Antitumor effects of Auraptene in 4T1 tumor‐bearing Balb/c mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza. Shiran ◽  
Davar Amani ◽  
Abolghasem Ajami ◽  
Mahshad Jalalpourroodsari ◽  
Maghsoud Khalizadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Tumor Volume ◽  
Serum Levels ◽  
Ki 67 ◽  
Tumor Bearing ◽  
Paraffin Oil ◽  
Anti Cancer ◽  
Before And After ◽  
Ifn Γ

Abstract Objectives Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide. Methods In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels. Results There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment. Conclusions In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.

Psoralidin exerts anti-tumor, anti-angiogenic, and immunostimulatory activities in 4T1 tumor‐bearing balb/c mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Davar Amani ◽  
Elham Shakiba ◽  
Ehsan Motaghi ◽  
Hiva Alipanah ◽  
Mahshad Jalalpourroodsari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Serum Level ◽  
Tumor Volume ◽  
Treated Group ◽  
The Body ◽  
Ki 67 ◽  
Tumor Bearing ◽  
Anti Cancer ◽  
Ifn Γ

Abstract Background Psoralidin as a compound of the Psoralea corylifolia seeds exhibited several anti-cancer potentials in various cancers. Materials and methods In this study, 4T1 tumor‐bearing Balb/c mice were treated by intraperitoneal administration of Psoralidin, and Paraffin, as a control group to investigate anti-tumor, anti-angiogenic, and immunostimulatory activities in breast cancer. Body weight and tumor volume measurement were performed. Hematoxylin and Eosin (H&E) staining as well as immunohistochemistry for Ki-67, CD31 and VEGF markers were conducted. In addition, ELISA assay was performed for evaluating the serum level of IFN-γ and IL-4. Moreover, real time assay was performed to evaluate the expression of angiogenesis and immunostimulatory related genes. Results There were no significant changes in the body weight of all animal groups. The anti-cancer effects of Psoralidin were significantly observed after 24 days of the last treatment, confirmed by smaller tumor volume and also H&E staining. The expression level of Ki‐67, CD31 and VEGF were significantly decreased in tumor tissues of the Psoralidin-treated group in comparison with Paraffin-treated group. Moreover, there was a significant reduction in the serum level of IL-4 in tumor-bearing mice after Psoralidin treatment while the serum level of IFN-γ was significantly augmented in all groups. Moreover, the reduction in expression of VEGF-a and IL-1β was observed. Interestingly Psoralidin treatment led to expression increase of FOXp3. Conclusions Psoralidin shows the anti-cancer potential in an animal model of breast cancer; however, further studies are recommended to elucidate its mechanisms of action.

Zingerone improves the immune responses in an animal model of breast cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Modje Kazemi ◽  
Abdollah Jafarzadeh ◽  
Maryam Nemati ◽  
Fereshteh Taghipour ◽  
Omolbanin Oladpour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Animal Model ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Hemagglutination Assay ◽  
Tumor Bearing ◽  
Anti Cancer ◽  
Ifn Γ ◽  
After Cancer

Abstract Objectives The potent anti-tumorigenic effects were attributed to ginger and there are some reports regarding the anti-cancer and immunomodulatory properties ginger-derived components. This study aimed to investigate the effects of zingerone on some immune-related parameters in an animal model of breast cancer. Methods The breast cancer was established in female BALB/c mice using a carcinogenic 4T1 cell line. At day 10 after cancer induction, tumor-bearing mice were divided into five groups and treated intraperitoneal (daily from days 11–30) with saline or zingerone (at doses 10, 20, 50 and 100 mg/kg/day). The mice were sacrificed on day 31 and the number of splenic Th1- and Treg cells, the expression of IFN-γ and TGF-β in the blood mononuclear cells, the antibody production against sheep red blood cell (SRBC) were determined using flow cytometry, real time-PCR and a standard hemagglutination assay, respectively. Results Zingerone at doses 50 and 100 mg/kg enhanced the number of splenic Th1 cells (p<0.03 and 0.007, respectively); at doses 10, 20, 50 and 100 mg/kg reduced the number of splenic Treg cells (p<0.02, 0.01, and 0.01, respectively), at doses 50 and 100 mg/kg enhanced the expression of IFN-γ (p<0.03), at doses 50 and 100 mg/kg reduced the expression of TGF-β, at doses 50 mg/kg reduced the titer of anti-SRBC antibody (p<0.05). Conclusions Zingerone improve the T cell-mediated and antibody responses in a mouse model of breast cancer. The immunotherapeutic potentials of zingerone in cancers need more considerations.

