scholarly journals Immunological Characteristics between αβ TDC and γδ TDC Cells in the Spleen of Breast Cancer-Induced Mice

2021 ◽  
Vol 43 (05) ◽  
pp. 368-373
Author(s):  
Polyana Barbosa Silva ◽  
Márcia Antoniazi Michelin ◽  
Millena Prata Jammal ◽  
Eddie Fernando Cândido Murta
Keyword(s):  
Breast Cancer ◽  
Tumor Cell Line ◽  
Experimental Period ◽  
Cell Types ◽  
System Response ◽  
Control Group ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line ◽  
Tnf Α ◽  
Ifn Γ

Abstract Objective To evaluate the antitumoral role of γδ TDC cells and αβ TDC cells in an experimental model of breast cancer. Methods Thirty female Balb/c mice were divided into 2 groups: control group (n = 15) and induced-4T1 group (n = 15), in which the mice received 2 × 105 4T1 mammary tumor cell line. Following the 28-day experimental period, immune cells were collected from the spleen and analyzed by flow cytometry for comparison of αβ TDC (TCRαβ+ CD11c+MHCII+) and γδ TDC (TCRγδ+CD11c+MHCII+) cells regarding surface markers (CD4+ and C8+) and cytokines (IFN-γ, TNF-α, IL-12 and IL-17). Results A total of 26.53% of γδ TDC - control group (p < 0.0001) - the proportion of αβ TDC was lower in splenic cells than γδ TDC; however, these 2 cell types were reduced in tumor conditions (p < 0.0001), and the proportion of IFN-γ, TNF-α, IL-12 and IL-17 cytokines produced by γδ TDC was higher than those produced by αβ TDC, but it decreased under conditions of tumor-related immune system response (p < 0.0001). Conclusion Healthy mice engrafted with malignant cells 4T1 breast tumor presented TDC with γδ TCR repertoire. These cells express cytotoxic molecules of lymphocytes T, producing anti-tumor proinflammatory cytokines.

scholarly journals Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line

2020 ◽  
Vol 21 (4) ◽  
pp. 1185
Author(s):  
Lilla Hámori ◽  
Gyöngyi Kudlik ◽  
Kornélia Szebényi ◽  
Nóra Kucsma ◽  
Bálint Szeder ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Mammary Tumor ◽  
Triple Negative ◽  
Tumor Cell Line ◽  
Breast Cancers ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line ◽  
Mouse Mammary Tumor ◽  
Mouse Mammary Tumor Cell

Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. By the age of 80, the estimated risk for breast cancer for women with germline BRCA1 or BRCA2 mutations is around 80%. Genetically engineered BRCA1-deficient mouse models offer a unique opportunity to study the pathogenesis and therapy of triple negative breast cancer. Here we present a newly established Brca1−/−, p53−/− mouse mammary tumor cell line, designated as CST. CST shows prominent features of BRCA1-mutated triple-negative breast cancers including increased motility, high proliferation rate, genome instability and sensitivity to platinum chemotherapy and PARP inhibitors (olaparib, veliparib, rucaparib and talazoparib). Genomic instability of CST cells was confirmed by whole genome sequencing, which also revealed the presence of COSMIC (Catalogue of Somatic Mutations in Cancer) mutation signatures 3 and 8 associated with homologous recombination (HR) deficiency. In vitro sensitivity of CST cells was tested against 11 chemotherapy agents. Tumors derived from orthotopically injected CST-mCherry cells in FVB-GFP mice showed sensitivity to cisplatin, providing a new model to study the cooperation of BRCA1-KO, mCherry-positive tumor cells and the GFP-expressing stromal compartment in therapy resistance and metastasis formation. In summary, we have established CST cells as a new model recapitulating major characteristics of BRCA1-negative breast cancers.

scholarly journals SAT-137 The Effect of Hypertriglyceridemia on Triple Negative Breast Cancer Progression

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tiffany Scully ◽  
Annie James ◽  
Chifei Kang ◽  
Irini M Antoniou ◽  
Abora Ettela ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Cancer Risk ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Cell Line ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line ◽  
The Metabolic Syndrome

