scholarly journals Candida Albicans Activated Splenocytes Promote Strong Immune Responses in a Murine Model of Breast Cancer

2021 ◽  
Author(s):  
Siavash Mashhouri ◽  
Erfan Yarahmadi ◽  
Seyyed Meysam Abtahi Froushani
Keyword(s):  
Breast Cancer ◽  
Candida Albicans ◽  
Immune Responses ◽  
Survival Curve ◽  
Tumor Development ◽  
Yeast Form ◽  
Tumor Bearing ◽  
4T1 Cells ◽  
Breast Cancer Growth

Background: The potential of Candida albicans to modulate antigen-presenting cells maturation has been documented in past studies. Dendritic cells are critical modulators in the orchestration of adaptive immune responses alongside myeloid subtypes, which play an important role in the presentation of antigens to T cells. The aim of this study was to evaluate the efficacy of splenocytes activated with the extract of heated 4T1 cells and the yeast form of C. albicans against breast cancer growth in vivo. Methods: 4T1 cells were subcutaneously injected into the left flanks of female BALB/c mice (n=40). At a time when palpable tumors had developed, experimental groups were immunized twice at one-week interim with either activated splenocytes with the extract of heated 4T1 or the killed preparation of yeast form of C. albicans or a combination of the two-One week after the second injection, one-half of animals (n=20) were euthanized to investigate the immune response profile. Results: Administration of activated splenocytes with the combination protocol caused a favorable survival curve and slower rates of tumor development compared to other tumor-bearing mice. Moreover, combination therapy significantly increased the secretion of IFN-γ, respiratory burst and nitric oxide production and conversely diminished the secretion of IL-4, IL-10 and TGF-β in the splenocyte population. Conclusion: Since the murine 4T1 cell line is similar to the final stage of human breast carcinoma, we postulate that activated splenocytes with the extract of heated 4T1 cells and yeast form of C. albicans can reduce tumor development in tumor-bearing mice.

scholarly journals Eupatorin Suppressed Tumor Progression and Enhanced Immunity in a 4T1 Murine Breast Cancer Model

2020 ◽  
Vol 19 ◽  
pp. 153473542093562
Author(s):  
Nursyamirah Abd Razak ◽  
Swee Keong Yeap ◽  
Noorjahan Banu Alitheen ◽  
Wan Yong Ho ◽  
Chean Yeah Yong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Development ◽  
Interferon Γ ◽  
Mice Model ◽  
Cytotoxic Effects ◽  
Breast Cancer Model ◽  
Tnf Α ◽  
4T1 Cells ◽  
Cancer Agent

Eupatorin is a polymethoxy flavone extracted from Orthosiphon stamineus and was reported to exhibit cytotoxic effects on several cancer cell lines. However, its effect as an anti–breast cancer agent in vivo has yet to be determined. This study aims to elucidate the potential of eupatorin as an anti–breast cancer agent in vivo using 4T1 challenged BALB/c mice model. In this article, BALB/c mice (20-22 g) challenged with 4T1 cells were treated with 5 mg/kg or 20 mg/kg eupatorin, while the untreated and healthy mice were fed with olive oil (vehicle) via oral gavage. After 28 days of experiment, the mice were sacrificed and blood was collected for serum cytokine assay, while tumors were harvested to extract RNA and protein for gene expression assay and hematoxylin-eosin staining. Organs such as spleen and lung were harvested for immune suppression and clonogenic assay, respectively. Eupatorin (20 mg/kg) was effective in delaying the tumor development and reducing metastasis to the lung compared with the untreated mice. Eupatorin (20 mg/kg) also enhanced the immunity as the population of NK1.1+ and CD8+ in the splenocytes and the serum interferon-γ were increased. Concurrently, eupatorin treatment also has downregulated the expression of pro-inflammatory and metastatic related genes (IL-1β. MMP9, TNF-α, and NF-κB). Thus, this study demonstrated that eupatorin at the highest dosage of 20 mg/kg body weight was effective in delaying the 4T1-induced breast tumor growth in the animal model.