The Effect of Sirtuin 2 (Sirt2) Overexpressing Bone Marrow Mesenchymal Stem Cells on the Growth of Human Epidermal Growth Factor Receptor 2 (Her-2) Breast Cancer Cells and Its Mechanism

2021 ◽  
Vol 11 (4) ◽  
pp. 778-785
Author(s):  
Xiaolin Chen ◽  
Yan Wang ◽  
Sunlu Jiang
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Nk Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Caspase 3 ◽  
Tumor Bearing ◽  
Her 2 ◽  
Ifn Γ

Our study investigates the effect of high expression of Sirt2 in MSCs (MSCs-Sirt2) on Her-2 breast cancer cell proliferation. A mouse subcutaneous xenograft tumor model was established and MSCssirt2 analysis was performed on nude mice. TUNEL staining, flow cytometry, western-blot, real-time PCR and immunohistochemistry were used to detect cancer cell apoptosis. The number of NK cells infiltrated by flow cytometry detected the tumor tissue of tumor-bearing mice, and its killing activity on tumor-bearing mice was detected by isotope labeling and release method. The levels of TNF-α, IFN-γ, IL-8, IL-6 and IL-10 were detected by ELISA. Caspase-3 level was decreased in the MSCs group (P <0.01) while increased in the MSCs-sirt2 group (P <0.001). However, PCNA expression showed an opposite profile in the Her-2 group and MSCs-sirt2 group compared to Caspase-3 level (P <0.01). The tumor volume and weight in the MSCs-sirt2 group was significantly reduced (P < 0.01), while increased in the MSCs group significantly (P < 0.05). The number of Ki-67-positive tumor cells in MSCs-sirt2 group was significantly reduced (P <0.01) and increased in MSCs group (P < 0.001) with oppositive number of TUNEL-positive tumor cells in the MSCs-sirt2 group and MSCs group (P <0.01). IFN-γ level showed an upward trend (P <0.001). The NK cell toxicity of MSCs-Sirt2 group was significantly higher (P <0.001). MSCs-Sirt2 has an inhibitory effect on Her-2 breast cancer cell growth by enhancing the local inflammatory response of NK cells.

Correlation between Changes in Prolactin and Melatonin Serum Levels after Radical Mastectomy

1987 ◽  
Vol 73 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Paolo Lissoni ◽  
Franco Paolorossi ◽  
Sandro Barni ◽  
Gabriele Tancini ◽  
Sergio Crispino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Stage ◽  
Radical Mastectomy ◽  
Serum Levels ◽  
Axillary Node ◽  
Neoplastic Disease ◽  
Before And After ◽  
Node Involvement ◽  
Breast Cancer Growth ◽  
The Relationship

Both prolactin (PRL) and melatonin (MLT) (the most important pineal hormone) have been shown to play a role in regulating breast cancer growth. The present study was carried out to investigate the relationship between PRL and MLT secretions in human breast cancer. Twenty-four women with breast cancer, at clinical stage T1-2 N0-2 M0, were evaluated before and after radical mastectomy. As controls, 14 women who underwent surgery for reasons other than neoplastic disease were included in the study. PRL and MLT serum levels were measured by RIA before and 15 days after surgery. There were no significant differences in mean PRL serum levels between patients and controls; mean MLT serum values were significantly higher in patients than in controls. In no control subject was PRL affected by surgery. In contrast, 13/24 breast cancer women showed high PRL levels after mastectomy; the PRL rise induced by surgery was significantly higher in patients without axillary node involvement. MLT was not affected by mastectomy in 13 patients, whereas it was enhanced in 5 women and decreased in the last 6 cases. No significant correlation was seen between PRL and MLT changes induced by mastectomy. The present study shows that radical mastectomy influences PRL and MLT secretions, however, its clinical significance remains to be established.

