scholarly journals Therapeutic Effect of Clarithromycin on a Transplanted Tumor in Rats

1999 ◽  
Vol 43 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Kazuhiko Sassa ◽  
Yutaka Mizushima ◽  
Takashi Fujishita ◽  
Rokuo Oosaki ◽  
Masashi Kobayashi
Keyword(s):  
Body Weight ◽  
Tumor Cells ◽  
Death Rate ◽  
Antitumor Effect ◽  
Transforming Growth Factor ◽  
Mammary Adenocarcinoma ◽  
Spleen Cells ◽  
Therapeutic Antitumor Effect ◽  
Allogeneic Tumor

ABSTRACT The therapeutic antitumor effect of clarithromycin (CAM) was examined with the 13762NF mammary adenocarcinoma and F-344 rat system. When CAM treatment at a dosage of 2 mg/kg of body weight orally for 21 days was commenced after inoculation of the tumor, no significant decrease in death rate was observed, although the loss in body weight was less than that in the untreated group. When tumor-bearing (TB) rats were treated with CAM in combination with carboplatin or cyclophosphamide, a significant decrease in the death rate was obtained, although neither treatment alone proved to be effective. A beneficial effect was also observed when CAM treatment was combined with surgical treatment. CAM showed no direct cytotoxicity to this tumor in vitro according to the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Spleen cells obtained from TB rats receiving CAM treatment showed a stronger tumor-neutralizing activity than those from rats which had not received CAM treatment (Winn assay). Enhanced induction of cytotoxic cells to allogeneic tumor was also observed in rats immunized with allogeneic tumor cells together with CAM treatment (51Cr release assay). The 13762NF tumor produces transforming growth factor-β (TGF-β), tumor necrosis factor alpha, and matrix metalloproteinase-9, and treatment of tumor cells with CAM in vitro for 24 h significantly inhibited the expression of the genes coding for these proteins (reverse transcription-PCR). Levels of expression of the TGF-β and interleukin-6 genes of spleen cells obtained from CAM-treated TB rats were both significantly lower than those of spleen cells from CAM-untreated TB rats. This study suggests that CAM has biological response modifier activities resulting in a beneficial therapeutic antitumor effect and might be useful for the treatment of human cancers.

scholarly journals CELLS MEDIATING SPECIFIC IN VITRO CYTOTOXICITY

1971 ◽  
Vol 134 (6) ◽  
pp. 1385-1402 ◽  
Author(s):  
Pierre Golstein ◽  
Erik A. J. Svedmyr ◽  
Hans Wigzell
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
In Vitro Cytotoxicity ◽  
Specific Adsorption ◽  
Target Cells ◽  
Spleen Cells ◽  
Allogeneic Tumor ◽  
Specific Receptors ◽  
Gradient Fractionation

Spleen cells from mice immunized with allogeneic tumor cells are incubated on different fibroblast monolayers. The nonadsorbed cells are tested for cytotoxicity against 51Cr-labeled target cells. The cytotoxicity of nonadsorbed cells is much lower after incubation on fibroblasts syngeneic to the immunizing tumor cells than after incubation on fibroblasts syngeneic to the immune cells. This specific decrease of cytotoxic activity depends on the duration and temperature of incubation on monolayers. After incubation the monolayers are trypsinized and pure populations of adsorbed lymphocytes isolated by density gradient fractionation. The cytotoxicity of such trypsin-eluted, gradient-purified lymphocytes is much higher when these lymphocytes are isolated from fibroblasts syngeneic to the immunizing tumor cells than when they are isolated from fibroblasts syngeneic to the immune cells. These experiments demonstrate specific adsorption of immune cells onto fibroblasts carrying the immunizing antigens, and thus prove the existence of specific receptors at the surface of these immune cells. Spleen cells from mice immunized with two types of allogeneic tumor cells bearing different H-2 antigen alleles are incubated on different fibroblast monolayers. The results of such experiments show a differential specific adsorption pattern, suggesting independent adsorption of two populations of immune cells bearing receptors directed against either one or the other immunizing H-2 antigen. The existence of at least a majority of cells, each of which is homogeneous as to the specificity of its receptors, makes it likely that specific receptors are synthetized by the cells that bear them. The role of specific receptor-bearing cells in the killing process is discussed.