scholarly journals Combination of Propranolol and Heated 4T1 Cells Elicits Beneficial Response Against Mouse Model of Breast Cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Payman Tavakoli ◽  
Seyyed Meysam Abtahi Froushani ◽  
Asghar Aliyari
Keyword(s):  
Breast Cancer ◽  
Tumor Antigens ◽  
Synergistic Effects ◽  
Survival Curve ◽  
Negative Control ◽  
Tumor Bearing ◽  
Beneficial Response ◽  
4T1 Cells ◽  
Cellular Immune ◽  
Combined Immunotherapy

Background: Induction of Th1 responses against tumor antigens may be a useful strategy to control malignancy. In this respect, previous studies have shown that beta-adrenoreceptor antagonists can promote cellular immune responses. Objectives: This survey was done to evaluate the beneficiary of a new immunotherapy method against breast cancer made by mixing heated 4T1 cells and propranolol, as an adjuvant. Methods: Subcutaneously injected live 4T1 cells (1 × 104) were used to induce breast cancer in six to eight-week-old female Balb/c mice. when all mice had a palpable tumor, immunotherapy was dawned. Mice in the treatment groups were vaccinated, twice at a one-week interval, with the extract of heated 4T1(1 × 105) either alone or in combination with propranolol (6 mg/kg). Negative control mice received phosphate-buffered saline (PBS) as the same schedule. One-half of the mice were euthanized one week after the last vaccination to investigate the immune response profile. Other animals were kept until death occurred spontaneously. Results: Combined immunotherapy with propranolol and extract of heated 4T1 had synergistic effects, causing a more desirable survival curve and slower tumor growth when compared to other tumor-bearing mice receiving only heated 4T1 or PBS. Furthermore, combined immunotherapy significantly augmented the production of IFN-γ nitric oxide production, respiratory burst, and cytotoxicity of natural killer cells in the splenocyte culture of tumor-bearing mice. Conversely, combined immunotherapy significantly regressed the production of TGF-β and IL-10 in the splenocyte population compared to cytokine production by splenocytes from other groups. Conclusions: Combined heated 4T1 cells with propranolol promote beneficial outcomes in the animal model of breast cancer.

scholarly journals Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy

2021 ◽  
Vol 22 (11) ◽  
pp. 5930
Author(s):  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Tianjiao Luo ◽  
Ralf Hass
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Development ◽  
Cellular Interactions ◽  
Hybrid Cells ◽  
Induced Tumors ◽  
Culture Model ◽  
Gene Expression Levels

Direct cellular interactions of MDA-MB-231cherry breast cancer cells with GFP-transduced human mesenchymal stroma/stem-like cells (MSCGFP) in a co-culture model resulted in spontaneous cell fusion by the generation of MDA-MSC-hyb5cherry GFP breast cancer hybrid cells. The proliferative capacity of MDA-MSC-hyb5 cells was enhanced about 1.8-fold when compared to the parental MDA-MB-231cherry breast cancer cells. In contrast to a spontaneous MDA-MB-231cherry induced tumor development in vivo within 18.8 days, the MDA-MSC-hyb5 cells initially remained quiescent in a dormancy-like state. At distinct time points after injection, NODscid mice started to develop MDA-MSC-hyb5 cell-induced tumors up to about a half year later. Following tumor initiation, however, tumor growth and formation of metastases in various different organs occurred rapidly within about 10.5 days. Changes in gene expression levels were evaluated by RNA-microarray analysis and revealed certain increase in dormancy-associated transcripts in MDA-MSC-hyb5. Chemotherapeutic responsiveness of MDA-MSC-hyb5 cells was partially enhanced when compared to MDA-MB-231 cells. However, some resistance, e.g., for taxol was detectable in cancer hybrid cells. Moreover, drug response partially changed during the tumor development of MDA-MSC-hyb5 cells; this suggests the presence of unstable in vivo phenotypes of MDA-hyb5 cells with increased tumor heterogeneity.

