scholarly journals Effect of Artemisia vulgaris Extract on Granzyme Expression and Tumor Mass Diameter (Study of Adriamycin Cyclophosphamide Chemotherapy in Adenocarcinoma Mammae C3H Mice Model)

2021 ◽  
Vol 31 (4) ◽  
pp. 1
Author(s):  
Gery Rifano Hardanto ◽  
Selamat Budijitno ◽  
Hardian Hardian

<p>Breast cancer incident continues to increase globally. The surgical management can be combined with other therapeutic modalities, including chemotherapy, radiation, and immunotherapy, such as Artemisia vulgaris (AV). This study aimed to determine the effect of AV extract on Granzyme expression and tumor mass diameter growth of C3H mice with adenocarcinoma mammae. Twenty-four female C3H mice were randomly divided into groups of K (control), P1 (AC chemotherapy), P2 (AV extract), and P3 (combination). Adenocarcinoma mammae were inoculated from donor mice. Two cycles of chemotherapy by Adriamycin 0.18 mg and Cyclophosphamide 1.8 mg were given intravenously, while Artemisia vulgaris 13 mg (0.2 ml) was given orally once per day. Granzyme expression was assessed using immunohistochemical staining, while tumor mass diameter growth was measured using tumor calipers. There was a significant negative correlation between and tumor mass diameter growth (p=0,001 and r=-0,911). Artemisia vulgaris increases the apoptotic effects of Adriamycin-Cyclophosphamide chemotherapy by increasing Granzyme expression and decreasing tumor mass diameter growth in adenocarcinoma mammae C3H mice.</p>

2021 ◽  
Vol 5 (7) ◽  
pp. 676-684
Author(s):  
Bayu Teguh Saputro ◽  
Selamat Budijitno

Introduction: Breast cancer is still a major health problem in the world. In the case of breast cancer, surgery is the main treatment option besides chemotherapy, radiation, and immunotherapy such as Artemisia vulgaris (AV). AV is cytotoxic selectively acts as a supplement to breast adenocarcinoma chemotherapy given the Adriamycin-Cyclophosphamide regimen, to improve chemotherapy response.The study was aimed to proving AV extract enhances the chemotherapy response in C3H mice with adenocarcinoma mammae given Adriamycin-Cyclophosphamide Chemotherapy. Method: This study used Post test only control group design on 24 females C3H mice that were randomly selected and divided into four groups: group K (control), P1 (chemotherapy), P2 (extract), and P3 (combination). Adenocarcinoma mammae comes from the inoculation of donor mice. Chemotherapy of Adriamycin 60 mg / m 2 and Cyclophosphamide 600 mg / m 2 were given in two cycles. AV 13 mg (0.2 ml) was given once daily orally. CD34 were evaluated by imunohistochemical staining and tumor mass diameter were counted by calipers. Result: The microvascular density CD34 and tumor mass diameter were obtained in groups of K, P1, P2, P3 respectively 60.76 ± 1.5; 39.70 ± 2.00; 57.10 ± 1.29; 35.26 ± 2.06 and 12.52 ± 1.49; 6.20 + 1.04; 9,94 + 1.21; 3.94 + 0.76. Statistical analysis showed significant differences in CD34 between groups K vs P1, P2, P3 (p = 0.001, p = 0.014, p = 0.001), P1 vs P2 and P3 (p = 0.001, p = 0.033) and P2 (P = 0.001). Tumor mass diameter between groups K vs P1, P2, P3 (p=0.001; p=0.014; p=0,001), P1 with P2 (p= 0.001) P1 with P3 (p = 0.033) and P2 with P3 (p = 0.001). Correlation analysis between CD34 with tumor mass diameter was found to have significant correlation (p = 0.001 and r = 0.932). Conclusion: Artemisia vulgaris is a potential to reduce angiogenesis in terms of decreasing the microvascular density CD34 and tumor mass diameter of adenocarcinoma mammae of C3H mice treated with Adriamycin-Cyclophosphamide chemotherapy and can improve the effectivity.


2021 ◽  
Vol 5 (3) ◽  
pp. 704-712
Author(s):  
Bayu Teguh Saputro ◽  
Selamat Budijitno

