Small-bubble transport and splitting dynamics in a symmetric bifurcation.

Simulations of small bubbles traveling through symmetric bifurcations are conducted to garner information pertinent to gas embolotherapy, a potential cancer treatment. Gas embolotherapy procedures use intra-arterial bubbles to occlude tumor blood supply. As bubbles pass through bifurcations in the blood stream nonhomogeneous splitting and undesirable bioeffects may occur. To aid development of gas embolotherapy techniques, a volume of fluid method is used to model the splitting process of gas bubbles passing through artery and arteriole bifurcations. The model reproduces the variety of splitting behaviors observed experimentally, including the bubble reversal phenomenon. Splitting homogeneity and maximum shear stress along the vessel walls is predicted over a variety of physical parameters. Small bubbles, having initial length less than twice the vessel diameter, were found unlikely to split in the presence of gravitational asymmetry. Maximum shear stresses were found to decrease exponentially with increasing Reynolds number. Vortex-induced shearing near the bifurcation is identified as a possible mechanism for endothelial cell damage.

Preoperative predictors of delay in initiation of adjuvant chemotherapy in patients undergoing primary debulking surgery for ovarian cancer.

OBJECTIVE: The objective of this study was to identify preoperative characteristics of patients that experience a delay in initiation of adjuvant chemotherapy after primary debulking surgery for ovarian cancer. MATERIALS/METHODS: We performed a retrospective review of patients with Stage II to IV high-grade epithelial ovarian, tubal, and peritoneal carcinoma who underwent primary debulking surgery followed by adjuvant chemotherapy from 2005 to 2013. Patients were divided into 2 groups: Control (those who received their first cycle of chemotherapy within 6weeks of debulking surgery) vs. chemotherapy delay (those who received their first cycle of chemotherapy at an interval >6weeks from primary debulking surgery). Relevant clinical variables and survival outcomes were compared between the 2 groups using standard statistical methods. RESULTS: A total of 221 patients were included in the analyses - 169 (76.5%) were in the control group and 52 (23.5%) were in the chemo delay group. On multi-variate analysis, risk factors that were significantly associated with a delay in initiation in chemotherapy included: age >65, albumin <3.5, and high age-adjusted Charlson Comorbidity Index score. Delay in chemotherapy initiation was associated with a shorter progression-free (p=0.014) but not overall survival (p=0.19). CONCLUSIONS: Delay in initiation of chemotherapy affected 23.5% of patients in our study population. Easily identifiable risk factors for chemotherapy delay exist that can help us pre-operatively identify patients for which neoadjuvant chemotherapy may be a better treatment option. Further study into prospective modeling with these identified risk factors is warranted.

Dietary energy restriction, in part through glucocorticoid hormones, mediates the impact of 12-O-tetradecanoylphorbol-13-acetate on jun D and fra-1 in Sencar mouse epidermis.

Dietary energy restriction (DER, 40% calorie reduction from fat and carbohydrate) inhibited mouse skin carcinogenesis and decreased 12-O-tetradecanoyl-13-phorbol acetate (TPA)-induced activator protein-1 (AP-1):DNA binding previously. This study measured protein levels of c-jun, jun B, jun D, c-fos, fra-1, and fra-2 and examined their contribution to AP-1:DNA binding by electrophoretic mobility shift assay (EMSA) with supershift analysis in the epidermis of control and DER Sencar mice exposed to TPA. TPA significantly increased c-jun, jun B, c-fos, fra-1, and fra-2 and decreased jun D within 3-6 h after treatment. AP-1:DNA binding reached a maximum 2.5-fold induction over controls 4 h after TPA treatment and antibodies to jun B, jun D, and fra-2 in the EMSA binding reaction resulted in supershifts in both acetone- and TPA-treated mice 1-6 h after treatment. The effect of corticosterone (CCS) and DER on the AP-1 proteins and on the composition of the AP-1:DNA complex was measured in adrenalectomized (adx) mice. DER reduced the TPA impact on jun D and enhanced the induction of fra-1. In addition, CCS-supplemented groups had significantly lower jun D and higher fra-2 than adx groups and sham groups. While sham animals treated with either acetone or TPA contained jun B, jun D, and fra-2 proteins in the AP-1:DNA complex by supershift analysis, fra-2 was no longer seen in adx DER animals. In summary, our study supports potential roles for jun D, jun B, and fra-1 in the DER regulation of AP-1 function in the Sencar mouse skin carcinogenesis model.