Abstract Obesity is associated with increased cancer risk and cancer-associated mortality1,2. Hypertriglyceridemia (HTG), a component of the metabolic syndrome which frequently co-exists with obesity, has been associated with increased breast cancer risk and mortality in triple negative breast cancer (TNBC)3,4. To determine if HTG is causally related to enhanced TNBC progression in the absence of other obesity-associated characteristics, TNBC growth and metastasis in a mouse model of HTG was examined. Mice overexpressing human apolipoprotein C3 (AC3) were backcrossed onto FVB/N background and crossed with recombination-activating gene 1 (Rag1) knockout mice to generate immunodeficient HTG mice. AC3 mice relative to wild-type (WT) littermates showed a 20-fold higher circulating triglycerides (p &lt; 0.0001) and elevated very low density lipoprotein (VLDL) cholesterol (p = 0.001). No differences in body weight, body composition, blood glucose or plasma insulin levels were observed between the two groups, allowing for investigation on the influence of HTG on TNBC without confounders such as hyperinsulinemia or hyperglycemia. AC3 mice orthotopically implanted with the mouse mammary tumor cell line, Mvt1, showed both increased tumor growth (AC3 vs WT: 1157.0 ± 84.2 vs 707.2 ± 58.6 mm3, p = 0.0009) and lung metastasis (AC3 vs WT: 57.3 ± 3.0 vs 32.9 ± 5.3 mm3, p = 0.001) relative to WT mice. Immunodeficient Rag1/AC3 mice likewise, showed increased tumor growth compared to WT controls when implanted with human TNBC MDA-MB-231 cells (AC3 vs WT: 363.2 ± 113.9 vs 92.95 ± 16.2 mm3, p = 0.038). To investigate how HTG affects tumor lipid metabolism, serum and tumors from both groups were analyzed by liquid chromatography/mass spectrometry. Total alkyl-acyl, di-acyl-phosphatidylcholines and sphingomyelin concentrations were higher in the serum of AC3 mice relative to WT. In contrast, no overall difference in tumor phospholipid or acylcarnitine content was noted between AC3 and WT mice, suggesting no difference in fatty acid oxidation in the setting of HTG. Mvt1 tumors from AC3 and WT mice were analyzed by RNA sequencing. Decreased expression of genes associated with cholesterol synthesis (Fdft1, Pvmk, Acss2) were found in tumors from AC3 mice. Tumors from AC3 mice also showed decreased protein expression of LDLR, which is associated with LDL cholesterol uptake. Overall, these findings suggest that HTG, independently of other obesity-associated characteristics such as hyperinsulinemia and hyperglycemia, leads to changes in intracellular lipid metabolism and promotes TNBC progression. References: 1Chan, D. S. M. et al. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol.25, 1901-1914 (2014). 2Pierobon, M. & Frankenfeld, C. L. Breast Cancer Res. Treat.137, 307-314 (2013). 3Lofterød, T. et al. BMC Cancer18, 654 (2018).4Goodwin, P. J. et al. Nutr. Cancer27, 284-292 (1997).

scholarly journals Chemo-treated 4T1 breast cancer cells radiation response measured by single and multiple cell ionization using infrared laser trap

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Endris Muhammed ◽  
Li Chen ◽  
Ying Gao ◽  
Daniel Erenso
Keyword(s):  
Cancer Cells ◽  
Tumor Cell Line ◽  
Radiation Sensitivity ◽  
Infrared Laser ◽  
Control Group ◽  
Mammary Tumor Cell ◽  
Mammary Tumor Cell Line ◽  
4T1 Breast Cancer ◽  
The Individual ◽  
Multiple Cells