scholarly journals Regulation of Parathyroid Hormone-Related Peptide by Estradiol: Effect on Tumor Growth and Metastasis in Vitro and in Vivo

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 2885-2894 ◽  
Author(s):  
S. A. Rabbani ◽  
P. Khalili ◽  
A. Arakelian ◽  
H. Pizzi ◽  
G. Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Tumor Growth ◽  
Tumor Volume ◽  
In Vivo Studies ◽  
Promoting Effect ◽  
X Ray ◽  
Tumor Bearing ◽  
Tumor Growth And Metastasis

Abstract We evaluated the capacity of estradiol (E2) to regulate PTHrP production, cell growth, tumor growth, and metastasis to the skeleton in breast cancer. In estrogen receptor (ER)-negative human breast cancer cells, MDA-MB-231, and cells transfected with full-length cDNA encoding ER (S-30), E2 caused a marked decrease in cell growth and PTHrP production, effects that were abrogated by anti-E2 tamoxifen. E2 also inhibited PTHrP promoter activity in S-30 cells. For in vivo studies, MDA-MB-231 and S-30 cells were inoculated into the mammary fat pad of female BALB/c nu.nu mice. Animals receiving S-30 cells developed tumors of significantly smaller volume compared with MDA-MB-231 tumor-bearing animals. This change in tumor volume was reversed when S-30 cells were inoculated into ovariectomized (OVX) hosts. Inoculation of MDA-MB-231 cells into the left ventricle resulted in the development of lesions in femora and tibia as determined by x-ray analysis. In contrast, these lesions were significantly smaller in volume and number in animals inoculated with S-30, and this lower incidence was reversed in OVX animals. Bone histological analysis showed that the tumor volume to tissue volume ratio was comparable with that seen by x-ray. Immunohistochemical analysis showed that PTHrP production was inhibited in S-30 group and restored to levels comparable to that seen in MDA-MB-231 tumor-bearing animals when S-30 cells were inoculated in OVX animals. Collectively these studies show that E2 production is inversely correlated with PTHrP production and that the growth-promoting effect of PTHrP has a direct impact on tumor growth at both nonskeletal and skeletal sites.

Phase II study of goserelin for patients with postmenopausal metastatic breast cancer.

1993 ◽  
Vol 11 (8) ◽  
pp. 1529-1535 ◽  
Author(s):  
T Saphner ◽  
A B Troxel ◽  
D C Tormey ◽  
D Neuberg ◽  
N J Robert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Response Rate ◽  
Single Agent ◽  
Metastatic Breast ◽  
Postmenopausal Breast Cancer ◽  
Complete Response ◽  
Serum Levels ◽  
Breast Cancer Patients ◽  
Before And After

PURPOSE To determine the response rate of postmenopausal breast cancer patients to the gonadotropin-releasing hormone (GN-RH) agonist, Zoladex (goserelin; ICI Pharma, Wilmington, DE). PATIENTS AND METHODS A multi-institutional single-agent trial in postmenopausal patients was conducted. Serum levels of follicle-stimulating hormone (FSH), testosterone, and estradiol were requested before and after Zoladex treatment. RESULTS For estrogen receptor-positive (ER+) patients, the response rate was 11%, with one complete response (CR) and three partial responses (PRs) among 36 eligible patients. Responses were of short duration. There were no responses among 16 estrogen receptor-negative (ER-) patients. CONCLUSION GN-RH agonists have activity in ER+ postmenopausal patients, but response rates are not as high as with other available endocrine therapies and the duration of response is short.