In Vitro Synergic Effect of Interferon Gamma Combined with Liposomes Containing Muramyl Tripeptide on Human Monocyte Cytotoxicity Against Fresh Allogeneic and Autologous Tumor Cells

1994 ◽  
Vol 80 (5) ◽  
pp. 385-391 ◽  
Author(s):  
Enzo Galligioni ◽  
Manuela Santarosa ◽  
Daniela Favaro ◽  
Antonella Spada ◽  
Renato Talamini ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Tumor Cells ◽  
Cultured Cells ◽  
Combined Treatment ◽  
Target Cells ◽  
Autologous Tumor ◽  
Synergic Effect ◽  
Recombinant Interferon ◽  
Allogeneic Tumor

Aims The purpose of the present study was to investigate whether human recombinant interferon- γ (hrIFN - γ) can act synergically with various activators in increasing the cytotoxicity of cancer patient monocytes against fresh autologous and allogeneic tumor cells. Methods Fresh target cells were obtained by means on the mechanical and enzymatic dissociation of human renal carcinomas. A 375 and SW 626 cell lines were used as positive controls. Monocytes from renal cancer patients and normal volunteers were activated in vitro with lipopolysaccharide, muramyl tripeptide (MTP-PE) or liposomes containing MTP-PE (MTP-PE liposomes), with or without a pre-incubation with hrIFN- γ and were tested for cytotoxicity by means of a 72-hr 111indium-release assay. All of the patients were tumor free at the time of the study. Results Cancer patient peripheral blood monocytes were activated in vitro by different immunomodulators and became cytotoxic to freshly dissociated autologous or allogeneic tumor cells. A synergic effect producing maximal cytotoxicity was obtained with an appropriately scheduled combination of hrIFN- γ (10 U/ml) and MTP-PE liposomes (50 nm/ml), free lipopolysaccharide (10 μg/ml) or MTP-PE (100 μg/ml). The synergic cytotoxicity was observed against fresh allogeneic and autologous tumor cells, as well as against cultured cells. Conclusions All of these data support the possibility of a combined treatment using hrIFN- γ and MTP-PE liposomes in human studies, particularly when it is borne in mind that liposomes can prevent the direct toxicity of many immunomodulators and that the low levels of hrIFN- γ required for the synergic activation are not toxic in vivo.

scholarly journals Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice

2011 ◽  
Vol 208 (12) ◽  
pp. 2489-2496 ◽  
Author(s):  
Uri Sela ◽  
Peter Olds ◽  
Andrew Park ◽  
Sarah J. Schlesinger ◽  
Ralph M. Steinman
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Graft Versus Host Disease ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Spleen Cells ◽  
Host Disease ◽  
Graft Versus Host ◽  
Naturally Occurring

Foxp3+ regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor β (TGF-β) and retinoic acid. We found that the CD11chigh dendritic cell fraction was the most potent at inducing high numbers of alloreactive Foxp3+ cells. The induced CD4+CD25+Foxp3+ cells appeared after extensive proliferation. When purified from the MLR, iT reg cells suppressed both primary and secondary MLR in vitro in an antigen-specific manner. After transfer into allogeneic mice, iT reg cells persisted for 6 mo and prevented graft versus host disease (GVHD) caused by co-transferred CD45RBhi T cells. Similar findings were made when iT reg cells were transferred after onset of GVHD. The CNS2 intronic sequence of the Foxp3 gene in the persisting iT reg cells was as demethylated as the corresponding sequence of naturally occurring T reg cells. These results indicate that induced Foxp3+ T reg cells, after proliferating and differentiating into antigen-specific suppressive T cells, can persist for long periods while suppressing a powerful inflammatory disease.

