Management of patients with diabetes who are receiving insulin may be optimized by clinical pharmacy specialist use of the CCHT program. Although no statistically significant difference was demonstrated with respect to change in A1C from baseline to 6 months, the CCHT group did show significantly greater differences than the non-CCHT group in A1C at 3 and 6 months, coupled with higher achievement of ADA A1C goals after 6 months.

Cells composing the mammary secretory compartment have evolved a high capacity to secrete not only proteins but also triglycerides and carbohydrates. This feature is illustrated by the mouse, which can secrete nearly twice its own weight in milk proteins, triglycerides and lactose over a short 20-day lactation. The coordination of synthesis and export of products in other secretory cells is orchestrated in part by the transcription factor X-box binding protein 1 (XBP1). To assess the role of XBP1 in mammary epithelial cells (MEC), we studied floxed XBP1 female mice lacking (wild type; WT) or expressing the Cre recombinase under the control of the ovine β-lactoglobulin promoter (ΔXBP1(MEC)). Pregnant ΔXBP1(MEC) females had morphologically normal mammary development and gave birth to the same number of pups as WT mice. Their litters, however, suffered a weight gain deficit by lactation day 3 (L3)3 that grew to 80% by L14. ΔXBP1(MEC) dams had only modest changes in milk composition (-21% protein, +24% triglyceride) and in the expression of associated genes in isolated MEC. By L5, WT glands were fully occupied by dilated alveoli, whereas ΔXBP1(MEC) glands contained fewer, mostly unfilled alveoli and retained a prominent adipocyte population. The smaller epithelial compartment in ΔXBP1(MEC) glands was explained by lower MEC proliferation and increased apoptosis. Finally, endoplasmic reticulum ribbons were less abundant in ΔXBP1(MEC) at pregnancy day 18 and failed to increase in abundance by L5. Collectively, these results show that XBP1 is required for MEC population expansion during lactation and its ability to develop an elaborate endoplasmic reticulum compartment.

Female mammals call on hormonally driven metabolic adaptations to meet the energy demand of late pregnancy and lactation. These maternal adaptations preserve limiting nutrients and promote their transfer to the uterus during pregnancy or mammary gland during lactation. The novel metabolic hormone fibroblast growth factor-21 (FGF21) was recently shown to increase suddenly at the onset of lactation in dairy cows, but whether FGF21 is induced during the reproductive cycle of other mammals is unknown. To start addressing this question, we studied subsets of mice when virgin (V), on day 18 of pregnancy (P18) and on lactation day 1 (L1), L5 and L14. Plasma FGF21 increased from nearly undetectable levels to over 8 ng/ml between V and P18 and returned to V levels by L1. Gene expression studies showed that liver was the major source of plasma FGF21 at P18 with little or no contribution from other known expressing tissues or from the developing placenta and mammary epithelial cells. The increased FGF21 production at P18 was dissociated from plasma nonesterified fatty acids and liver lipids, unlike that seen in fasted V mice. Changes in FGF21 signaling components in target tissues were modest except for reduced β-Klotho and FGFR1c expression in P18 adipose tissue. The placenta expressed both β-Klotho and FGFR1c, raising the possibility that it responds to FGF21. In conclusion, maternal FGF21 is increased when products of conception account for ∼ 40% of maternal weight, suggesting that FGF21 orchestrates some of the adaptations needed to meet the energy demand of late pregnancy.

Early patient identification and education on treatment rationale, delivery, and expectations help ensure a successful sipuleucel-T treatment experience. A multidisciplinary coordinated-care process can facilitate proficient sipuleucel-T delivery, and the selection of a primary contact for care coordination offers benefits, such as clear and efficient education.

35 Background: In men with high grade PC and rapid PSA progression after RP, failure rates are unacceptably high despite salvage RT. Androgen deprivation therapy (ADT) is not curative in this setting and we thus evaluated a novel multi-modality approach of systemic chemotherapy and anti-angiogenic therapy prior to prostate bed salvage RT in a multicenter trial. Methods: Eligible men had a rising PSA of 0.1-3.0 ng/ml within 4 years of RP, no metastatic disease except resected positive nodes, no prior ADT, and Gleason 7-10. Men received 4 cycles of docetaxel 70 mg/m2 q3w with prednisone 5 mg bid and sunitinib 37.5 mg qd for 14/21 days each cycle. Salvage RT (66Gy/33fx) to the prostate bed started at day 100. The primary endpoint was progression-free survival at 2 years (PFS2), defined as a confirmed PSA rise above the post-RT nadir or baseline if no nadir occurred, clinical/radiographic progression, or death from date of enrollment. Safety and dose-limiting toxicities were evaluated. This was a single arm prospective open-label phase 2 trial. Results: Thirty-four men accrued in this multisite Dept. of Defense Prostate Cancer Clinical Trials Consortium trial (median age 62, 85% Caucasian, 9% African American); 24% were node positive at surgery, 47% had Gleason 8-10. Median PSA at entry was 0.54 (range 0.2-2.8) and median time since RP was 11 months. The trial was terminated prematurely due to excess dose-limiting toxicity (9 DLT events) including grade 3 events of hand-foot syndrome (n=4), neutropenic fever (n=2), AST increase (n=1), fatigue (n=1), and vomiting with diarrhea (n=1). PFS at 2 years was 48.9% (95% CI: 32.8%, 67.2%) with a median PFS of 26.2 mo (95% CI: 12.5, -). Six men (17.6%) had an undetectable PSA at 2 years. Conclusions: Sunitinib and docetaxel/prednisone followed by salvage RT resulted in excess pre-specified DLTs. However, efficacy data suggests that some men achieved durable long-term disease control with this aggressive approach. Longer-term follow-up and comparative data with salvage XRT and ADT is needed to fully understand the risks/benefits of this combined modality approach in high risk PSA-recurrent PC. Clinical trial information: NCT00734851.