Delayed lethal response to<i>Aspergillus fumigatus</i>infection in sarcoma 180 tumor-bearing mice

Okawa, Yoshio; Murata, Yoshiko; Suzuki, Masuko; Itō, Makoto; Hotchi, Masao; Suzuki, Shigeo

doi:10.1111/j.1574-695x.2002.tb00611.x

Cited by 3 publications

(2 citation statements)

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“…[2][3][4][5][6] The protective activity of allogeneic sarcoma 180 tumor-bearing mice against Candida albicans and Aspergillus fumigatus infections has been reported in our previous papers. [7][8][9][10][11] It has also been reported that there is a significant delay in the lethal response to C. albicans in mice bearing Lewis lung carcinoma. 12) However, the mechanisms of such an effect have yet to be fully elucidated.…”

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Role of Polymorphonuclear Leukocytes in the Resistance of Tumor-Bearing Mice against Candida albicans Infection

Okawa

Kobayashi

Sakai

et al. 2004

Biological & Pharmaceutical Bulletin

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Opportunistic fungal infection occurring frequently in a compromised host is one of the most important problems in modern medicine, because of the difficulty of treatment and the frequency with which such infections progress to a lifethreatening condition. There are many papers reports on the increased susceptibility of tumor-bearing hosts to systemic fungal infections. [2][3][4][5][6] The protective activity of allogeneic sarcoma 180 tumor-bearing mice against Candida albicans and Aspergillus fumigatus infections has been reported in our previous papers. [7][8][9][10][11] It has also been reported that there is a significant delay in the lethal response to C. albicans in mice bearing Lewis lung carcinoma. 12) However, the mechanisms of such an effect have yet to be fully elucidated. We reported that the number of peripheral blood polymorphonuclear leukocytes (PMNs) dramatically increased in sarcoma 180 tumor-bearing mice. [7][8][9] We also investigated the producibility of the granulocyte-macrophage colony-stimulating factor from the tumor cells. 9,10) We thought that this phenomenon should be investigated not only in allogeneic tumor-bearing mice but also in syngeneic tumor-bearing mice. In the present study, to demonstrate further the importance of PMNs in the resistance of tumor-bearing mice against C. albicans, we conducted a protection assay against the infection using allogeneic (sarcoma 180) and syngeneic (Meth A fibrosarcoma [Meth A] and MM 46 mammary carcinoma [MM46]) solid tumor-bearing mice over the course of 3 weeks after tumor cell transplantation. Furthermore, we investigated in detail the involvement of PMNs from tumor-bearing mice as the likely mechanism of such protection. MATERIALS AND METHODS Mice and TumorsMale 6-to 8-week-old ddY, BALB/c, and C3H/He mice were obtained from the Shizuoka Laboratory Animal Center, Hamamatsu, Japan. Sarcoma 180 (1ϫ10 6 ), 3-methylcholanthrene-induced Meth A fibrosarcoma (Meth A, 1ϫ10 6 ), and MM 46 mammary carcinoma (MM46, 3ϫ10 6 ) were transplanted subcutaneously in the ddY, BALB/c, and C3H/He mice, respectively. Cyclophosphamide (CY)-treated mice were prepared as follows: 16 d after tumor transplantation, the mice were injected intraperitoneally with a single dose of 15, 50, or 200 mg/kg of CY (Cytoxan, Shionogi Co., Ltd., Osaka, Japan).Fungus The C. albicans NIH A-207 strain was kindly donated by Dr. T. Shinoda, Department of Microbiology, Meiji College of Pharmacy, Tokyo, Japan, and was maintained on Sabouraud agar slants. For this study, the fungus was cultured in a Sabouraud liquid medium which was shaken at 27°C for 48 h.Infection-Protection Assay One, 2, and 3 weeks after tumor cell transplantation, the mice were inoculated intravenously with 2ϫ10 6 viable C. albicans cells. The mice bearing only the solid tumor began dying by week 4; therefore reliable data could not be obtained beyond 3 weeks. In the CY experiment, 4 d after CY administration, the mice were infected intravenously with the fungal cells. The mortality rate of the mice was recorded for...

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Role of Polymorphonuclear Leukocytes in the Resistance of Tumor-Bearing Mice against Candida albicans Infection

Okawa

Kobayashi

Sakai

et al. 2004

Biological & Pharmaceutical Bulletin

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“…Alternative procedures were developed to allow invasive aspergillosis in very original opportunistic contexts, like septic infections following caecal ligation and puncture (Benjamim et al, 2003, 2005), as well as cancerous disease using 1.0 × 10 6 S-180 tumor cells suspension (Okawa et al, 2002), and rhinosinusitis after unilateral nasal obstruction with sponges (Zhang et al, 2013). In addition to all these abovementioned methods, rodents were sometimes fed with low-diet hypo-protein regimen to mimic the malnourished status of the weakest human patients that are usually infected with A. fumigatus in hospitals (Miyazaki et al, 1993; Mitsutake et al, 1995; Chandenier et al, 2009; Lo Giudice et al, 2010; Desoubeaux and Chandenier, 2012; Desoubeaux et al, 2014b).…”

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Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Désoubeaux

Cray

2017

Front. Microbiol.

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Invasive aspergillosis has been studied in laboratory by the means of plethora of distinct animal models. They were developed to address pathophysiology, therapy, diagnosis, or miscellaneous other concerns associated. However, there are great discrepancies regarding all the experimental variables of animal models, and a thorough focus on them is needed. This systematic review completed a comprehensive bibliographic analysis specifically-based on the technical features of rodent models infected with Aspergillus fumigatus. Out the 800 articles reviewed, it was shown that mice remained the preferred model (85.8% of the referenced reports), above rats (10.8%), and guinea pigs (3.8%). Three quarters of the models involved immunocompromised status, mainly by steroids (44.4%) and/or alkylating drugs (42.9%), but only 27.7% were reported to receive antibiotic prophylaxis to prevent from bacterial infection. Injection of spores (30.0%) and inhalation/deposition into respiratory airways (66.9%) were the most used routes for experimental inoculation. Overall, more than 230 distinct A. fumigatus strains were used in models. Of all the published studies, 18.4% did not mention usage of any diagnostic tool, like histopathology or mycological culture, to control correct implementation of the disease and to measure outcome. In light of these findings, a consensus discussion should be engaged to establish a minimum standardization, although this may not be consistently suitable for addressing all the specific aspects of invasive aspergillosis.

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Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis

Altés

Remacha

Sarda

et al. 2004

Bone Marrow Transplant

120

106

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Summary:Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n ¼ 24) or allogeneic (n ¼ 35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 lmol/g dry weight (7.7 mg/g; range 31-631 lmol/g). In total, 4/32 (12%) patients with HIC o150 lmol/g and 10/27 (37%) with hepatic iron X150 lmol/g showed invasive aspergillosis at autopsy (P ¼ 0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P ¼ 0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.

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Delayed lethal response toAspergillus fumigatusinfection in sarcoma 180 tumor-bearing mice

Cited by 3 publications

References 21 publications

Role of Polymorphonuclear Leukocytes in the Resistance of Tumor-Bearing Mice against Candida albicans Infection

Role of Polymorphonuclear Leukocytes in the Resistance of Tumor-Bearing Mice against Candida albicans Infection

Rodent Models of Invasive Aspergillosis due to Aspergillus fumigatus: Still a Long Path toward Standardization

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis

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