Speaking vocabulary of first grade children

Thesis (Ed.M.)--Boston Universit

Triazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors

Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with Hsp90 N-terminal inhibitors under clinical investigation. Based upon prior SAR trends, a 1,2,3-triazole side chain was placed in lieu of the aryl side chain and attached to both the coumarin and biphenyl scaffold. Antiproliferative studies against SKBr3 and MCF-7 breast cancer cell lines demonstrated these triazole-containing compounds to exhibit improved activity. These compounds were shown to manifest Hsp90 inhibitory activity through Western blot analysis and represent a new scaffold upon which more potent inhibitors can be pursued

Antigen-Specific B Memory Cell Responses to Plasmodium falciparum Malaria Antigens and Schistosoma haematobium Antigens in Co-Infected Malian Children

Polyparasitism is common in the developing world. We have previously demonstrated that schistosomiasis-positive (SP) Malian children have age-dependent protection from malaria compared to matched schistosomiasis-negative (SN) children. Evidence of durable immunologic memory to malaria antigens is conflicting, particularly in young children and the effect of concomitant schistomiasis upon acquisition of memory is unknown. We examined antigen-specific B memory cell (MBC) frequencies (expressed as percentage of total number of IgG-secreting cells) in 84 Malian children aged 4–14 to malaria blood-stage antigens, apical membrane antigen 1 (AMA-1) and merozoite surface protein 1 (MSP-1) and to schistosomal antigens, Soluble Worm Antigenic Preparation (SWAP) and Schistosoma Egg Antigen (SEA), at a time point during the malaria transmission season and a follow-up dry season visit. We demonstrate, for the first time, MBC responses to S. haematobium antigens in Malian children with urinary egg excretion and provide evidence of seasonal acquisition of immunologic memory, age-associated differences in MBC acquisition, and correlation with circulating S. haematobium antibody. Moreover, the presence of a parasitic co-infection resulted in older children, aged 9–14 years, with underlying S. haematobium infection having significantly more MBC response to malaria antigens (AMA1 and MSP1) than their age-matched SN counterparts. We conclude that detectable MBC response can be measured against both malaria and schistosomal antigens and that the presence of S. haematobium may be associated with enhanced MBC induction in an age-specific manner

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Digital CSU Meeting

Ann Marie and Justin will provide an overview of digital production tools, tech-enhanced learning spaces, and other resources offered by the Michael Schwartz Library to support digital/multimodal assignment development. This Digital CSU session is for all faculty, staff, or students who Already assign or have completed multimodal projects Want to know more about what multimodal composing is Want to know what resources MSL has to support multimodal project design Want to understand how multimodal projects can enhance student learning Light refreshments will be served

Impact of Health-related Quality of Life and Prediagnosis Risk of Major Depressive Disorder on Treatment Choice in Low- and Intermediate-Risk Prostate Cancer

BackgroundTreatment for low-risk (LR), favorable intermediate-risk (FIR), and unfavorable intermediate-risk (UIR) prostate cancer (PC) is complicated by clinical equipoise between multiple options. It is unknown how prediagnosis health-related quality of life (HRQoL) and major depressive disorder (MDD) risk impact treatment decisions.ObjectiveTo analyze associations of patient-reported HRQoL and MDD risk with treatment for LR, FIR, and UIR PC patients.Design setting and participantsUsing the Surveillance, Epidemiology and End Results and Medicare Health Outcomes Survey-linked database, we identified 1678 PC patients (498 with LR, 685 with FIR, and 495 with UIR) aged ≥65 yr and diagnosed between 2004 and 2015, who completed the health outcomes survey ≤24 mo before diagnosis.Outcome measurements and statistical analysisHRQoL was measured by physical (PCS) and mental (MCS) component summaries of the Medical Outcomes Study Short Form 36 (SF-36) and Veterans RAND 12-item (VR-12) health survey instruments. MDD risk was derived from survey items screening for depressive symptoms. Associations with treatment choice were assessed by multivariable multinomial logistic regression.Results and limitationsLR patients with higher PCS scores were more likely to receive radiation than surgery (adjusted odds ratio [AOR] 1.5 [95% confidence interval {CI}: 1.1-2.1; p = 0.02]). FIR patients with MDD risk were more likely to receive neither treatment than surgery or radiation (surgery: AOR 2.6 [95% CI: 1.1-6.2; p = 0.03]; radiation: AOR 2.2 [95% CI: 1.2-4.2; p = 0.01]). UIR patients with MDD risk were more likely to undergo radiation than surgery (AOR 2.3 [95% CI: 1.0-4.9; p =0.04]). Additionally, higher PCS scores were associated with receipt of surgery compared with neither treatment (AOR 1.5 [95% CI: 1.1-2.0; p =0.01]). This study is limited by its retrospective design.ConclusionsOlder PC patients with MDD risk received less invasive treatments in the FIR and UIR groups. Higher PCS scores were associated with treatment modality in LR and UIR patients. HRQoL and MDD risk impact treatment choice, warranting additional study.Patient summaryTreatment of prostate cancer requires thoughtful decision-making processes. This study shows that both pretreatment mental status and pretreatment physical status affect treatment decisions, and should be considered during counseling