scholarly journals Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for treatment of breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dobrin Draganov ◽  
Zhen Han ◽  
Aamir Rana ◽  
Nitasha Bennett ◽  
Darrell J. Irvine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Synergistic Activity ◽  
Primary Tumors ◽  
T Cell Infiltration ◽  
Cancer Cell Death ◽  
Bona Fide

AbstractWe show that treatment with the FDA-approved anti-parasitic drug ivermectin induces immunogenic cancer cell death (ICD) and robust T cell infiltration into breast tumors. As an allosteric modulator of the ATP/P2X4/P2X7 axis which operates in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations including myeloid cells and Tregs, resulting in enhanced Teff/Tregs ratio. While neither agent alone showed efficacy in vivo, combination therapy with ivermectin and checkpoint inhibitor anti-PD1 antibody achieved synergy in limiting tumor growth (p = 0.03) and promoted complete responses (p < 0.01), also leading to immunity against contralateral re-challenge with demonstrated anti-tumor immune responses. Going beyond primary tumors, this combination achieved significant reduction in relapse after neoadjuvant (p = 0.03) and adjuvant treatment (p < 0.001), and potential cures in metastatic disease (p < 0.001). Statistical modeling confirmed bona fide synergistic activity in both the adjuvant (p = 0.007) and metastatic settings (p < 0.001). Ivermectin has dual immunomodulatory and ICD-inducing effects in breast cancer, converting cold tumors hot, thus represents a rational mechanistic partner with checkpoint blockade.

scholarly journals Yanghe Huayan decoction inhibits the capability of trans-endothelium and angiogenesis of HER2+ breast cancer via pAkt signaling

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Xiao-Fei Liu ◽  
Jing-Wei Li ◽  
Hong-Zhi Chen ◽  
Zi-Yuan Sun ◽  
Guang-Xi Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chinese Medicine ◽  
Precancerous Lesion ◽  
Tumor Development ◽  
Akt Activation ◽  
Her2 Breast Cancer ◽  
Prevention And Treatment

Abstract Background: Yanghe Huayan Decoction (YHD), a traditional Chinese medicine, is one of the most common complementary medicine currently used in the treatment of breast cancer (BC). It has been recently linked to suppress precancerous lesion and tumor development. The current study sought to explore the role of YHD on trans-endothelium and angiogenesis of BC. Methods: HER2+ BC cells were treated with YHD, Trastuzumab, or the combination in vitro and in vivo to compare the effects of them on trans-endothelium and angiogenesis features. The present study also investigated the potential molecular mechanism of YHD in inhibiting angiogenesis of BC. Results: YHD significantly suppressed the invasion and angiogenesis of BC cells via elevated pAkt signaling. Administration of YHD in vivo also strikingly repressed angiogenesis in tumor grafts. Conclusion: YHD could partially inhibit and reverse tumorigenesis of BC. It also could inhibit Akt activation and angiogenesis in vitro and in vivo. Its effect was superior to trastuzumab. Thus it was suitable for prevention and treatment of BC.

scholarly journals In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.

1989 ◽  
Vol 57 (6) ◽  
pp. 1800-1808 ◽  
Author(s):  
R E Garner ◽  
U Kuruganti ◽  
C W Czarniecki ◽  
H H Chiu ◽  
J E Domer
Keyword(s):  
Candida Albicans ◽  
Immune Responses ◽  
Gamma Interferon

DDRE-26. INHIBITION OF PRMT5 SENSITIZES GLIOBLASTOMA MODELS TO TRAMETINIB TREATMENT

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi79-vi80
Author(s):  
Yesh Banasavadi ◽  
Sriya Namagiri ◽  
yoshihiro Otani ◽  
Shilpa Thammegowda ◽  
Hannah Sur ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Survival Curve ◽  
Oral Gavage ◽  
Cycle Progression ◽  
Arginine Methyltransferase ◽  
Tumor Bearing ◽  
Nsg Mice ◽  
Kaplan Meier ◽  
Meier Survival Curve