AbstractWe present a study that uses a laser trapping technique for measurement of radiation sensitivity of untreated and chemo-treated cancer cells. We used a human mammary tumor cell line (4T1) treated by an antitumor compound, 2-Dodecyl-6-methoxycyclohexa-2, 5-diene-1,4-dione (DMDD), which was extracted from the root of Averrhoa carambola L. The untreated control group, and both 2-hour and 24-hour treated groups of 4T1 cells were used in this study. The absorbed threshold ionization energy (TIE) and the threshold radiation dose (TRD) were determined using a high-power infrared laser (at 1064 nm) trap by single and multiple cells trapping and ionization. The results were analyzed using descriptive and t-statistics. The relation of the TIE and TRD to the mass of the individual cells were also analyzed for different hours of treatment in comparison with the control group. Both TIE and TRD decrease with increasing treatment periods. However, the TRD decreases with mass regardless of the treatment. Analyses of the TRD for single vs multiple cells ionizations within each group have also consistently showed this same behavior regardless of the treatment. The underlying factors for these observed relations are explained in terms of radiation, hyperthermia, and chemo effects.

scholarly journals High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 527
Author(s):  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Norma A. Téllez-Navarrete ◽  
Mario Preciado-García ◽  
Dámaris P. Romero-Rodríguez ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Control Group ◽  
Hiv Patients ◽  
Art Initiation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Α Level ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

scholarly journals Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

2010 ◽  
Vol 43 (4) ◽  
pp. 393-395 ◽  
Author(s):  
Kleber Giovanni Luz ◽  
Felipe Francisco Tuon ◽  
Maria Irma Seixas Duarte ◽  
Guilherme Mariz Maia ◽  
Paulo Matos ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Visceral Leishmaniasis ◽  
Intestinal Bacteria ◽  
Duodenal Mucosa ◽  
Control Group ◽  
Tnf Α ◽  
Organ Specific ◽  
Ifn Γ

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

scholarly journals Insulin Resistance and Inflammation in Black Women with and without Breast Cancer: Cause for Concern

2016 ◽  
Vol 26 (4) ◽  
pp. 513 ◽  
Author(s):  
Kathleen A. Griffith ◽  
Seon Yoon Chung ◽  
Shijun Zhu ◽  
Alice S. Ryan
Keyword(s):  
Breast Cancer ◽  
Insulin Resistance ◽  
Black Women ◽  
White Women ◽  
Cancer Recurrence ◽  
Control Group ◽  
Study Objective ◽  
Increased Risk ◽  
Tnf Α ◽  
History Of

<p class="Pa7"><strong>Objective: </strong>After chemotherapy for breast cancer, Black women gain more weight and have an increased mortality rate compared with White women. Our study objective was to compare biomarkers associated with obesity in Black women with and without a history of breast cancer.</p><p class="Pa7"><strong>Design: </strong>Case-control</p><p class="Pa7"><strong>Setting: </strong>Academic/federal institution</p><p class="Pa7"><strong>Participants: </strong>Black women with a history of breast cancer (cases) and age-matched controls.</p><p class="Pa7"><strong>Methods: </strong>We compared insulin resistance, inflammation, and lipids in overweight and obese Black women with a history of breast cancer (n=19), age similar controls (n=25), and older controls (n=32). Groups did not differ on mean body mass index (BMI), which was 35.4 kg/m2, 36.0 kg/m2, and 33.0 kg/m2, respectively.</p><p class="Default"><strong>Main Outcome Measures: </strong>Insulin resis­tance (HOMA-IR); inflammation (TNF-α, IL-1b, IL-6, IL-8, CRP); lipids (cholesterol, triglycerides).</p><p class="Pa7"><strong>Results: </strong>Cases had 1.6 and 1.38 times higher HOMA-IR values compared with age similar and older controls, respectively (P≤.001 for both). TNF-α and IL-1b were significantly higher in cases compared with both control groups (P&lt;.001 for both). IL-6 was also higher in cases compared with age-similar controls (P=.007), and IL-8 was lower in cases compared with older controls (P&lt;.05). Lipids did not differ between cases and either control group.</p><p class="Default"><strong>Conclusions: </strong>Black women with breast cancer were significantly more insulin resis­tant with increased inflammation compared not only with age similar controls but with women who were, on average, a decade older. These biomarkers of insulin resistance and inflammation may be associated with increased risk of breast cancer recurrence and require ongoing evaluation, especially given the relatively abnormal findings com­pared with the controls in this underserved group. <em></em></p><p class="Default"><em>Ethn Dis. </em>2016;26(4):513-520; doi:10.18865/ed.26.4.513</p>

