Antitumor Activity of Liposomal Prednisolone Phosphate Depends on the Presence of Functional Tumor-Associated Macrophages in Tumor Tissue

Banciu, Manuela; Metselaar, Josbert M.; Schiffelers, Raymond M.; Storm, Gert

doi:10.1593/neo.07913

Cited by 88 publications

(75 citation statements)

References 42 publications

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“…In accordance with previous studies (4)(5)(6)19), the overall production of the majority of the inflammatory and angiogenic factors in C26 cells co-cultivated with peritoneal macrophages was 2-fold higher than the production of the same factors in C26 cells cultivated alone (Fig. 3).…”

Section: Effects On the Production Of Inflammatory/angiogenic Proteinsupporting

confidence: 92%

“…This method is based on the incorporation of the pyridine analog bromodeoxyuridine (BrdU), instead of thymidine, into the DNA of proliferating cells. C26 cells (1x10 4 /well), cultured alone or together with peritoneal macrophages at a density ratio of 1:4, were seeded into 96-well plates and incubated with different concentrations of 5-FU for 72 h. Cells incubated only with medium were used as controls. Subsequently, cells were incubated with BrdU solution for 24 h and the culture medium was completely removed from each well.…”

Section: Methodsmentioning

confidence: 99%

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Dual role of macrophages in the response of C26 colon carcinoma cells to 5-fluorouracil administration

et al. 2016

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Abstract. Previous studies have demonstrated that tumor-associated macrophages (TAMs) are pivotal players in tumor progression via modulation of tumor angiogenesis, inflammation, metastasis and oxidative stress, as well as of the response of cancer cells to cytotoxic drugs. Nevertheless, the role of TAMs in the prognosis of colorectal cancer remains controversial. Therefore, the present study aimed to investigate how TAMs mediate the response of C26 colon carcinoma cells to the cytotoxic drug 5-fluorouracil (5-FU), upon TAM co-cultivation with these cancer cells in vitro. In this respect, 5-FU cytotoxicity was assessed in C26 cells in standard culture and in a co-culture with peritoneal macrophages, the production of NF-κB was determined by western blot analysis, and the production of angiogenic/inflammatory proteins in each experimental model was evaluated by protein array analysis. To gain further evidence of the effect of TAMs on oxidative stress, malondialdehyde was measured through high-performance liquid chromatography, and the total nonenzymatic antioxidant levels and the production of nitrites were measured through colorimetric assays. The results demonstrated that TAMs exerted a dual role in the response of C26 cells to 5-FU administration in the co-culture model. Thus, on one side, TAMs sensitized C26 cells to 5-FU administration through inhibition of the production of inflammatory and angiogenic proteins in these cancer cells; however, they also protected cancer cells against 5-FU-induced oxidative stress. Collectively, the present findings suggest that the combined administration of 5-FU with pharmacological agents that prevent TAMs to maintain the physiological range of tumor cell oxidative stress may highly improve the therapeutic potential of this drug.

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Section: Effects On the Production Of Inflammatory/angiogenic Proteinsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Dual role of macrophages in the response of C26 colon carcinoma cells to 5-fluorouracil administration

et al. 2016

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“…24,25) The tumor volume reached 100-150 mm 3 at day 6 after the inoculation of MDA-MB-453 cells, and then TTZ-LAK and CD3-LAK cells were intravenously administered twice each week for 14 d from day 6. The solid tumors were weighed after anatomizing the mice after 21 d of inoculation of MDA-MB-453 cells.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effects of Autologous Lymphocytes Activated with Trastuzumab for Xenograft Mouse Models of Human Breast Cancer

