scholarly journals Canine Natural Killer Cell-Derived Exosomes Exhibit Antitumor Activity in a Mouse Model of Canine Mammary Tumor

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jienny Lee ◽  
Se-A Lee ◽  
Na-Yeon Gu ◽  
So Yeon Jeong ◽  
Jeong Su Byeon ◽  
...  
Keyword(s):  
Mouse Model ◽  
B Cell ◽  
Mammary Tumor ◽  
Mammary Carcinoma ◽  
Tumor Size ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Tumor Group ◽  
Tnf Α

Natural killer (NK) cells are key immune cells engaged in fighting infection and malignant transformation. In this study, we found that canine NK cell-derived exosomes (NK-exosomes) separated from activated cytotoxic NK cell supernatants express specific markers including CD63, CD81, Alix, HSP70, TSG101, Perforin 1, and Granzyme B. We examined the antitumor effects of NK-exosomes in an experimental murine mammary tumor model using REM134 canine mammary carcinoma cell line. We observed changes in tumor size, tumor initiation, progression, and recurrence-related markers in the control, tumor group, and NK-exosome-treated tumor group. We found that the tumor size in the NK-exosome-treated tumor group decreased compared with that of the tumor group in the REM134-driven tumorigenic mouse model. We observed significant changes including the expression of tumorigenesis-related markers, such as B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1), vascular endothelial growth factor (VEGF), matrix metallopeptidase-3 (MMP-3), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), multidrug resistance protein (MDR), tumor suppressor protein p53 (p53), proliferating cell nuclear antigen (PCNA), and the apoptotic markers, B cell lymphoma-2 associated X (Bax) and B cell lymphoma-extra large (Bcl-xL) belonging to the Bcl-2 family, in the tumor group compared with those in the control group. The expression of CD133, a potent cancer stem cell marker, was significantly higher than that of the control. By contrast, the NK-exosome-treated tumor group exhibited a significant reduction in Bmi-1, MMP-3, IL-1β, IL-6, TNF-α, Bax, Bcl-xL, and PCNA expression compared with that in the tumor group. Furthermore, the expression of CD133, which mediates tumorigenesis, was significantly decreased in the NK-exosome-treated tumor group compared with that in the tumor group. These findings indicate that canine NK-exosomes represent a promising therapeutic tool against canine solid tumors, including mammary carcinoma.

TNF-α Receptor 1 Expression Predicts Poor Prognosis of Diffuse Large B-cell Lymphoma, Not Otherwise Specified

2014 ◽  
Vol 38 (8) ◽  
pp. 1138-1146 ◽  
Author(s):  
Shoko Nakayama ◽  
Taiji Yokote ◽  
Motomu Tsuji ◽  
Toshikazu Akioka ◽  
Takuji Miyoshi ◽  
...  
Keyword(s):  
B Cell ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Not Otherwise Specified ◽  
Large B Cell Lymphoma ◽  
Tnf Α ◽  
Large B Cell

A combination of 5-fluorouracil and membrane-bound antibody inhibits B-cell lymphoma growth in a mouse model system

2007 ◽  
Vol 48 (2) ◽  
pp. 406-409 ◽  
Author(s):  
Mattia Bonsignori ◽  
Sybil D'Costa ◽  
Sherri Surman ◽  
Julia L. Hurwitz
Keyword(s):  
Mouse Model ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Model System ◽  
Membrane Bound ◽  
Mouse Model System

scholarly journals Preventive Effect of Lactobacillus fermentum CQPC08 on 4-Nitroquineline-1-Oxide Induced Tongue Cancer in C57BL/6 Mice

Foods ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 93 ◽  
Author(s):  
Bihui Liu ◽  
Jing Zhang ◽  
Ruokun Yi ◽  
Xianrong Zhou ◽  
Xingyao Long ◽  
...  
Keyword(s):  
Mouse Model ◽  
B Cell ◽  
Mrna Expression ◽  
Cell Lymphoma ◽  
Tongue Cancer ◽  
B Cell Lymphoma ◽  
Lactobacillus Fermentum ◽  
Phagocytic Index ◽  
Mouse Serum ◽  
Preventive Effect

