The Association of Valproic Acid and Incident Breast Cancer in a Managed Care Cohort

2010 ◽  
Author(s):  
Eun-Sil S. Hwang
2021 ◽  
Vol 30 ◽  
pp. 096368972110275
Author(s):  
Zhen Li ◽  
Lina Yang ◽  
Shuai Zhang ◽  
Jiaqi Song ◽  
Huanran Sun ◽  
...  

Energy metabolism programming is a hallmark of cancer, and serves as a potent target of cancer therapy. Valproic acid (VPA), a broad Class I histone deacetylases (HDACs) inhibitor, has been used as a therapeutic agent for cancer. However, the detail mechanism about the potential role of VPA on the Warburg effect in breast cancer remains unclear. In this study, we highlight that VPA significantly attenuates the Warburg effect by decreasing the expression of pyruvate kinase M2 isoform (PKM2), leading to inhibited cell proliferation and reduced colony formation in breast cancer MCF-7 and MDA-MB-231 cells. Mechanistically, Warburg effect suppression triggered by VPA was mediated by inactivation of ERK1/2 phosphorylation through reduced HDAC1 expression, resulting in suppressing breast cancer growth. In summary, we uncover a novel mechanism of VPA in regulating the Warburg effect which is essential for developing the effective approach in breast cancer therapy.


2000 ◽  
Vol 53 (6) ◽  
pp. 605-614 ◽  
Author(s):  
Jean L Freeman ◽  
Dong Zhang ◽  
Daniel H Freeman ◽  
James S Goodwin

Epidemiology ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Humberto Parada ◽  
Tarik Benmarhnia ◽  
Lawrence S. Engel ◽  
Xuezheng Sun ◽  
Chiu-Kit Tse ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mary Branch ◽  
Christopher L Schaich ◽  
Daniel Beavers ◽  
Elsayed Z Soliman ◽  
Kerryn Reding ◽  
...  

Background: Autonomic dysfunction (AD) as measured by heart rate variability (HRV) is associated with increased risk of cardiovascular disease (CVD) and breast cancer. No study has utilized a large prospective multi-center cohort of diverse women to assess differences in HRV associated with incident breast cancer. Objectives: To identify heart rate variability changes in women with breast cancer compared to controls in the Women’s Health Initiative (WHI). Methods: In a retrospective cohort study, we utilized 5,031 women in the WHI CT cohort who were breast cancer free at baseline and compared 1) those with incident breast cancer v. 2) those who were breast cancer free during the ECG follow-up period as controls. HRV was calculated utilizing 10-second ECG with two measures of two-domain HRV: standard deviation of all normal-to-normal RR intervals (SDNN) and the root mean square of successive differences in normal-to-normal RR intervals (rMSSD). HRV was measured from ECGs collected at baseline, years 3, 6, and 9 in the comparison groups. An adjusted mixed linear model was used to evaluate the differences in SDNN and rMSSD comparing women with incident breast cancer to controls. Cardiovascular risk factors utilized in the adjusted model were determined via questionnaire at baseline. Results: At baseline, women with incident breast cancer diagnosed by years 3, 6, or 9 were significantly older (median age 63 vs. 61, P<0.0001) and had a higher prevalence of hypertension (35% vs. 32%, P=0.02). SDNN at years 3 and 6 in women with breast cancer compared to controls was significantly lower (P=0.0002, P=0.03 respectively). As well, rMSSD was significantly lower at year 3 compared to controls (P<0.0001) ( Figure 1 ). Conclusions: HRV as a measure of AD is significantly lower in women with incident breast cancer compared to women without breast cancer. Reduction in HRV is associated with CVD outcomes in the literature. Our study suggests HRV may predict CVD in breast cancer patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zuchao Cai ◽  
David Lim ◽  
Guochao Liu ◽  
Chen Chen ◽  
Liya Jin ◽  
...  

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.


2018 ◽  
Vol 2 (3) ◽  
pp. e021 ◽  
Author(s):  
Paul J. Villeneuve ◽  
Mark S. Goldberg ◽  
Dan L. Crouse ◽  
Teresa To ◽  
Scott A. Weichenthal ◽  
...  

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