Introduction: Breast cancer is still a major health problem in the world. In the case of breast cancer, surgery is the main treatment option besides chemotherapy, radiation, and immunotherapy such as Artemisia vulgaris (AV). AV is cytotoxic selectively acts as a supplement to breast adenocarcinoma chemotherapy given the Adriamycin-Cyclophosphamide regimen, to improve chemotherapy response.The study was aimed to proving AV extract enhances the chemotherapy response in C3H mice with adenocarcinoma mammae given Adriamycin-Cyclophosphamide Chemotherapy. Method: This study used Post test only control group design on 24 females C3H mice that were randomly selected and divided into four groups: group K (control), P1 (chemotherapy), P2 (extract), and P3 (combination). Adenocarcinoma mammae comes from the inoculation of donor mice. Chemotherapy of Adriamycin 60 mg / m 2 and Cyclophosphamide 600 mg / m 2 were given in two cycles. AV 13 mg (0.2 ml) was given once daily orally. CD34 were evaluated by imunohistochemical staining and tumor mass diameter were counted by calipers. Result: The microvascular density CD34 and tumor mass diameter were obtained in groups of K, P1, P2, P3 respectively 60.76 ± 1.5; 39.70 ± 2.00; 57.10 ± 1.29; 35.26 ± 2.06 and 12.52 ± 1.49; 6.20 + 1.04; 9,94 + 1.21; 3.94 + 0.76. Statistical analysis showed significant differences in CD34 between groups K vs P1, P2, P3 (p = 0.001, p = 0.014, p = 0.001), P1 vs P2 and P3 (p = 0.001, p = 0.033) and P2 (P = 0.001). Tumor mass diameter between groups K vs P1, P2, P3 (p=0.001; p=0.014; p=0,001), P1 with P2 (p= 0.001) P1 with P3 (p = 0.033) and P2 with P3 (p = 0.001). Correlation analysis between CD34 with tumor mass diameter was found to have significant correlation (p = 0.001 and r = 0.932). Conclusion: Artemisia vulgaris is a potential to reduce angiogenesis in terms of decreasing the microvascular density CD34 and tumor mass diameter of adenocarcinoma mammae of C3H mice treated with Adriamycin-Cyclophosphamide chemotherapy and can improve the effectivity.


Background: The incidence of breast cancer worldwide is still high. Surgery remains the top choice with other modalities of chemotherapy, radiation, and suplementation such as Artemisia vulgaris (AV). Aim: The study was aimed to demonstrate that administration of AV extract decreased the expression of Cyclin-D1 and the expression of Ki-67 in adenocarcinoma mammae. Method: This study used “Posttest only control group design” on 24 females C3H mice that were randomly selected and divided into four groups: group K (control), P1 (chemotherapy), P2 (extract), and P3 (combination). Adenocarcinoma mammae comes from the inoculation of donor mice. Chemotherapy of Adriamycin 60 mg / m2 and Cyclophosphamide 600 mg / m2 were given in 2 cycles. AV 13 mg (0.2 ml) was given once daily orally. Cyclin-D1expression and Ki-67 expression were evaluated by imunohistochemical staining. Result: Mean of Cyclin-D1expression and Ki-67 expression were found in groups K, P1, P2, P3 were 35,30 + 0,72; 20,38 + 0,67; 33,50 + 0,71; 17,36 + 0,66; and 66,44 + 0,65; 35,40 + 0,65; 64,12 + 0,85; 32,32 + 0,61. The statistical analysis showed that there were significant differences in the expression of Cyclin-D1 between groups of K vs P1, P3 (p = 0,001), P1 vs P2 (p = 0,001), P1 vs P3 (p = 0,045), P2 vs P3 (p = 0,001), and in Ki-67 expression between groups of K vs P1, P3 (p = 0,001), P1 vs P2 (p = 0,001), P1 vs P3 (p = 0,041), P2 vs P3 (p = 0,001). Correlation analysis between Cyclin-D1 expression and Ki-67 expression showed significant correlation (p = 0,030 dan r = 0,914). Conclusion: Artemisia vulgaris is potential as supplementation that can improve the effectivity of AdriamycinCyclophosphamide chemotherapy in terms of decreased expression of Cyclin-D1 and expression of Ki-67 adenocarcinoma mammae of C3H mice.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meiou Dai ◽  
Gang Yan ◽  
Ni Wang ◽  
Girija Daliah ◽  
Ashlin M. Edick ◽  
...  

AbstractTriple negative breast cancer (TNBC) patients exhibit poor survival outcomes and lack effective targeted therapies. Using unbiased in vivo genome-wide CRISPR screening, we interrogated cancer vulnerabilities in TNBC and identified an interplay between oncogenic and tumor suppressor pathways. This study reveals tumor regulatory functions for essential components of the mTOR and Hippo pathways in TNBC. Using in vitro drug matrix synergy models and in vivo patient-derived xenografts, we further establish the therapeutic relevance of our findings and show that pharmacological inhibition of mTORC1/2 and oncoprotein YAP efficiently reduces tumorigenesis in TNBC. At the molecular level, we find that while verteporfin-induced YAP inhibition leads to apoptosis, torin1-mediated mTORC1/2 inhibition promotes macropinocytosis. Torin1-induced macropinocytosis further facilitates verteporfin uptake, thereby greatly enhancing its pro-apoptotic effects in cancer cells. Overall, our study underscores the power and robustness of in vivo CRISPR genome-wide screens in identifying clinically relevant and innovative therapeutic modalities in cancer.


2018 ◽  
Vol 15 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Aliny Aparecida Lopes Ribeiro ◽  
Fabiana Helen da Silva ◽  
Aron Carlos de Melo Cotrim ◽  
Alessandra Lima Deluque ◽  
Patricia Gelli Feres de Marchi ◽  
...  