Lactobacillus fermentum CQPC08 (LF-CQPC08) is a newly discovered strain of bacteria isolated and identified from traditional pickled vegetables in Sichuan, China. We used 4-nitroquinoline 1-oxide to establish an experimental tongue cancer mouse model to evaluate the preventive effect of LF-CQPC08 on tongue cancer in vivo. Lactobacillus delbruechii subsp. bulgaricus, is a common commercial strain and is used as a positive control to compare the effect with LF-CQPC08. The preventive strength and mechanism of LF-CQPC08 on tongue cancer were determined by measuring the biochemical indicators in mouse serum and tissues. Our results showed LF-CQPC08 inhibits the decline of splenic index, thymus index, percentage of phagocytic macrophages, and phagocytic index effectively. LF-CQPC08 also increased levels of mouse serum granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), immunoglobulin (Ig)G, IgM levels of serum interleukin (IL)-4, IL-12, tumor necrosis factor-alpha, and interferon-gamma levels, thereby inhibiting the decline in immunity caused by tongue cancer. It also increased the activity levels of superoxide dismutase and glutathione peroxidase and decreased the levels of malondialdehyde in the tissues of the tongue cancer mouse model, thereby suppressing the oxidative stress damage in the tissue caused by tongue cancer. Through quantitative PCR, LF-CQPC08 upregulated the mRNA expression of nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione-S-transferases-π (GST-π), and Bcl-2-associated X protein (Bax), and downregulated the mRNA expression of p53, p63, p73, phosphatase and tensin homolog (PTEN), B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL) in the tongue tissues of the tongue cancer mouse. These results indicated that LF-CQPC08 reduced the influence of tongue cancer on the immune system and oxidative balance and improved the immunity and enhanced antioxidant capacity of the mouse model, thereby preventing tongue cancer. LF-CQPC08 could be used as a microbial resource with a preventive effect on tongue cancer.

scholarly journals A multi-institutional and case-matched control study on treatment outcomes of consolidative radiotherapy after a full course of R-CHOP compared with R-CHOP alone in Stage I–II diffuse large B-cell lymphoma (KROG 17-02)

2019 ◽  
Vol 60 (5) ◽  
pp. 677-684
Author(s):  
Mi Joo Chung ◽  
Won Kyung Cho ◽  
Dongryul Oh ◽  
Keun-Yong Eom ◽  
Jin Hee Kim ◽  
...  
Keyword(s):  
B Cell ◽  
Treatment Outcomes ◽  
Tumor Size ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Chop Chemotherapy ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract We compared treatment outcomes between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy alone with R-CHOP followed by consolidative radiation therapy (RT) in diffuse large B-cell lymphoma (DLBCL). We analyzed 404 patients with Stage I–II DLBCL who received six to eight cycles of R-CHOP and achieved a good response after a full course of chemotherapy. Propensity-score matching was used to assess the role of consolidative RT. The R-CHOP alone group (n = 184) was matched in a 1:2 ratio with the R-CHOP plus RT group (n = 92). Twenty-four (13.0%) of 184 patients receiving R-CHOP alone and 8 (8.7%) of 92 patients receiving R-CHOP plus RT had bulky diseases (>7.5 cm). A Deauville score of 1–2 was achieved for 159 (86.4%) of 184 patients receiving R-CHOP alone and 84 (91.3%) of 92 patients receiving R-CHOP plus RT. After a median follow-up time of 42 months, the recurrence-free survival (RFS) rate (86.7% vs 93.0%, P = 0.464) and overall survival rate (88.3% vs 95.1%, P = 0.295) at 5 years did not differ significantly between the R-CHOP alone and R-CHOP plus RT arms. In the additional multivariate analyses, large tumor size (>7.5 cm) was significantly associated with decreased RFS (hazard ratio, 2.368 and confidence interval, 1.837–6.697; P = 0.048). Consolidative radiation was not a significant factor for RFS (P = 0.563). Tumor size was a significant factor for RFS in the rituximab era. The outcome of omitting consolidative RT for good responders after six to eight cycles of R-CHOP chemotherapy was acceptable in early-stage DLBCL without a bulky disease.