Preventive and therapeutic antitumor effect of tumor vaccine composed of CpG ODN class C and irradiated tumor cells is triggered through the APCs and activation of CTLs

Vaccine ◽  
2007 ◽  
Vol 25 (49) ◽  
pp. 8241-8256 ◽  
Author(s):  
Srdjan Novaković ◽  
Vida Stegel ◽  
Andreja Kopitar ◽  
Alojz Ihan ◽  
Barbara Jezeršek Novaković
Keyword(s):  
Tumor Cells ◽  
Antitumor Effect ◽  
Tumor Vaccine ◽  
Cpg Odn ◽  
Therapeutic Antitumor Effect ◽  
Class C

Cytokine-mediated antitumor effect of OK-432 on urinary bladder tumor cells in vitro

1997 ◽  
Vol 25 (4) ◽  
pp. 239-245 ◽  
Author(s):  
Shigeru Sakano ◽  
Tomoyuki Shimabukuro ◽  
Yasukazu Ohmoto ◽  
Katsusuke Naito
Keyword(s):  
Urinary Bladder ◽  
Tumor Cells ◽  
Bladder Tumor ◽  
Antitumor Effect ◽  
Urinary Bladder Tumor

scholarly journals Effect of thiazole derivative complexed with nanoscale polymeric carriers on cellular ultrastructure of murine lymphoma cells in vivo

2021 ◽  
Vol 15 (2) ◽  
pp. 15-24
Author(s):  
M. V. Popovych ◽  
◽  
Ya. R. Shalai ◽  
V. P. Hreniukh ◽  
O. R. Kulachkovskyy ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasma Membrane ◽  
Tumor Cells ◽  
The Body ◽  
Thiazole Derivatives ◽  
Lymphoma Cells ◽  
Thiazole Derivative ◽  
Polymeric Carriers

Background. A pronounced cytotoxic action of the thiazole derivatives complexed with polymeric carriers on tumor cells in vitro was reported earlier, while no cytotoxicity of these compounds was detected toward noncancerous cells. It was found that thiazole derivatives at concentrations of 10 and 50 µM affected lymphoma cell ultrastructure in vitro. The purpose of this work was to investigate the effect of thiazole derivative 8-methyl-2-Me-7-[trifluoromethyl-phenylmethyl]-pyrazolo-[4,3-e]-[1,3]- thiazolo-[3,2-a]-pyrimidin-4(2H)-one (PP2) and its complexes with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th12) and poly(PEGMA) (Th14) on the ultrastructure of lymphoma cells in vivo. Materials and Methods. Experiments were conducted on white wild-type male mice with grafted NK/Ly lymphoma. Ascite tumors were created by intreperitoneal inocu­lation of 1–2 mln of Nemet–Kelner lymphoma cells to mice. On the 12th day after inoculation, the body weight of animals was increased by 140–160 % mostly due to ascites growth. For treatment of ascites three solutions of the chemical compounds were prepared: PP2, PP2 + Th12, PP2 + Th14 and administered to the mice intraperitoneally for 5 days. The final concentration of PP2 was 5 mg/kg of body weight. Abdominal drainage from ascites was performed with a sterile syringe under chloroform anesthesia on the 10th day after the start of treatment. The ultrastructure of the cells was examined by electron microscopy. Results. Еlectron microscopy study showed that control lymphoma cells have a special subcellular formations such as a relatively large nucleus, and specific plasma membrane filaments. The effects of thiazole derivative revealed apoptotic and necrotic manifestations of cytotoxicity, such as a deformation and disintegration of nucleus, a decreased nucleus/cytoplasm ratio, a destruction of the plasma membrane and a change of mitochondria shape. The studied compound complexed with polymeric carriers caused an apoptotic-like changes in lymphoma cells. Under the action of such complexes, the nucleus/cytoplasm ratio decreased and the area of mitochondria increased. Conclusions. The obtained results suggest that the tested compounds induce apoptosis in tumor cells. Complexes of thiazole derivative with polymers do not impair the effect of the compound on lymphoma cells. The obtained data can be used to carry out further preclinical studies of thiazole derivatives complexed with polymeric carriers as potential antitumor drugs.

scholarly journals THE CYTOTOXIC EFFECT OF CHELIDONIUM MAJUS IN VITRO

2015 ◽  
Vol 8 (2) ◽  
Author(s):  
Vladimíra Tomečková ◽  
Veronika Tkáčová ◽  
Peter Urban ◽  
Marek Stupák
Keyword(s):  
Tumor Cells ◽  
Hela Cells ◽  
Antiproliferative Activity ◽  
Cytotoxic Effect ◽  
Lymphoblastic Leukemia ◽  
Mammary Adenocarcinoma ◽  
Chelidonium Majus ◽  
Mcf 7 ◽  
Lipophilic Substances

