of the patients without anti-HBs was not infected. In 10 immune patients the rise of antibody levels confirmed that they were also exposed to HBV. The effectiveness of vaccination against VHB in hemodialyzed patients is markedly lower. Vaccination of these patients is an important but only supplementary provision in VHB prevention. Sequence analysis of HBV DNA may be a useful tool of epidemiological analysis.

Cross Infection↗
PubMed1999

Interleukin 2 gene therapy of surgical minimal residual tumour disease: characterization of cytolytic effector cells from tumour progressors and regressors.

Experiments were designed to characterize cytolytic effector cells from mice with SMRTD treated with IL-2 gene therapy. Mice were inoculated with syngeneic murine MK16 carcinoma cells. When the tumours reached 8-12 mm in diameter, they were excised and the operated mice were randomized into two groups. The first group without any further treatment was designated as operated-only; the second group, vaccinated 3 days after the operation with IL-2-producing tumour vaccine, is referred to as operated-vaccinated. Tumour recurrence rate in the operated-only mice was 90 percent; in the operated-vaccinated group the recurrence rate was 38.5 percent (progressors). The remaining 61.5 percent of mice were permanently protected (regressors). On day 53, the tumour progressors, regressors and healthy controls were sacrificed, and their spleen cells were used for 51Cr microcytotoxicity assay. Splenocytes from any group of mice were not cytolytic when allowed to react with MK16, YAC-1 (NK sensitive) and C1498 (NK resistant) targets. However, when grown for 3 days in IL-2-containing medium, the splenocytes from all groups of mice could develop cytolytic activity. The cytolytic activity of splenocytes from tumour progressors and regressors was substantially lower then that of splenocytes from healthy controls. In addition, significantly lower cytolytic activity was observed with IL-2-activated splenocytes from tumour progressors as compared to that of tumour regressors. Depletion of NK1.1+ cells or CD4+ plus CD8+ cells prevented the induction of significant IL-2-stimulated cytotoxicity directed against MK16 and C1498 targets in spleen cell cultures from tumour progressors, regressors, and healthy control mice, indicating that both, NK1.1+ and CD4+ plus CD8+, cells participate in the antitumour effect of IL-2 gene therapy. This was further supported by the finding that after depletion of CD4+ plus CD8+ cells, a residual cytolytic activity directed exclusively against NK-sensitive YAC-1 cells was observed.

Animals↗
PubMed1998

CD38 functions are regulated through an internalization step.

The endocytosis of the human CD38 molecule has been investigated in normal lymphocytes and in a number of leukemia- and lymphoma-derived cell lines. CD38 internalization was followed using radioiodinated Abs in an acidic elution endocytosis assay to monitor the effects of cross-linking on internalization processes and to quantify the ratio of the internalized molecule. Second, conventional, confocal, and electron microscopies were used to evaluate the morphologic effects induced by ligation of the molecule with Abs mimicking the natural ligand(s). The results demonstrated that internalization is a reproducible phenomenon following CD38 ligation with both agonistic and nonagonistic specific Abs and involving only a fraction of the entire amount of the surface molecule. It is independent from signal transduction as can be inferred by the observation that 1) both agonistic and non agonistic Abs are effective and 2) the dynamic of internalization is much slower than that of cellular signaling. Morphologic studies demonstrated that endocytosis induced as a result of CD38 ligation presents a very specific pathway consisting of subcellular organelles fundamental to the processing of the complex. Our data indicate that down-regulation by endocytosis may be, in parallel with shedding, a regulatory element in activation and adhesion processes mediated by CD38. However, internalization seems not to be a key step in triggering intracellular signaling; more likely, it is a negative feedback control mechanism which interrupts signal transduction or cell-cell cross-talks mediated by membrane CD38.

ADP-ribosyl Cyclase↗
PubMed1993

Receptor-mediated transport of oligodeoxynucleotides into hepatic cells.

Receptor-mediated endocytosis was employed for a highly efficient transport of oligodeoxynucleotides into hepatoma cell line PLC/PRF/5. The oligodeoxynucleotides were bound to the asialofetuin-poly-L-lysine conjugate and this complex was internalized by the cells via asialoglycoprotein receptor, an endocytic receptor unique for hepatocytes. Binding of the oligodeoxynucleotides to the complex dramatically increased their cellular uptake more than 20-fold. Chloroquine, a lysosomatropic agent, further increased the transport of the complex but not of the free oligodeoxynucleotides.

Asialoglycoprotein Receptor↗
PubMed1993

Inhibition of hepatitis B virus surface gene expression by antisense oligodeoxynucleotides in a human hepatoma cell line.

We have studied the inhibitory effect of antisense oligodeoxynucleotides on the expression of hepatitis B virus surface antigens. Human hepatoma cell line PLC/PRF/5 harbors several integrated copies of the HBV genome and produces and secretes hepatitis B virus surface antigen (HBsAg) to the medium. Synthetic antisense oligodeoxynucleotides complementary to various regions of the surface antigen gene were synthesized and their ability to block its expression was tested. Oligodeoxynucleotides (17- and 21-mers) complementary to regions covering ATG codons of both preS2 and S genes significantly inhibited preS2 and S protein production. Less efficient inhibition was achieved when the oligonucleotide complementary to the inside S gene region was assayed.

Base Sequence↗
PubMed1989

Expression of hepatitis B virus large envelope protein in Escherichia coli and Saccharomyces cerevisiae.

The gene coding for hepatitis B large envelope protein was cloned under the lac promoter in bacterial vector pUC-8 and under the ADH1 promoter in yeast expression shuttle vector pVT103-U, and expression of HBsAg in bacteria and yeast was determined. The strongest expression of large envelope protein was obtained after transformation of the protease-deficient yeast strain BJ1991. The recombinant large envelope protein did not form complex 22-nm particles and was not secreted into medium.

Cloning, Molecular↗
PubMed1984

Vascular invasion in Stage I carcinoma of the cervix.

Vascular invasion was identified as an important prognostic variable for all lesion sizes in 138 patients with Stage I cervical carcinoma. A matched pairs analysis, controlling for lesion size and extracervical spread, showed that vascular invasion was significantly associated with poor outcome. Regression analysis also indicated that vascular invasion contributed prognostic information beyond that available from lesion size and extracervical spread. Studies of adjunctive therapy based on the prognostic variables are recommended.

Carcinoma↗
PubMedDate not supplied

Functional associations of CD38 with CD3 on the T-cell membrane.

CD38 is a multifunctional membrane surface glycoprotein expressed by different cells and tissues, including T cells at certain stages of their development. Besides its involvement in transmembrane signaling, CD38 play a role in cell adhesion processes. Structurally, membrane CD38 was reported as presenting lateral associations with molecules involved in recognition and signaling, namely with the TCR/CD3 complex in T cells. Here we report that ligation of CD38 by agonistic and non-agonistic monoclonal antibodies exerts different effects on T cells, the former inducing down-modulation of the associated molecules, probably through a protein kinase C-dependent mechanism. This observation supports the view that the reduced expression of TCR/CD3 is secondary to interplay with CD38-mediated signaling, which partially overlaps with the CD3-mediated pathway. CD3 ligation by monoclonal antibodies leads not only to the expected internalization of the TCR/CD3 complex but also to down-modulation of surface CD38. The results obtained indicate that CD38 is closely associated with the CD3/TCR complex and that co-modulation of CD38 with TCR/CD3 is a critical step in signaling processes on T lymphocytes.

ADP-ribosyl Cyclase↗