Positive sentinel lymph node in a patient with clinical stage I vaginal cancer.

•Sentinel lymph node mapping is feasible in patients with vaginal cancer.•Here we report a positive sentinel lymph node in a patient with clinically early-stage vaginal cancer.•Sentinel lymph node mapping and dissection may guide primary treatment decisions.

Cellular kinetics of MED12-mutant uterine leiomyoma growth and regression in vivo.

Cellular mechanisms of uterine leiomyoma (LM) formation have been studied primarily utilizing in vitro models. However, recent studies established that the cells growing in the primary cultures of MED12-mutant LM (MED12-LM) do not carry causal mutations. To improve the accuracy of LM research, we addressed the cellular mechanisms of LM growth and regression utilizing a patient-derived xenograft (PDX) model, which faithfully replicates the patient tumors in situ The growth and maintenance of MED12-LMs depend on 17ß-estradiol (E2) and progesterone (P4). We determined E2 and P4-activated MAPK and PI3K pathways in PDXs with upregulation of IGF1 and IGF2, suggesting that the hormone actions on MED12-LM are mediated by the IGF pathway. When hormones were removed, MED12-LM PDXs lost approximately 60% of volume within 3 days through reduction in cell size. However, in contrast to general belief, the survival of LM cells was independent of E2 and/or P4, and apoptosis was not involved in the tumor regression. Furthermore, it was postulated that abnormal collagen fibers promote the growth of LMs. However, collagen fibers of actively growing PDXs were well aligned. The disruption of collagen fibers, as found in human LM specimens, occurred only when the volume of PDXs had grown to over 20 times the volume of unstimulated PDXs, indicating disruption is the result of growth not the cause. Hence, this study revises generally accepted theories on the growth and regression of LMs.

To Assess the Success of Computerized Order Sets and Pharmacy Education Modules in Improving Antiretroviral Prescribing.

PURPOSE: To assess the success of order set and pharmacist training improvement (OSPTI) in improving prescription of antiretroviral therapy (ART) in a tertiary care, public, teaching hospital. METHODS: In this pre-OSPTI (January 2012 through June 2013) and post-OSPTI study (July 2013 through September 2014), an infectious disease pharmacist reviewed all patients on ART. A review of intervention data in July 2013 led to order-set changes in the hospital's computerized order entry system for frequently intervened on antiretrovirals: ritonavir, tenofovir, emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), and lamivudine. Concurrently, case-based education modules were conducted to help pharmacists identify ART errors. The number of patients on ART, number of interventions, and types of ritonavir interventions were compared between pre- and post-OSPTI periods. RESULTS: In the pre-OSPTI period, an average of 239 patients were reviewed per quarter compared to an average of 216 per quarter in the post-OSPTI period. After implementing enhanced order sets, the number of interventions decreased by approximately 34% ( P < .0001). The number of ritonavir interventions decreased on average by 45% ( P < .0001), although the types of ritonavir interventions were similar. CONCLUSION: Enhanced antiretroviral order sets and pharmacy education modules improved ART prescription by reducing the overall number of antiretroviral interventions required per quarter. This modality was effective in improving prescribing of ART and reducing the need for pharmacist interventions.

Subtype-Specific Tumor-Associated Fibroblasts Contribute to the Pathogenesis of Uterine Leiomyoma.

Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with distinctive genetic alterations. Here, we report the elucidation of the biological characteristics of the two most prevalent uterine leiomyoma subtypes, MED12-mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) uterine leiomyomas. Because each tumor carries only one genetic alteration, both subtypes are considered to be monoclonal. Approximately 90% of cells in HMGA2-uterine leiomyoma were smooth muscle cells (SMC) with HMGA2 overexpression. In contrast, MED12-LM consisted of similar numbers of SMC and non-SMC, which were mostly tumor-associated fibroblasts (TAF). Paradoxically, TAF carried no mutations in MED12, suggesting an interaction between SMC and TAF to coordinate their growth. The higher amount of extracellular matrix in MED12-LM than HMGA2-LM was partially due to the high concentration of collagen-producing TAF. SMC growth in a xenograft assay was driven by progesterone in both uterine leiomyoma subtypes. In contrast, TAF in MED12-LM proliferated in response to estradiol, whereas progesterone had no effect. The high concentration of estrogen-responsive TAF in MED12-LM explains the inconsistent discoveries between in vivo and in vitro studies on the mitogenic effect of estrogen and raises questions regarding the accuracy of previous studies utilizing MED12-LM cell culture. In addition, the differential effects of estradiol and progesterone on these uterine leiomyoma subtypes emphasize the importance of subtypes and genotypes in designing nonsurgical therapeutic strategies for uterine leiomyoma. Cancer Res; 77(24); 6891-901. ©2017 AACR.

