The Experts below are selected from a list of 150 Experts worldwide ranked by ideXlab platform

Ichiro Azuma - One of the best experts on this subject based on the ideXlab platform.

  • mdp lys l18 a synthetic muramyl Dipeptide Derivative enhances antitumor activity of an inactivated tumor vaccine
    Journal of Microbiology and Biotechnology, 2000
    Co-Authors: Yung Choon Yoo, Seungyong Park, Kyungbok Lee, Ichiro Azuma
    Abstract:

    The adjuvant effect of a muramyl Dipeptide (MDP) Derivative, MDP-Lys (L18), on enhancing of antitumor immunity induced by X-irradiated tumor cells against highly metastatic B16-BL6 melanoma cells was examined in mice. Mice immunized intradermally (i.d.) with a mixture of X-irradiated B16-BL6 cells and MDP-Lys (L18) [Vac+MDP-Lys (L18)] followed by an intravenous (i.v.) inoculation of 10 4 viable tumor cells 7 days after immunization, showed a significant inhibition of experimental lung metastasis of B 16-BL6 melanoma cells. The most effective immunization for the prophylactic inhibition of tumor metastasis was obtained from the mixture of 100 μg of MDP-Lys (L18) and 10 4 X-irradiatied tumor vaccine. Furthermore, immunization of mice with Vac+MDP-Lys (L18), 3 days after tumor challenge, resulted in a significant inhibition of lung metastasis of B16-BL6 melanoma cells in an experimental lung metastasis model. Similarly, the administration of Vac+MDP-Lys (L18), 1 or 7 days after tumor removal, markedly inhibited tumor metastasis of B16-BL6 in a spontaneous lung metastasis model. When Vac+MDP-Lys (L18) was i.d. administered 3 days after subcutaneous (s.c.) inoculation of tumor cells (5 × 10 5 /site) on the back, mice treated with Vac+MDP-Lys (L18) showed inhibition of significantly tumor growth on day 20. These results suggest that MDP-Lys (L18) is able to enhance antitumor activity induced by X-irradiated tumor vaccine to reduce lung metastasis of tumor cells, and is a potent immunomodulating agent which may be applied prophylactically as well as therapeutically to treatment of cancer metastasis.

  • romurtide a synthetic muramyl Dipeptide Derivative promotes megakaryocytopoiesis through stimulation of cytokine production in nonhuman primates with myelosuppression
    Vaccine, 1997
    Co-Authors: Kenji Namba, Hironobu Nitanai, Tsuyoshi Otani, Eiko Yamamura, Ichiro Azuma
    Abstract:

    The response of megakaryocytes and cytokines to the administration of romurtide, a synthetic muramyl Dipeptide Derivative, was investigated in monkeys with myelosuppression by carboplatin-treatment. Romurtide increased the number of megakaryocytes and promoted the shift of megakaryocytes towards high ploidy class indicative of the promotion of the proliferation and maturation of megakaryocytes. The serum levels of interleukin-6, stem cell factor, and erythropoietin elevated significantly before the enhanced response of megakaryocytes induced by romurtide was observed. Romurtide also enhanced production of colony-stimulating factors (CSFs), such as granulocyte-CSF, macrophage-CSF, and granulocyte-macrophage CSF by monkey mononuclear cells. The stimulating effect of romurtide on the production of those cytokines and CSFs is likely to be responsible for the subsequent promotion of the proliferation and maturation of marrow megakaryocytes.

  • romurtide a synthetic muramyl Dipeptide Derivative accelerates peripheral platelet recovery in nonhuman primate chemotherapy model
    Vaccine, 1996
    Co-Authors: Kenji Namba, Hironobu Nitanai, Tsuyoshi Otani, Ichiro Azuma
    Abstract:

    We investigated the therapeutic effects of romurtide, a synthetic muramyl Dipeptide Derivative, on experimental thrombocytopenia induced by carboplatin in cynomolgus monkeys. A prolonged thrombocytopenia due to a severe myelosuppression was induced by carboplatin. Romurtide given subcutaneously elevated significantly the peripheral platelet counts during both early initiation and later recovery phase of thrombocytopenia, thereby shortening the time required for recovery to a normal platelet level and the duration of thrombocytopenia. An oral administration of romurtide was also found to have a similar therapeutic efficacy to subcutaneous administration. These results demonstrated a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