scholarly journals Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Zuchao Cai ◽  
David Lim ◽  
Guochao Liu ◽  
Chen Chen ◽  
Liya Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Valproic Acid ◽  
Tumor Recurrence ◽  
Early Stage ◽  
Low Cost ◽  
Inhibit Tumor Growth ◽  
Tnf Α ◽  
M1 Phenotype ◽  
Ifn Γ ◽  
Concurrent Cancer

Inadequate sustained immune activation and tumor recurrence are major limitations of radiotherapy (RT), sustained and targeted activation of the tumor microenvironment can overcome this obstacle. Here, by two models of a primary rat breast cancer and cell co-culture, we demonstrated that valproic acid (VPA) and its derivative (HPTA) are effective immune activators for RT to inhibit tumor growth by inducing myeloid-derived macrophages and polarizing them toward the M1 phenotype, thus elevate the expression of cytokines such as IL-12, IL-6, IFN-γ and TNF-α during the early stage of the combination treatment. Meanwhile, activated CD8+ T cells increased, angiogenesis of tumors is inhibited, and the vasculature becomes sparse. Furthermore, it was suggested that VPA/HPTA can enhance the effects of RT via macrophage-mediated and macrophage-CD8+ T cell-mediated anti-tumor immunity. The combination of VPA/HPTA and RT treatment slowed the growth of tumors and prolong the anti-tumor effect by continuously maintaining the activated immune response. These are promising findings for the development of new effective, low-cost concurrent cancer therapy.

scholarly journals Glutamine modifies immune responses of mice infected with porcine circovirus type 2

2013 ◽  
Vol 110 (6) ◽  
pp. 1053-1060 ◽  
Author(s):  
Wenkai Ren ◽  
Yinghui Li ◽  
Xinglong Yu ◽  
Wei Luo ◽  
Gang Liu ◽  
...  
Keyword(s):  
Experimental Period ◽  
Porcine Circovirus Type ◽  
Virus Genome ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Glutamine Supplementation ◽  
Control Group ◽  
Protein Levels ◽  
Ifn Γ

The present study was conducted to evaluate the immune-enhancing effects of dietaryl-glutamine supplementation in porcine circovirus type 2 (PCV2)-infected mice, and to examine the clearance effects of glutamine against PCV2 in experimentally infected mice. A total of sixty Kunming female mice were infected with PCV2 at a dose of 100 TCID50(50 % tissue culture infection dose) by intraperitoneal injection after 2 weeks of dietaryl-glutamine supplementation orl-alanine supplementation (as the control (isonitrogenous) group). The measured variables on 3rd, 5th, 7th, 9th and 11th d post-infection (dpi) included: (1) PCV2 virus loaded in the liver, spleen, heart, lung, kidney, ovary and serum was determined by real-time PCR; (2) IL-2, IL-6, IL-10, interferon (IFN)-α, IFN-γ and C-reactive protein levels in serum were measured by ELISA; (3) serum total superoxide dismutase activity was measured spectrophotometrically at 550 nm absorbance. Dietaryl-glutamine supplementation significantly increased serum IL-2 levels on the 3rd (P< 0·01), 5th (P< 0·01), 7th (P< 0·05) and 9th dpi, significantly (P< 0·05) increased serum IL-6 levels on 3rd dpi, significantly (P< 0·05) increased serum IFN-γ levels on the 9th and 11th dpi and significantly decreased (P< 0·01) serum IL-10 levels on the 9th and 11th dpi, compared with those in the control group. Meanwhile, the PCV2 virus genome was detected sporadically throughout the experimental period in both groups. Taken together, the present results suggest that dietaryl-glutamine supplementation enhances immune function in PCV2-infected mice.

Sign in / Sign up

Export Citation Format

Share Document