An epigenetically distinct breast cancer cell subpopulation promotes collective invasion

Tumor cells can engage in a process called collective invasion, in which cohesive groups of cells invade through interstitial tissue. Here, we identified an epigenetically distinct subpopulation of breast tumor cells that have an enhanced capacity to collectively invade. Analysis of spheroid invasion in an organotypic culture system revealed that these “trailblazer” cells are capable of initiating collective invasion and promote non-trailblazer cell invasion, indicating a commensal relationship among subpopulations within heterogenous tumors. Canonical mesenchymal markers were not sufficient to distinguish trailblazer cells from non-trailblazer cells, suggesting that defining the molecular underpinnings of the trailblazer phenotype could reveal collective invasion-specific mechanisms. Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B, and LPAR1 are highly expressed in trailblazer cells and required to initiate collective invasion, with DOCK10 essential for metastasis. In patients with triple-negative breast cancer, expression of these 7 genes correlated with poor outcome. Together, our results indicate that spontaneous conversion of the epigenetic state in a subpopulation of cells can promote a transition from in situ to invasive growth through induction of a cooperative form of collective invasion and suggest that therapeutic inhibition of trailblazer cell invasion may help prevent metastasis.     

Factors associated with publication of plenary presentations at the Society of Gynecologic Oncologists annual meeting

ObjectiveTo determine the rate and factors associated with publication of plenary abstract presentations from the Society of Gynecologic Oncologists annual meeting.MethodsPlenary presentations were reviewed from 2000 to 2005. A PubMed search was performed to identify subsequent peer-reviewed publication of these presentations. Chi-squared test and logistic regression were used for statistical analyses.ResultsOf 378 main, focused or express plenary presentations, 173 (45.8%) involved multiple and 205 (54.2%) single institutions. The types of study include: chart review (29.4%), cohort study (28.0%), translational (23.5%), and randomized clinical trial (6.9%). 309 (81.7%) of presentations were subsequently published. The median time from presentation to publication was 14 months (range: 1–85). Studies from multiple vs. single institutions were more likely to be published (87.9% vs. 76.6%; p = 0.005). In addition, randomized controlled trials were more likely to be published compared with chart review, cohort, and translation research (92.3% vs. 83.8%, 77.4%, and 74.2%; p < 0.01). On multivariate analysis, multi-institutional studies (OR = 2.28, 95% CI = 1.28–4.04; p = 0.005) and type of study (OR = 1.64, 95% CI = 1.19–2.26; p = 0.002) were independent factors associated with publication. In addition, multi-institutional studies had longer times from presentation to publication compared with their counterparts.ConclusionsA high percentage of plenary presentations at the Society of Gynecologic Oncologists annual meeting resulted in subsequent publication. Multi-institutional studies and randomized clinical trials were more likely to be published.     

A review on nanoparticle-based technologies for biodetoxification

Nanotechnology has gained significant penetration to different fields of medicine including drug delivery, disease interrogation, targeting and bio-imaging. In recent years, efforts have been put forth to assess the use of this technology in biodetoxification. In this review, we will discuss the current status of nanostructured biomaterials/nanoparticle (NP)-based technologies as a candidate biodetoxifying agent. Patient hospitalization due to illicit drug consumption, suicidal attempts and accidental toxin exposure are major challenges in the medical field. Overdoses of drugs/toxic chemicals or exposure to bacterial toxins or poisons are conventionally treated by voiding the stomach, administering activated charcoal or by using specific antidotes, if the toxin is known. Because of the limitations of these methods for safe and effective detoxification, advancements in nanotechnology may offer novel ways in intoxication support by using nanostructured biomaterials, such as liposomes, micellar nanocarriers, liquid crystalline nanoassemblies and ligand-based NPs.     

对产前母体苯巴比妥给药以预防针对新生儿和胎儿溶血病的婴儿换血

胎儿和新生儿溶血病(HDFN)可导致严重的围产期疾病,包括高胆红素血症及其引起的核黄疸。血红素分子解离为胆红素并产生免疫介导的溶血。它与白蛋白结合后转运到肝细胞,再由尿苷二磷酸葡萄糖醛酸转移酶(UGT)酶家族作用而葡萄糖醛酸化。对于人类,这种代谢途径中主要的酶是胆红素-     

Improving HIV Screening and Receipt of Results by Nurse-Initiated Streamlined Counseling and Rapid Testing

Background  HIV testing is cost-effective in unselected general medical populations, yet testing rates among those at risk remain low, even among those with regular primary care. HIV rapid testing is effective in many healthcare settings, but scant research has been done within primary care settings or within the US Department of Veteran’s Affairs Healthcare System. Objectives  We evaluated three methods proven effective in other diseases/settings: nurse standing orders for testing, streamlined counseling, and HIV rapid testing. Design  Randomized, controlled trial with three intervention models: model A (traditional counseling/testing); model B (nurse-initiated screening, traditional counseling/testing); model C (nurse-initiated screening, streamlined counseling/rapid testing). Participants  Two hundred fifty-one patients with primary/urgent care appointments in two VA clinics in the same city (one large urban hospital, one freestanding outpatient clinic in a high HIV prevalence area). Measurements  Rates of HIV testing and receipt of results; sexual risk reduction; HIV knowledge improvement. Results  Testing rates were 40.2% (model A), 84.5% (model B), and 89.3% (model C; p = <.01). Test result receipt rates were 14.6% (model A), 31.0% (model B), 79.8% (model C; all p = <.01). Sexual risk reduction and knowledge improvement did not differ significantly between counseling methods. Conclusions  Streamlined counseling with rapid testing significantly increased testing and receipt rates over current practice without changes in risk behavior or posttest knowledge. Increased testing and receipt of results could lead to earlier disease identification, increased treatment, and reduced morbidity/mortality. Policymakers should consider streamlined counseling/rapid testing when implementing routine HIV testing into primary/urgent care.     

Plasmodium vivax: a cause of malnutrition in young children

We studied the aetiology of malnutrition in a cohort of 1511 children < 10 years old in Espiritu Santo, Vanuatu. Malnutrition was categorized using standard anthropometric criteria as: underweight [weight-for-age (WA) Z score < -2], wasting [weight-for-height (WH) Z < -2], or stunting [height-for-age (HA) Z < -2]. On multiple logistic regression analysis, the only factors significantly associated with wasting were age < 5 years [OR (95% CI) 1.8 (1.2-2.9), p = 0.01] and having suffered one or more episodes of clinical P. vivax malaria in the 6 months preceding nutritional assessment [OR 2.4 (1.3-4.4), p = 0.006]. The incidence of P. vivax infection was significantly higher during the 6 months preceding assessment in underweight vs. non-underweight children [incidence rate ratio (IRR) 2.6 (1.5-4.4), p < or = 0.0001). These groups had similar incidences of clinical P. falciparum infection during the same period [IRR 1.1 (0.57-2.1) p = 0.8] and of either species during the 6 months following assessment [IRR P. vivax 1.3 (0.9- 2.0) p = 0.2; IRR P. falciparum 1.3 (0.9-1.9) p = 0.2]. In these children, P. vivax malaria was a major predictor of acute malnutrition; P. falciparum was not. Wasting neither predisposed to nor protected against malaria of either species. Although P. vivax malaria is generally regarded as benign, it may produce considerable global mortality through malnutrition.