  • oral application of romurtide a synthetic muramyl Dipeptide Derivative stimulates nonspecific resistance to microbial infections and hematopoiesis in mice
    Vaccine, 1996
    Co-Authors: Kenji Namba, Tsuyoshi Otani, Ryohei Nakajima, Ichiro Azuma
    Abstract:

    Romurtide given orally enhanced the nonspecific resistance against microbial infections and hematopoiesis up to the levels achieved by subcutaneous (s.c.) injection of the compound in mice. Oral romurtide conferred protection and, in consequence, enhanced therapeutic efficacy of antibiotics against systemic infections in mice. The leukocytosis followed by the elevations of colony stimulating activity in serum and the colony forming unit of granulocyte-macrophage (c.f.u.-GM) in femoral bone marrow was observed as successive event in mice treated orally with romurtide. To obtain a comparable potency to s.c. injection of the compound at a dose of 0.1 mg per mouse, oral application required doses of 3 and 10 mg per mouse for stimulating the nonspecific resistance to infection and hematopoiesis, respectively.

  • b30 mdp a synthetic muramyl Dipeptide Derivative for tumour vaccination to enhance antitumour immunity and antimetastatic effect in mice
    Vaccine, 1992
    Co-Authors: Yung Choon Yoo, Ikuo Saiki, Katsuaki Sato, Ichiro Azuma
    Abstract:

    The effect of a muramyl Dipeptide Derivative (B30-MDP) on the augmentation of antitumour immunity against highly metastatic L5178Y-ML25 mouse lymphoma cells was examined in CDF1 (Balb/c x DBA/2) mice. Mice immunized with a mixture of X-irradiated tumour cells (10(3)) and B30-MDP (100 micrograms) on 7 days prior to challenge by viable tumour cells displayed a significant decrease in metastasis towards the target organs, liver and spleen, compared with that of untreated mice. Immunization of mice with the mixture on day 5 or 7 after tumour challenge, when the level of glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in sera of mice inoculated with viable tumour cells was observed to be normal, caused less metastasis than immunization with X-irradiated tumour cells alone. Sensitization with X-irradiated tumour cells admixed with B30-MDP induced almost two times higher cytotoxicity of spleen cells against L5178Y-ML25 lymphoma cells than sensitization with X-irradiated tumour cells without B30-MDP. In contrast, cytotoxic activity of spleen cells against another target, L1210 lymphoma cells derived from BDF1 mice, was not observed by immunization with X-irradiated L5178Y-ML25 cells with or without B30-MDP. Specific lysis by splenic cells of the immunized mice against L5178Y-ML25 cells decreased to the normal level when T cells were deleted from the immunized spleen cells by the treatment of rabbit anti-mouse Thy1.2 antibody and rabbit complement. These results indicate that B30-MDP is able to augment a specific tumour immunity due to the enhancement of cytotoxicity mediated by T lymphocytes, and is useful as an immunopotentiating agent for active immunization of inactivated tumour cells.

Alexandru C Stan - One of the best experts on this subject based on the ideXlab platform.

  • u373 mg cells express pept2 and accumulate the fluorescently tagged Dipeptide Derivative β ala lys nɛ amca
    Neuroscience Letters, 2010
    Co-Authors: Mathias Zimmermann, Kai Kappert, Alexandru C Stan
    Abstract:

    Abstract Aim of this study was to examine the Dipeptide transport of β-Ala-Lys-Nɛ-AMCA in the human glioma cell line U373-MG and its potential regulation by diverse hormones and culture media. A mixed glial primary cell culture of the newborn rat served as reference cell system. β-Ala-Lys-Nɛ-AMCA (β-Ala-Lys-Nɛ-7-amino-4-methyl-coumarin-3-acetic acid) is a highly specific reporter substrate to investigate the Dipeptide transport system PepT2. We were able to demonstrate that U373-MG cells express PepT2-mRNA and translocate β-Ala-Lys-Nɛ-AMCA via PepT2 into the cytoplasm. Previous results demonstrated that β-Ala-Lys-Nɛ-AMCA specifically accumulates in differentiated and dedifferentiated astrocytes but neither in differentiated nor dedifferentiated oligodendrocytes and in neurons. U373-MG cells were incubated with estradiol, testosterone, thyronine, dexamethasone, dibutyryl cyclic adenosine monophosphate and tetradecanoylphorbol acetate in order to detect potential substance-dependent changes in Dipeptide uptake. There was no significant increase or decrease of β-Ala-Lys-Nɛ-AMCA-uptake after stimulation. Northern blot analyses confirmed that PepT2-mRNA is expressed in U373-MG and glial cells but showed no regulation of PepT2-mRNA expression in both cell types. Future investigations might offer the opportunity of an anti-tumor therapy with cytotoxic agents linked to a Dipeptide-Derivative such as β-Ala-Lys.

  • pept2 transporter protein expression in human neoplastic glial cells and mediation of fluorescently tagged Dipeptide Derivative beta ala lys nepsilon 7 amino 4 methyl coumarin 3 acetic acid accumulation
    Journal of Neurosurgery, 2010
    Co-Authors: Mathias Zimmermann, Alexandru C Stan
    Abstract:

    Object The present study was aimed at analyzing the accumulation of the fluorescently tagged Dipeptide Derivative, β-Ala-Lys-Ne-7-amino-4-methyl coumarin-3-acetic acid (AMCA), in primary cultures of human neoplastic glial cells. This molecule is a highly specific reporter used to investigate the Dipeptide transport system hPepT2. Methods In this study the authors used immunocytochemical methods to determine the cell-specific accumulation of a small and fluorescently tagged reporter molecule named β-Ala-Lys-Ne-AMCA to detect Dipeptide transport capacity of neoplastic glial cells. Furthermore, specific mRNA levels were quantified using Northern blot analysis and the tissue distribution of hPepT2 mRNA transcripts was demonstrated with in-situ hybridization histochemical analysis. Results Recent fluorescent immunocytochemical analyses have revealed that β-Ala-Lys-Ne-AMCA specifically accumulates within anaplastic cells of astrocytic lineage but not in anaplastic oligodendrocytes or neurons. Northern blot anal...

Mark Krystal - One of the best experts on this subject based on the ideXlab platform.

  • design synthesis and pharmacokinetic evaluation of phosphate and amino acid ester prodrugs for improving the oral bioavailability of the hiv 1 protease inhibitor atazanavir
    Journal of Medicinal Chemistry, 2019
    Co-Authors: Murugaiah A. M. Subbaiah, Sandhya Mandlekar, Sridhar Desikan, Thangeswaran Ramar, Lakshumanan Subramani, Mathiazhagan Annadurai, Salil D. Desai, Sarmistha Sinha, Susan Jenkins, Mark Krystal
    Abstract:

    Phosphate and amino acid prodrugs of the HIV-1 protease inhibitor (PI) atazanavir (1) were prepared and evaluated to address solubility and absorption limitations. While the phosphate prodrug failed to release 1 in rats, the introduction of a methylene spacer facilitated prodrug activation, but parent exposure was lower than that following direct administration of 1. Val amino acid and Val-Val Dipeptides imparted low plasma exposure of the parent, although the exposure of the prodrugs was high, reflecting good absorption. Screening of additional amino acids resulted in the identification of an l-Phe ester that offered an improved exposure of 1 and reduced levels of the circulating prodrug. Further molecular editing focusing on the linker design culminated in the discovery of the self-immolative l-Phe-Sar Dipeptide Derivative 74 that gave four-fold improved AUC and eight-fold higher Ctrough values of 1 compared with oral administration of the drug itself, demonstrating a successful prodrug approach to the ...

Kenji Namba - One of the best experts on this subject based on the ideXlab platform.