Chloroquine Inhibits Autophagy, Enhances p53-Dependent Apoptosis, and Delays Tumor Recurrence in a Mouse Model of B Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2421-2421 ◽  
Author(s):  
Ravi K. Amaravadi ◽  
Duonan Yu ◽  
Andrei Thomas-Tikhonenko ◽  
Craig B. Thompson
Keyword(s):  
Mouse Model ◽  
Fusion Protein ◽  
B Cell ◽  
Nuclear Localization ◽  
Target Genes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Recurrent Tumors

Abstract Burkitt’s lymphoma is an example of an aggressive B cell neoplasm characterized by overexpression of the c-myc oncogene and frequent inactivation of the tumor suppressor gene p53. A non-transgenic mouse model of Burkitt’s lymphoma was generated by retroviral transduction of the human c-myc gene into bone marrow cells derived from the p53-estrogen receptor (p53ER) knock-in mouse. The resulting myc/p53ER cells produce an aggressive B cell lymphoma when injected subcutaneously into the flanks of syngeneic mice. When tumor-bearing mice are treated with tamoxifen intraperitoneally, the p53ER fusion protein is targeted to the nucleus where p53-dependent apoptosis can take place. On successive in vivo passages, cells develop the ability to survive p53 activation and escape p53ER-dependent apoptosis despite tamoxifen treatment and nuclear localization of the p53ER fusion protein. We hypothesized that cells resistant to p53-dependent apoptosis utilize autophagy as an essential survival mechanism. Thus, these tumors could be sensitive to chloroquine, a lysosomotropic inhibitor of autophagy that has been used extensively in humans as an antimalarial and for the treatment of rheumatoid arthritis. Daily intraperitoneal chloroquine or hydroxychloroquine treatment of mice bearing myc/p53ER tumors in the absence of tamoxifen resulted in a delay in tumor growth. When tamoxifen was added to induce nuclear localization of p53ER, mice that received tamoxifen plus chloroquine had a complete tumor response while mice that received tamoxifen plus saline had transient tumor shrinkage followed quickly by regrowth. Tamoxifen plus chloroquine treatment enhanced the expression of p53-dependent target genes and increased caspase activation compared to tamoxifen plus saline treatment. A higher percentage of cells in tumors treated with tamoxifen plus chloroquine underwent apoptosis compared to tumors treated with tamoxifen plus saline. Moreover, tumors that recurred in the mice treated with daily tamoxifen plus chloroquine did so after a significantly longer latency period then mice treated with tamoxifen plus saline. Recurrent tumors showed loss of expression of p53 target genes. Electron microscopy of recurrent tumors confirmed the accumulation of vacuoles in chloroquine treated tumors compared to controls, suggesting inhibition of lysosome function leads to the accumulation of ineffective autophagic vacuoles. These results indicate that inhibiting autophagy with lysosomotropic chloroquine derivatives could be a useful therapeutic addition to treatment regimens for aggressive B cell lymphomas.

Clinical Outcome of 119 Children with Non-Hodgkin Lymphoma Treated in a Single Center in China

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5299-5299
Author(s):  
Yonghong Zhang ◽  
Ling Jin ◽  
Jing Yang ◽  
Yanlong Duan ◽  
Chunjv Zhou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoblastic Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Pathologic Classification