The effect of aqueous and ether Chelidonium majus haulms extract on cervical HeLa tumor cells, mammary adenocarcinoma MCF 7 tumor cells and acute lymphoblastic leukemia CEM tumor cells in vitro have been studied. The purpose of this research was to compare the effect of aqueous and ether Chelidonium majus haulms extract on selected tumor cells. Colorimetric MTT assay have been used for the study of the antiproliferative effect of aqueous and ether haulms extract of Chelidonium majus on cell viability in vitro. The results of the experiments have shown the cytotoxic effect of the aqueous and the ether Chelidonium majus haulms extract on the individual tumor cells. The aqueous Chelidonium majus haulms extract was the most effective on CEM cells, it was less effective on MCF 7 cells and it was the least effective on HeLa cells. The ether haulms extract of Chelidonium majus was the most effective at all of studied concentrations on CEM cells and MCF 7 cells in comparison with HeLa cells, where it was significantly effective only at the highest concentration. Aqueous and ether haulms extract of Chelidonium majus tested in vitro indicated their cytotoxic activity. Both haulms extract of Chelidonium majus were more efficient on CEM cells. It is assumed that higher antiproliferative activity of ether haulms extract of Chelidonium majus is the result of higher antiproliferative activity of lipophilic substances. The lipophilic substances pass through membrane and bind to various proteins and change their biological activity.

scholarly journals Differential Modulatory Effects of Clarithromycin on the Production of Cytokines by a Tumor

1999 ◽  
Vol 43 (11) ◽  
pp. 2787-2789 ◽  
Author(s):  
Kazuhiko Sassa ◽  
Yutaka Mizushima ◽  
Masashi Kobayashi
Keyword(s):  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Mammary Adenocarcinoma ◽  
Necrosis Factor Alpha ◽  
Adenocarcinoma Cells ◽  
The Matrix ◽  
Factor Alpha ◽  
Metalloproteinase 9

ABSTRACT In vitro treatment with clarithromycin inhibited the expression of the matrix metalloproteinase-9, transforming growth factor β, and tumor necrosis factor alpha genes in 13762NF rat mammary adenocarcinoma cells. Transient enhancement, rather than inhibition, was observed for the interleukin-6 gene, and no significant change was observed for the tissue inhibitor of metalloproteinase-2 gene. Such an effect was not observed for cefotiam or gentamicin.

scholarly journals Forskolin enhances the antitumor effect of oncolytic measles virus by promoting Rab27a dependent vesicular transport system in the lung cancer A549 cells in vitro

2020 ◽  
Author(s):  
Mao Xia ◽  
Yongquan Xia ◽  
Xuejing Xu ◽  
Gang Meng ◽  
Hong Yan ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Transport System ◽  
Measles Virus ◽  
Antitumor Effect ◽  
Vesicular Transport ◽  
A549 Cells ◽  
Over Expression ◽  
Combined Strategy

Abstract Background: Measles vaccine strain viruses (MV-Edm) are an ideal platform for developing safe and effective oncolytic vectors. However, despite the promising pre-clinical data, understanding of determinants of efficacy and, thus, the interplay of the oncolytic virus with particular agents remains limited.Methods: We investigated the potency of forskolin enhancing the antitumor effect of oncolytic measles virus by promoting Rab27a dependent vesicular transport system. Cells were infected with MV-Edm and the vesicles were observed by TEM. The oncolytic effects of MV-Edm/Forskolin were investigated in vitro. Results: Here we demonstrate that the MV-Edm infection and spread in tumor, which are indispensable processes for the viral oncolysis, depend on the vesicular transport system of tumor cells. On the contrary, the tumor cells display a responsive mechanism to restrain the MV-Edm spread by down-regulating the expression of Rab27a, which is a key member of the vesicle transport system. Over-expression of Rab27a promotes the oncolytic efficacy of MV-Edm towards A549 tumor cells. Finally, we find a Rab27a agonist Forskolin, is capable of promoting the oncolytic effect of MV-Edm in vitro. Conclusions: Our study reveals the important role of vesicle transporter Rab27a in the whole program of MV-Edm mediated oncolysis. We also provide a combined strategy of Forskolin and MV-Edm, which may exert a synergistic anti-tumor effect, for clinical treatment for patients with tumor.

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