scholarly journals Differential Impact of Calcitriol and Its Analogs on Tumor Stroma in Young and Aged Ovariectomized Mice Bearing 4T1 Mammary Gland Cancer

2020 ◽  
Vol 21 (17) ◽  
pp. 6359 ◽  
Author(s):  
Artur Anisiewicz ◽  
Agata Pawlik ◽  
Beata Filip-Psurska ◽  
Joanna Wietrzyk

(1) Background: Vitamin D compounds (VDC) are extensively studied in the field of anticancer properties, including breast cancer. Previously, we showed that calcitriol and its analogs (PRI-2191 and PRI-2205) stimulate metastasis in 4T1 murine mammary gland cancer models in young mice, whereas the reverse effect was observed in aged ovariectomized (OVX) mice; (2) Methods: We determined the phenotype of monocytes/macrophages using FACS and examined the expression of selected genes and proteins by Real-Time PCR and ELISA; (3) Results: Activities of VDC are accompanied by an increase in the percentage of Ly6Clow anti-inflammatory monocytes in the spleen of young and a decrease in aged OVX mice. Treatment of young mice with VDC resulted in an increase of CCL2 plasma and tumor concentration and Arg1 in tumor. In later stage of tumor progression the expression of genes related to metastasis in lung tissue was decreased or increased, in old OVX or young mice, respectively; (4) Conclusions: Pro- or anti-metastatic effects of calcitriol and its analogs in young or aged OVX mice, respectively, can be attributed to the differences in the effects of VDC on the tumor microenvironment, as a consequence of differences in the immunity status of young and aged mice.

2018 ◽  
Vol 15 (11) ◽  
pp. 5277-5290 ◽  
Author(s):  
Kseniia Porshneva ◽  
Diana Papiernik ◽  
Mateusz Psurski ◽  
Marcin Nowak ◽  
Rafał Matkowski ◽  
...  

2019 ◽  
Vol 61 (3) ◽  
pp. 123-128
Author(s):  
Irina N. Odintsova ◽  
L. F. Pisareva ◽  
O. A. Ananina ◽  
E. V. Panferova

The breast cancer is one of main localizations among malignant tumors in women of the Siberian Federal District. In the structure of morbidity it holds first place with such percentage as 20.4% and index of morbidity makes up to 51.2 per 100 000 of female population. The territories with increased and decreased risk are established. The features of prevalence of disease in a certain degree are conditioned by differences in demographic characteristics of populations. The indices of life-span, birth-rate in fertile age and divorce rate effect the level of morbidity of breast cancer in population.


Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 784 ◽  
Author(s):  
Durga Khandekar ◽  
Venkataswarup Tiriveedhi

Bromodomain and extraterminal domain (BET) proteins have evolved as key multifunctional super-regulators that control gene expression. These proteins have been shown to upregulate transcriptional machinery leading to over expression of genes involved in cell proliferation and carcinogenesis. Based on favorable preclinical evidence of BET inhibitors in various cancer models; currently, 26 clinical trials are underway in various stages of study on various hematological and solid organ cancers. Unfortunately, preliminary evidence for these clinical studies does not support the application of BET inhibitors as monotherapy in cancer treatment. Furthermore, the combinatorial efficiency of BET inhibitors with other chemo-and immunotherapeutic agents remain elusive. In this review, we will provide a concise summary of the molecular basis and preliminary clinical outcomes of BET inhibitors in cancer therapy, with special focus on triple negative breast cancer.


Endocrinology ◽  
1996 ◽  
Vol 137 (8) ◽  
pp. 3368-3374 ◽  
Author(s):  
J Sandstedt ◽  
J Törnell ◽  
E Norjavaara ◽  
O G Isaksson ◽  
C Ohlsson

Author(s):  
Anirban Maitra ◽  
N.V. Rajeshkumar ◽  
Michelle Rudek ◽  
Ignacio Garrido‐Laguna ◽  
Daniel Laheru ◽  
...  

2015 ◽  
Vol 34 (11) ◽  
pp. 1493-1508 ◽  
Author(s):  
Linxiang Lan ◽  
Jane D Holland ◽  
Jingjing Qi ◽  
Stefanie Grosskopf ◽  
Regina Vogel ◽  
...  

2018 ◽  
Vol 19 (7) ◽  
pp. 2116 ◽  
Author(s):  
Agata Pawlik ◽  
Artur Anisiewicz ◽  
Beata Filip-Psurska ◽  
Marcin Nowak ◽  
Eliza Turlej ◽  
...  

In our previous study, calcitriol and its analogs PRI-2191 and PRI-2205 stimulated 4T1 mouse mammary gland cancer metastasis. Therefore, we aimed to analyze the inflammatory response in 4T1-bearing mice treated with these compounds. Gene expression analysis of the splenocytes and regional lymph nodes demonstrated prevalence of the T helper lymphocytes (Th2) response with an increased activity of regulatory T (Treg) lymphocytes in mice treated with these compounds. We also observed an increased number of mature granulocytes and B lymphocytes and a decreased number of TCD4+, TCD4+CD25+, and TCD8+, as well as natural killer (NK) CD335+, cells in the blood of mice treated with calcitriol and its analogs. Among the splenocytes, we observed a significant decrease in NK CD335+ cells and an increase in TCD8+ cells. Calcitriol and its analogs decreased the levels of interleukin (IL)-1β and IL-10 and increased the level of interferon gamma (IFN-γ) in the plasma. In the tumor tissue, they caused an increase in the level of IL-10. Gene expression analysis of lung tissue demonstrated an increased level of osteopontin (Spp1) and transforming growth factor β (TGF-β) mRNA. The expression of Spp1 was also elevated in lymph nodes. Calcitriol and its analogs caused prevalence of tumor-conducive changes in the immune system of 4T1 tumor-bearing mice, despite the induction of some tumor-disadvantageous effects.


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