scholarly journals Serum levels of selenium in patients with breast cancer before and after treatment of external beam radiotherapy

2011 ◽  
Vol 22 (5) ◽  
pp. 1109-1112 ◽  
Author(s):  
C.A.S. Franca ◽  
C.R. Nogueira ◽  
A. Ramalho ◽  
A.C.P. Carvalho ◽  
S.L. Vieira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
External Beam Radiotherapy ◽  
Serum Levels ◽  
External Beam ◽  
Before And After

CD11b− Donor Dendritic Cells Enhance Donor T-Cells’ Th1 Polarization and Graft Versus Leukemia Activity in Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1252-1252 ◽  
Author(s):  
Jian-Ming Li ◽  
Kataryna A. Darlak ◽  
Ying Lu ◽  
Cynthia Giver ◽  
Wayne Harris ◽  
...  
Keyword(s):  
T Cells ◽  
Serum Levels ◽  
Hematopoietic Stem ◽  
Treatment Groups ◽  
Post Transplant ◽  
Tumor Bearing ◽  
Donor T Cells ◽  
Ifn Γ ◽  
Th1 Cytokines

Abstract Background: Based on a clinical association of donor plasmacytoid dendritic cell (DC) content with leukemia relapses after allogeneic BMT (Waller, Blood 2001), we have previously reported that CD11b− donor DC added to a graft containing FACS-purified hematopoietic stem cells (HSC) and T-cells enhanced interferon-γ (IFN-γ) production and GvL activity in MHC-mismatched allogeneic transplant mouse models (Li, Blood 2007). Objective: In this study, we studied the mechanisms whereby donor DC in the graft modulate donor T-cell activity and the graft-versus-leukemia (GvL) effect in MiHA (C3H.SW → C57BL/6J)- and MHC (C57BL/6J → B10.BR)- mismatched models of allogeneic hematopoietic stem cell transplantation (HSCT). Methods: Mice irradiated to 11 Gy received 5 × 104 log-phase viable MMB3.19 myeloid lymphoma cells via intraperitoneal injection or intravenous injection of 1 x 105 LBRM T-cell lymphoma cells one day before transplant. Allografts consisted of 5 × 104 FACS-purified donor BM CD11b− DC or CD11b+ DC plus 3 × 103 FACS-purified c-kit+ sca-1+ lineage− hematopoietic stem cells (HSC) in combination with either 3 × 105 T-cells, 3 × 105 CD8+ T-cells or no additional T-cells transplanted via tail vein. Graft-versus-host disease (GvHD) clinical scores (based on body weight loss, posture, skin, fur texture, activity) were recorded twice weekly in non-tumor bearing recipients. In vitro proliferation and cytotoxic activity of donor-derived T-cells against tumor targets was assessed by CFSE staining and a caspase flow cytometry assay (CyToxiLux PLUS) using donor T-cells harvested from recipients on day 34 and day 82 post transplant. Serum and intracellular Th1 cytokines (IFN-γ, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, and IL-10) from recipients’ peripheral blood and spleens day 3 and day 10 post-transplant was measured by ELISA and flow cytometry. IFN-γ direct killing of leukemia cells was tested by in vitro IFN-γ exposure. Results: In non-tumor bearing mice, recipients of all combinations of donor DC subsets, with and without donor T-cells had equivalent survival (75% – 85%) at 3 months post transplant without significant clinical signs of GvHD. Transplantation of tumor cells to recipients of HSC alone, HSC plus donor T-cells, or HSC plus T-cells and CD11b+ DC in the MiHA- and the MHC-mismatched transplant models led to 0% or 5% 3 month survival, respectively. Strikingly, tumor-bearing mice transplanted with CD11b− DC had significantly enhanced 3 month survival (35% in the MiHA-mismatched model and 45% in the MHCmismatched model) without increased GvHD (p&lt;0.001). There was no significant difference in survival between mice that received HSC plus CD11b− DC and a mixture of CD4+ and CD8+ donor T-cells versus mice that received HSC plus CD11b− DC and only CD8+ donor T-cells. Donor T-cells harvested from recipients of CD11b− DC 34 days after transplant in the MiHA-mismatched model as well as 82 days after transplant in the MHC-mismatched model displayed increased cell proliferation following co-culture with irradiated hosttype splenocytes as a source of alloantigen compared with donor T-cells harvested from recipients of CD11b+ DC or recipients of HSC plus T-cells without donor DC. Leukemia cell killing was greater following incubation of purified donor T-cells recovered from recipients of CD11b− DC with tumor targets compared to T-cells recovered from other treatment groups. Recipients of CD11b− DC had higher serum levels of Th1 cytokines IFN-γ and IL-2 and higher number of Th1 positive donor T-cells compared with recipients of other treatment groups. In contrast, recipients of CD11b+ DC had higher serum levels of Th2 cytokines IL-4, IL-5, and IL-10 and higher number of Th2 positive donor T-cells. IFN-γ added to in vitro cultures with MMB3.19, and LBRM, had no direct cell killing effect. Conclusion: CD11b− donor DC enhanced Th1 polarization of donor T-cells and GvL without increasing GvHD. Donor CD8+ T-cells mediated tumor killing effect. CD11b+ donor DC enhanced Th2 polarization of donor CD4+ T-cells and led to limited GvHD and GvL.