Abstract With limited effective therapeutic strategies, the prognosis for glioblastoma (GBM) is very poor. Our previous study shows that the expression of Protein Arginine Methyltransferase 5 (PRMT5) is upregulated in GBM; its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. MEK inhibitors, including trametinib, are currently under investigation for GBM therapy. In this study, we tested whether inhibition of PRMT5 can enhance the anti-GBM efficacy of trametinib. Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot analysis were conducted. In vivo, PRMT5-intact and -depleted GBMNS were intracranially implanted in NSG mice and treated with trametinib by daily oral gavage, and tumor progression and mice survival rate were analyzed by MRI and Kaplan-Meier survival curve, respectively. Depletion of PRMT5 increased the cytotoxic effect of trametinib in GBMNS. Trametinib treatment increased the activity of ERBB3 and AKT; With PRMT5 knockdown, the activity of both AKT and ERBB3 decreased significantly. But, inhibition of ERBB3 alone failed to block the trametinib-induced AKT activity suggesting that even though PRMT5 regulates the activity of both ERBB3 and AKT, the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib treated GBMNS is because of AKT inhibition alone. In vivo, PRMT5-depletion extended the survival of the tumor-bearing mice that further increased in combination with trametinib treatment. Interestingly, trametinib treatment alone had no survival benefit.

scholarly journals IL-1 drives breast cancer growth and bone metastasis in vivo

Oncotarget ◽  
2016 ◽  
Vol 7 (46) ◽  
pp. 75571-75584 ◽  
Author(s):  
Ingunn Holen ◽  
Diane V. Lefley ◽  
Sheila E. Francis ◽  
Sarah Rennicks ◽  
Steven Bradbury ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Growth ◽  
Breast Cancer Growth

scholarly journals Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Exerts Anti-Breast Cancer Effect via miR-200c-PDE7B/PD-L1-AKT/MAPK Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yue Yang ◽  
Ting Fang ◽  
Yi-Lan Cao ◽  
Ya-Xin Lv ◽  
Qing-Qi Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ethyl Acetate ◽  
Colony Formation ◽  
Ethyl Acetate Fraction ◽  
Aqueous Extracts ◽  
Optimal Ratio ◽  
Hedyotis Diffusa ◽  
4T1 Cells

Background. Hedyotis diffusa (HD) Willd. and Scutellaria barbata (SB) D. Don in different ratios have been frequently used to treat various cancers in clinical Traditional Chinese Medicine prescriptions. However, the optimal ratio, active fraction, and molecular mechanisms associated with the anti-breast cancer role of this herbal couplet have not been elaborated. Methods. To screen out the optimal ratio of this herbal couplet, we compare aqueous extracts of HD, SB, or HD plus SB in different weight ratios (HS11, HS12, HS21) for their anticancer effects on murine breast cancer 4T1 cells in vitro and in vivo. EA11, the ethyl acetate fraction from HS11 (the aqueous extract of the couplet at an equal weight ratio), is further assessed for its antiproliferative effect as well as the antitumorigenic impact with the aid of immunocompetent mice. Colony formation, flow cytometry, western blot, ELISA, and qRT-PCR are used to elucidate mechanisms underlying EA11-led effects. Results. HS11 presents the most potential suppression of 4T1 cell proliferation and tumor growth among these aqueous extracts. The comparison results show that EA11 is more effective than HS11 in vitro and in vivo. EA11 inhibits colony formation and induces apoptosis in a concentration-dependent manner. EA11 reduces the protein expressions of PDE7B, PD-L1, β-catenin, and cyclin D1 while elevating the concentration of cellular cAMP and miR-200c expression in 4T1 cells. Additionally, EA11 exerts its anticancer effect partially via the inactivation of MAPK and AKT signaling pathways. Conclusions. This study implicates that EA11 prevents breast tumor development by interfering with the miR-200c-PDE7B/PD-L1-AKT/MAPK axis. EA11 may represent a potential therapeutic candidate for breast cancer.

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