2020 ◽  
Vol 20 (7) ◽  
pp. 790-799 ◽  
Author(s):  
Farnaz D. Moghaddam ◽  
Pejman Mortazavi ◽  
Somayeh Hamedi ◽  
Mohammad Nabiuni ◽  
Nasim H. Roodbari

Background and Purpose: Melittin, as the main ingredient of honeybee venom, that has shown anticancer properties. The present study aimed at investigating the cytotoxic impacts of melittin on 4T1 breast cancer cells. Methods: Hemolytic activity of different concentrations (0.125, 0.25, 0.5, 1, 2, 4, 8μg/ml) of melittin was assayed and then cytotoxicity of selected concentrations of melittin (2, 4, 8, 16, 32, and 64μg/ml), 2 and 4μg/ml of cisplatin and 0.513, 0.295 and 0.123μg/ml of doxorubicin was evaluated on 4T1 cells using MTT assay. We used Morphological evaluation and flow cytometric analysis was used. Real time PCR was also used to determine mRNA expression of Mfn1 and Drp1 genes. Results: All compounds showed anti-proliferative effects on the tumor cell line with different potencies. Melittin had higher cytotoxicity against 4T1 breast cancer cells (IC50= 32μg/ml-72h) and higher hemolytic activity (HD50= 1μg/ml), as compared to cisplatin and doxorubicin. Mellitin at 16 and 32μg/ml showed apoptotic effects on 4T1 cells according to the flow cytometric analysis. The Real time PCR analysis of Drp1 and Mfn1 expression in cells treated with 16μg/ml of melittin revealed an up-regulation in Drp1 and Mfn1 genes mRNA expression in comparison with control group. Treatment with 32μg/ml of melittin was also associated with a rise in mRNA expression of Drp1 and Mfn1 as compared to the control group. Conclusion: The results of this study showed that melittin has anticancer effects on 4T1 cell lines in a dose and time dependent manner and can be a good candidate for further research on breast cancer treatment.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Byunghee Yoo ◽  
Alana Ross ◽  
Pamela Pantazopoulos ◽  
Zdravka Medarova

AbstractRNA interference represents one of the most appealing therapeutic modalities for cancer because of its potency, versatility, and modularity. Because the mechanism is catalytic and affects the expression of disease-causing antigens at the post-transcriptional level, only small amounts of therapeutic need to be delivered to the target in order to exert a robust therapeutic effect. RNA interference is also advantageous over other treatment modalities, such as monoclonal antibodies or small molecules, because it has a much broader array of druggable targets. Finally, the complementarity of the genetic code gives us the opportunity to design RNAi therapeutics using computational, rational approaches. Previously, we developed and tested an RNAi-targeted therapeutic, termed MN-anti-miR10b, which was designed to inhibit the critical driver of metastasis and metastatic colonization, miRNA-10b. We showed in animal models of metastatic breast cancer that MN-anti-miR10b accumulated into tumors and metastases in the lymph nodes, lungs, and bone, following simple intravenous injection. We also found that treatment incorporating MN-anti-miR10b was effective at inhibiting the emergence of metastases and could regress already established metastases in the lymph nodes, lungs, and bone. In the present study, we extend the application of MN-anti-miR10b to a model of breast cancer metastatic to the brain. We demonstrate delivery to the metastatic lesions and obtain evidence of a therapeutic effect manifested as inhibition of metastatic progression. This investigation represents an additional step towards translating similar RNAi-targeted therapeutics for the systemic treatment of metastatic disease.


2002 ◽  
pp. 45-59 ◽  
Author(s):  
K W Colston ◽  
C M√∏rk Hansen

It is now well established that, in addition to its central role in the maintenance of extracellular calcium levels and bone mineralization, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, also acts as a modulator of cell growth and differentiation in a number of cell types, including breast cancer cells. The anti-proliferative effects of 1,25(OH)(2)D(3) have been linked to suppression of growth stimulatory signals and potentiation of growth inhibitory signals, which lead to changes in cell cycle regulators such as p21(WAF-1/CIP1) and p27(kip1), cyclins and retinoblastoma protein as well as induction of apoptosis. Such studies have led to interest in the potential use of 1,25(OH)(2)D(3) in the treatment or prevention of certain cancers. Since this approach is limited by the tendency of 1,25(OH)(2)D(3) to cause hypercalcaemia, synthetic vitamin D analogues have been developed which display separation of the growth regulating effects from calcium mobilizing actions. This review examines mechanisms by which 1,25(OH)(2)D(3) and its active analogues exert both anti-proliferative and pro-apoptotic effects and describes some of the synthetic analogues that have been shown to be of particular interest in relation to breast cancer.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nermin S. Ahmed ◽  
Marek Samec ◽  
Alena Liskova ◽  
Peter Kubatka ◽  
Luciano Saso

AbstractTamoxifen is the gold standard drug for the treatment of breast cancer in pre and post-menopausal women. Its journey from a failing contraceptive to a blockbuster is an example of pharmaceutical innovation challenges. Tamoxifen has a wide range of pharmacological activities; a drug that was initially thought to work via a simple Estrogen receptor (ER) mechanism was proven to mediate its activity through several non-ER mechanisms. Here in we review the previous literature describing ER and non-ER targets of tamoxifen, we highlighted the overlooked connection between tamoxifen, tamoxifen apoptotic effects and oxidative stress.


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