Phase II breast cancer chemoprevention study with celecoxib in women at increased risk for breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1010-1010
Author(s):  
B. Arun ◽  
V. Valero ◽  
G. Yin ◽  
G. Babiera ◽  
J. L. Murray ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Atypical Hyperplasia ◽  
Post Treatment ◽  
Short Term ◽  
Ki 67 ◽  
High Risk Women ◽  
Before And After ◽  
The Difference ◽  
Er Expression

1010 Background: Short-term chemoprevention trials offer a convenient model to screen chemopreventive agents and identify endpoint biomarkers. One of the potential agents is celecoxib (C), which has antiproliferative and apoptosis inducing properties. In this prospective study, our primary aim was to evaluate changes in proliferation induced by C in breast tissue of high risk women. Here, we report changes in estrogen receptor (ER) proliferation index. Methods: 42 eligible high risk women were enrolled into the study, underwent fine needle aspiration (FNA) and started celecoxib treatment at 400 mg BID. Median age: 51.9 years. Risk factors: Gail risk > 1.67% (n=13), lobular carcinoma insitu (n=13), atypical hyperplasia (n=11), previous history of breast cancer (n=5). For ER and Ki-67 testing, thin preparations slides were incubated with primary mouse monoclonal antibody 6F11 against the ER and clone MIB-1, respectively. Appropriate negative and positive controls were included. At least 100 epithelial cells were evaluated per slide. Immunoreactivity for each marker was scored as the percentage of positive nuclei. We assessed the difference in ER and Ki-67 levels before and after treatment using a Wilcoxon signed rank test. Results: The average pre-treatment ER expression in FNA samples was 35.9% and Ki-67 was 2.4%. 19 (45%) showed hyperplasia or atypical hyperplasia. 39 patients underwent also post-treatment FNAs. The pre-and post treatment ER expression in this group was 35.7% (range 0–100%) and 27.4% (range: 0–100%), respectively. The difference in ER levels was statistically significant (p = 0.04). Twenty-six patients had Ki-67 levels measured both before and after treatment. The median difference in Ki-67 levels was 0 (range 0- 5). This change was not statistically significant (p = 0.63). Conclusions: We have completed accrual to a prospective short-term chemoprevention trial with celecoxib. We have found a significant downregulation of ER expression with 6 months celecoxib. Since ER expression is a marker of proliferation, this finding confirms celecoxibs antiproliferative properties. Currently, we have not observed a change in Ki-67; this could be partly due to the small number of samples and the fact that Ki-67 is low in normal epithelium. [Table: see text]

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