Abstract One hundred and nineteen children with non-Hodgkin lymphoma were treated between February 2003 and December 2006 in Beijing Children’s Hospital on BCH-2003-NHL protocol. The diagnosis was made by histopathology of the biopsied tissue and/or bone marrow, and disease was classified according to WHO-2001 pathologic classification. We applied modified LMB89 protocol to cases with B-cell lymphoma; modified BFM90-ALL protocol for lymphoblastic lymphoma and cutaneous T-cell/NK cell lymphoma; and modified BFM90-ALCL protocol for anaplastic large-cell lymphoma (ALCL). There were 50 cases (42%) of B cell lymphoma including 32 cases of Burkitt¡’s lymphoma, 10 cases of Burkitt-like lymphoma and 8 cases of diffuse large B cell lymphoma; 44 cases (37%) of lymphoblastic lymphoma; 19 cases (16%) of ALCL; and 6 cases (5%) of cutaneous T-cell/NK cell lymphoma. The 85 boys and 34 girls (ratio, 2.5:1) ranged in age from 2 to 15 years (median, 7.8 years) at diagnosis. B cell lymphoma typically presented as abdomen mass and acute abdomen; nasopharynx and tonsil were also common sites of involvement. Lymphoblastic lymphoma generally presented with mediastinal mass and bone marrow involvement. There was no typical presentation for ALCL. According to the St. Jude staging system, 19 cases had stage I–II, and 94 cases stage III–VI diseases (exclude 6 cases of cutaneous T-cell/NK cell lymphoma). Seven cases had CNS involvement and 25 cases involved bone marrow. The treatment duration was 2 to 8 months for B-cell lymphoma, 2.5 to 3 years for lymphoblastic lymphoma and 1 to 1.5 years for ALCL. The follow-up rate was 100% and median observation period was 23 months. The overall survival (OS) at 3 years was 90.7% and the 3-year event-free survival (EFS) estimate was 82.3%. For B-cell lymphoma, 3-year OS was 88.68% and 3-year EFS was 81.8%. For lymphoblastoma lymphoma, the rates were 89.3% and 69.4%, respectively. All cases of ALCL are alive with on undergoing treatment for relapse. Patients with ALCL achieved the best 3-year OS (100%) and had 3-year EFS of 94.2%. Grade 3 or 4 bone marrow suppression occurred in 97.5% of patients with B-cell lymphoma, 100% of those with lymphoblastic lymphoma and 89.5% of cases with ALCL. As of to date, 11 patients have died, the causes of death include infection (n=4), abandonment of therapy (n=6) and relapse (n=1). Univarate analysis showed that stage IV disease, failure to achieve complete remission after 3 months of treatment, and bulky mass are were associated with poor prognosis £all P values <0.05£©. In summary, we have achieved excellent treatment results using modified international protocols. Infection and financial problem remained the main reasons of treatment failure.

A Germinal Center- Derived B Cell Lymphoma Model

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2008-2008
Author(s):  
Ryan T Phan ◽  
Khang Nguyen ◽  
Sonia Romero ◽  
Alice Nicolson ◽  
Phillipp Nham ◽  
...  
Keyword(s):  
B Cells ◽  
Mouse Model ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chromosomal Translocations ◽  
Dna Breaks ◽  
Dna Rearrangements ◽  
Human B Cell

Abstract Abstract 2008 Most human B-cell lymphomas represent mature phenotypes of germinal center (GC) or post-GC origin and are frequently associated with chromosomal translocations, often involving the rearrangement of immunoglobulin (Ig) loci to various cellular oncogenes, leading to oncogenic activation. The mechanisms underlying these processes, however, are not well understood. Several studies suggest that these genetic lesions arise from errors of physiologic DNA rearrangements in GC B cells, namely class switch recombination (CSR) and somatic hypermutation (SHM). Here we report the generation of a mouse model in which DNA breaks are physiologically instituted in mature B cells, yet inefficiently repaired via specific deletion of DNA repair gene XRCC4 in GC B cells, thus effectively creating an in vivo environment for errors in DNA rearrangements. These activated B cells exhibit significant increased chromosomal IgH locus breaks and reduced CSR. In p53-deficient background, these mice develop B-cell lymphoma from 5.5 to 16 months. These clonally developed tumors characteristically harbor chromosomal translocations and phenotypically resemble mature phenotypes. Many of these tumors bear mutated V genes, suggesting that those cells have transited through GC. Thus, this mouse model mimics human B-cell lymphoma and might be useful for the development of therapeutic interventions in B-cell lymphoma. Disclosures: No relevant conflicts of interest to declare.

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