Nakagawa

Matsuoka

Ichihara

et al. 2013

Biological & Pharmaceutical Bulletin

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Trastuzumab (TTZ) is molecular targeted drug used for metastatic breast cancer patients overexpressing human epidermal growth factor receptor 2 (HER2). Therapeutic effects of lymphocytes activated with TTZ (TTZ-LAK). p185 HER2 has partial homology with the epidermal growth factor receptor and shares intrinsic tyrosine kinase activity with that receptor. HER2 overexpressed in human breast cancers correlated with poor clinical outcome in women with breast cancers.1-3) HER2 is known as epidermal growth factor receptor (ErbB) 2 of the tyrosine kinase (TK) receptor, belonging to ErbB growth factor receptor family. There are four members of HER family receptors; epidermal growth factor receptor (EGFR)/ErbB1/ HER1, HER2/ErbB2, HER3/ErbB3, and HER/ErbB4.3) HER family receptors are activated by ligand-induced dimerization, or receptor pairing. Dimerization is a critical step in HER family-mediated signaling, and HER receptors are able to homodimerize or heterodimerize with other HER family members. HER2 is the preferred dimerization partner for all HER family receptors. However, there are no known endogenous ligands that bind to HER2. 4)The extracellular domain of HER2 is in a conformation that is open and ready for dimerization. So, molecules such as monoclonal antibodies would bind to the extracellular domain of HER2 to suppress those activity. Several monoclonal antibodies (mAbs) directed against HER2 ectodomain that specifically inhibit the growth of tumor cell lines overexpressing HER2 have been developed. 5) Trastuzumab (TTZ) is a humanized immunoglobulin G1 kappa (IgG1κ) light chain mAb in which the complementary-determining regions (CDR) of a HER2-specific mouse mAb were joined to in human immunoglobulin variable regions.5) TTZ binds to the domain IV of the extracellular segment of the HER2/neu receptor. Because TTZ belong to IgG1, its effects may be related to Fab (antigen binding fragment) or Fc (crystallizable fragment) regions.6) It has been reported that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the antitumor activity of TTZ. 7) Although the mechanisms underlying the action of TTZ are still not fully understood, inhibitory effects of TTZ by cell cycle arrest in G1 and induction of apoptosis on the growth of HER2-positive breast cancer cells in vitro have been reported.8) The combination chemotherapy with TTZ has been shown to improve survival for women with HER2-overexpressing metastatic breast cancer patients. [9][10][11] However, there were severe side-effects in combination chemotherapy. 1,6,12,13) On the other hand, immunotherapy using lymphocyte stimulated with immunomodulators such as cytokines was noted in cancer therapy as attractive approach, since there is no serious side effects in immunotherapy. Significant prolongation in survival and disease free period in group of immunotherapy compared with no-treatment group have been reported. 14)Yoshida et al. have studied metastasis mechanism of cancer cells 15,16) and for clinical applications of immunotherapy using CD3-a...

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“…LPs-PLP reduced TAM-mediated production of proangiogenic factors such as granulocytemacrophage colony-stimulating factor, macrophage colonystimulating factor, IL-1α, IL-1β, IL-6, and IL-9, but the production of antiangiogenic factors is hardly affected. 83 The therapeutic efficacy of DOXIL ® was evaluated in B16-F10 melanoma-bearing mice in the presence or absence of TAMs, 84 which was controlled using PEG-liposomes loaded with clodronate injected 24 hours before the actual treatment. PEG-liposomes loaded with clodronate suppressed tumor progression through the reduction of the proangiogenic function of TAMs.…”

Section: Molecular Targeting Of Molecular Nanoparticlesmentioning

confidence: 99%

Molecular targeting of liposomal nanoparticles to tumor microenvironment

Zhao¹,

Rodriguez²

2012

IJN

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Liposomes are biodegradable and can be used to deliver drugs at a much higher concentration in tumor tissues than in normal tissues. Both passive and active drug delivery by liposomal nanoparticles can significantly reduce the toxic side effects of anticancer drugs and enhance the therapeutic efficacy of the drugs delivered. Active liposomal targeting to tumors is achieved by recognizing specific tumor receptors through tumor-specific ligands or antibodies coupled onto the surface of the liposomes, or by stimulus-sensitive drug carriers such as acid-triggered release or enzyme-triggered drug release. Tumors are often composed of tumor cells and nontumor cells, which include endothelial cells, pericytes, fibroblasts, stromal, mesenchymal cells, innate, and adaptive immune cells. These nontumor cells thus form the tumor microenvironment, which could be targeted and modified so that it is unfavorable for tumor cells to grow. In this review, we briefly summarized articles that had taken advantage of liposomal nanoparticles as a carrier to deliver anticancer drugs to the tumor microenvironment, and how they overcame obstacles such as nonspecific uptake, interaction with components in blood, and toxicity. Special attention is devoted to the liposomal targeting of anticancer drugs to the endothelium of tumor neovasculature, tumor associated macrophages, fibroblasts, and pericytes within the tumor microenvironment.

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Antitumor Activity of Liposomal Prednisolone Phosphate Depends on the Presence of Functional Tumor-Associated Macrophages in Tumor Tissue

Cited by 88 publications

References 42 publications

Dual role of macrophages in the response of C26 colon carcinoma cells to 5-fluorouracil administration

Dual role of macrophages in the response of C26 colon carcinoma cells to 5-fluorouracil administration

Therapeutic Effects of Autologous Lymphocytes Activated with Trastuzumab for Xenograft Mouse Models of Human Breast Cancer

Molecular targeting of liposomal nanoparticles to tumor microenvironment

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