Use of ß-blockers and mortality following ovarian cancer diagnosis: a population-based cohort study.

BACKGROUND: Experimental data suggest that catecholamine hormones are involved in stimulating the aggressiveness of ovarian cancer, but few population-based studies have examined this association. We therefore conducted a population-based cohort study to examine whether ß-blockers affect mortality following ovarian cancer diagnosis. METHODS: We used the Danish Cancer Registry to identify all patients diagnosed with ovarian cancer in northern Denmark between 1999 and 2010 (n=6,626). Data on medication use, comorbidity, and survival were obtained from medical databases. According to the last redeemed prescription before diagnosis, ß-blocker use was categorized as current (within ≤90 days), previous (>90 days) or never. We used Cox proportional hazards regression to calculate hazard ratios (HRs) for all-cause mortality with 95% confidence intervals (CIs) adjusting for confounding factors. RESULTS: Among the ovarian cancer patients, 373 (5.6%) were current, 87 (1.3%) previous, and 6,166 (93.1%) were nonusers of ß-blockers. Median duration of use was 19.0 months among current users and 43.0 months among previous users. Median follow-up was 2.55 years (IQR: 0.81-9.23). Nonusers and current users of ß-blockers had similar comorbidity burden whereas previous users had moderate comorbidity more frequently. Compared with nonusers, the adjusted HR was 1.17 (95% CI: 1.02-1.34) for current users and 1.18 (95% CI: 0.90-1.55) for previous users. Secondary analyses stratifying by cancer stage and duration of ß-blocker use supported the overall results. CONCLUSIONS: We found no evidence that ß-blocker use was associated with decreased mortality following ovarian cancer diagnosis.

Image states at the interface with a dipolar organic semiconductor.

Image states of the dipolar organic semiconductor vanadyl naphthalocyanine on highly oriented pyrolytic graphite are investigated in the submonolayer to few monolayer regime. The presence of a significant molecular dipole in the organized thin films leads to a strong modification of the image states with coverage. In the 0-1 ML regime, we observe successive stabilization of the image state with increasing coverage. Above 1 ML, a new image state develops, corresponding to the screened interaction at the organic semiconductor/substrate interface. We show that the evolution of the observed image states can be understood on the basis of resonance-enhanced anion formation in the presence of strong electric fields. These data represent a step toward understanding the influence of electrostatic fields on electronic structure at organic semiconductor interfaces.

Confocal single molecule fluorescence spectroscopy in ultrahigh vacuum.

We have constructed an ultrahigh vacuum confocal fluorescence microscope with the purpose of performing single molecule spectroscopy under highly defined conditions. The microscope is designed for high stability while affording the capability of sample preparation, sample transfer, and optical detection in ultrahigh vacuum. It achieves near-diffraction-limited performance and allows the observation of single molecule fluorescence dynamics over extended periods of time. The design of the microscope is discussed in detail and the performance is demonstrated with single molecule fluorescence images and trajectories of N,N'-dibutylperylene-3,4,9,10-dicarboxyimide deposited onto several different surfaces. This instrument further enhances the array of available surface science techniques, permitting spectroscopic investigations of molecule-surface interactions at the single molecule level and on insulating surfaces.

Single molecule power-law behavior on a crystalline surface.

Single perylene bisimide molecules deposited onto Al(2)O(3) (0001) and investigated under controlled ultrahigh vacuum conditions display fluorescence intermittency behavior characteristic of an interfacial charge transfer process. Remarkably, even though the molecules are deposited on a crystalline surface with reduced disorder, power-law-distributed bright and dark periods are observed. These data can be understood based on activated formation of localized small polaron states in Al(2)O(3) (0001). We present a kinetic scheme capable of explaining the occurrence of power-law distributions for both "on" and "off" periods for single molecules on the sapphire substrate. These findings represent a first step toward understanding interfacial charge transfer processes under controlled conditions on crystalline surfaces and at the single molecule level.