  • romurtide a synthetic muramyl Dipeptide Derivative promotes megakaryocytopoiesis through stimulation of cytokine production in nonhuman primates with myelosuppression
    Vaccine, 1997
    Co-Authors: Kenji Namba, Hironobu Nitanai, Tsuyoshi Otani, Eiko Yamamura, Ichiro Azuma
    Abstract:

    The response of megakaryocytes and cytokines to the administration of romurtide, a synthetic muramyl Dipeptide Derivative, was investigated in monkeys with myelosuppression by carboplatin-treatment. Romurtide increased the number of megakaryocytes and promoted the shift of megakaryocytes towards high ploidy class indicative of the promotion of the proliferation and maturation of megakaryocytes. The serum levels of interleukin-6, stem cell factor, and erythropoietin elevated significantly before the enhanced response of megakaryocytes induced by romurtide was observed. Romurtide also enhanced production of colony-stimulating factors (CSFs), such as granulocyte-CSF, macrophage-CSF, and granulocyte-macrophage CSF by monkey mononuclear cells. The stimulating effect of romurtide on the production of those cytokines and CSFs is likely to be responsible for the subsequent promotion of the proliferation and maturation of marrow megakaryocytes.

  • romurtide a synthetic muramyl Dipeptide Derivative accelerates peripheral platelet recovery in nonhuman primate chemotherapy model
    Vaccine, 1996
    Co-Authors: Kenji Namba, Hironobu Nitanai, Tsuyoshi Otani, Ichiro Azuma
    Abstract:

    We investigated the therapeutic effects of romurtide, a synthetic muramyl Dipeptide Derivative, on experimental thrombocytopenia induced by carboplatin in cynomolgus monkeys. A prolonged thrombocytopenia due to a severe myelosuppression was induced by carboplatin. Romurtide given subcutaneously elevated significantly the peripheral platelet counts during both early initiation and later recovery phase of thrombocytopenia, thereby shortening the time required for recovery to a normal platelet level and the duration of thrombocytopenia. An oral administration of romurtide was also found to have a similar therapeutic efficacy to subcutaneous administration. These results demonstrated a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

  • oral application of romurtide a synthetic muramyl Dipeptide Derivative stimulates nonspecific resistance to microbial infections and hematopoiesis in mice
    Vaccine, 1996
    Co-Authors: Kenji Namba, Tsuyoshi Otani, Ryohei Nakajima, Ichiro Azuma
    Abstract:

    Romurtide given orally enhanced the nonspecific resistance against microbial infections and hematopoiesis up to the levels achieved by subcutaneous (s.c.) injection of the compound in mice. Oral romurtide conferred protection and, in consequence, enhanced therapeutic efficacy of antibiotics against systemic infections in mice. The leukocytosis followed by the elevations of colony stimulating activity in serum and the colony forming unit of granulocyte-macrophage (c.f.u.-GM) in femoral bone marrow was observed as successive event in mice treated orally with romurtide. To obtain a comparable potency to s.c. injection of the compound at a dose of 0.1 mg per mouse, oral application required doses of 3 and 10 mg per mouse for stimulating the nonspecific resistance to infection and hematopoiesis, respectively.

  • enhancement of platelet recovery in x irradiated guinea pigs by romurtide a synthetic muramyl Dipeptide Derivative
    Blood, 1994
    Co-Authors: Kenji Namba, Tsuyoshi Otani, Yasuaki Osada
    Abstract:

    The response of megakaryocytes and platelets to the administration of romurtide, a synthetic muramyl Dipeptide Derivative, was investigated in normal and irradiated guinea pigs. Romurtide was administered subcutaneously in a single dose or daily doses at levels of 1 to 100 micrograms/animal/day to normal animals to assess the dose response. Subsequently, dosage at 100 micrograms/animal/d for 8 consecutive days was initiated in separate groups of animals immediately after 1 Gy total body x-irradiation. In normal animals, a significant dose- dependent increase in the platelet count was noted, and a prolonged thrombocytopoiesis was detectable from 7 through 15 days after the initiation of romurtide administered for 8 days at a dose of 100 micrograms/animal/d. A significant increase in the white blood cell (WBC) count was also observed during days 1 through 11 after beginning romurtide treatment. In the irradiated animals, the treatment with romurtide increased platelet counts during the recovery phase of thrombocytopenia, thus apparently decreasing the time required for recovery to a normal platelet level. Before the rapid recovery of platelet counts by romurtide treatment, a marked increase in the number of megakaryocytes was noted as early as 7 days after irradiation. This increase was accompanied by an accelerated shift of the size distribution of megakaryocytes toward larger size class. Thus, the mean megakaryocyte size was significantly greater in guinea pigs receiving romurtide than in controls. Preceding the increase in the number of megakaryocytes, the serum interleukin-6 levels were found to be approximately 5 times greater than those in control animals. Treatment with romurtide diminished the WBC count nadir, resulting in significantly higher WBC count levels than in controls. Elevation of the plasma fibrinogen level was observed in the treated animals, and normalized gradually after discontinuation of romurtide treatment. These results indicate a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

Mathias Zimmermann - One of the best experts on this subject based on the ideXlab platform.

  • u373 mg cells express pept2 and accumulate the fluorescently tagged Dipeptide Derivative β ala lys nɛ amca
    Neuroscience Letters, 2010
    Co-Authors: Mathias Zimmermann, Kai Kappert, Alexandru C Stan
    Abstract:

    Abstract Aim of this study was to examine the Dipeptide transport of β-Ala-Lys-Nɛ-AMCA in the human glioma cell line U373-MG and its potential regulation by diverse hormones and culture media. A mixed glial primary cell culture of the newborn rat served as reference cell system. β-Ala-Lys-Nɛ-AMCA (β-Ala-Lys-Nɛ-7-amino-4-methyl-coumarin-3-acetic acid) is a highly specific reporter substrate to investigate the Dipeptide transport system PepT2. We were able to demonstrate that U373-MG cells express PepT2-mRNA and translocate β-Ala-Lys-Nɛ-AMCA via PepT2 into the cytoplasm. Previous results demonstrated that β-Ala-Lys-Nɛ-AMCA specifically accumulates in differentiated and dedifferentiated astrocytes but neither in differentiated nor dedifferentiated oligodendrocytes and in neurons. U373-MG cells were incubated with estradiol, testosterone, thyronine, dexamethasone, dibutyryl cyclic adenosine monophosphate and tetradecanoylphorbol acetate in order to detect potential substance-dependent changes in Dipeptide uptake. There was no significant increase or decrease of β-Ala-Lys-Nɛ-AMCA-uptake after stimulation. Northern blot analyses confirmed that PepT2-mRNA is expressed in U373-MG and glial cells but showed no regulation of PepT2-mRNA expression in both cell types. Future investigations might offer the opportunity of an anti-tumor therapy with cytotoxic agents linked to a Dipeptide-Derivative such as β-Ala-Lys.

  • pept2 transporter protein expression in human neoplastic glial cells and mediation of fluorescently tagged Dipeptide Derivative beta ala lys nepsilon 7 amino 4 methyl coumarin 3 acetic acid accumulation
    Journal of Neurosurgery, 2010
    Co-Authors: Mathias Zimmermann, Alexandru C Stan
    Abstract:

    Object The present study was aimed at analyzing the accumulation of the fluorescently tagged Dipeptide Derivative, β-Ala-Lys-Ne-7-amino-4-methyl coumarin-3-acetic acid (AMCA), in primary cultures of human neoplastic glial cells. This molecule is a highly specific reporter used to investigate the Dipeptide transport system hPepT2. Methods In this study the authors used immunocytochemical methods to determine the cell-specific accumulation of a small and fluorescently tagged reporter molecule named β-Ala-Lys-Ne-AMCA to detect Dipeptide transport capacity of neoplastic glial cells. Furthermore, specific mRNA levels were quantified using Northern blot analysis and the tissue distribution of hPepT2 mRNA transcripts was demonstrated with in-situ hybridization histochemical analysis. Results Recent fluorescent immunocytochemical analyses have revealed that β-Ala-Lys-Ne-AMCA specifically accumulates within anaplastic cells of astrocytic lineage but not in anaplastic oligodendrocytes or neurons. Northern blot anal...