Anti-galectin-3 peptides increase apoptosis in galectin-3 expressing human breast cancer cells

Abstract only availableA critical factor in the proliferation and the metastatic nature of carcinoma cells appears to be their resistance to natural programmed cell death (apoptosis). However, the molecular mechanisms that enable carcinoma cells to become resistant to cell death are unclear. Galectin-3 (Gal-3) is a protein that is found at elevated levels in a variety of primary and metastatic tumor cells that may play a key role in chemo-resistance and proliferation of carcinoma cells. Gal-3 has also been found to play a key role in the regulation of common apoptosis commitment pathways. Therefore, we hypothesize that peptides, which bind to and inhibit Gal-3 functions, could be used to reduce the anti-apoptotic activity of Gal-3 thus increasing the occurrence of cell death in carcinoma cells. Two cell lines were cultured, the human breast cancer cell line BT549 and a Gal-3-transfected derivative of BT549 (BT549/V). After undergoing apoptosis induction with 0.5 M staurosporine, apoptosis markers were detected fluorescently using flow cytometry. Our preliminary data suggests that, in the absence of anti-galectin-3 peptides, the parent BT549 cell line exhibits mitochondrial damage (decrease in mitochondrial membrane potential as detected by using MitoTracker Red fluorescence) by 6 hours of staurosporine treatment, whereas the BT549/V cell line shows little change in MitoTracker Red fluorescence even after 8 hours of apoptosis induction. A similar pattern is observed when changes in MitoTracker Red fluorescence are correlated with changes in phosphatidylserine translocation from the inner to outer surface of the plasma membrane. The current data suggest that cells transfected with Gal-3 have an increased rate of survival after apoptosis induction. In the next phase of this ongoing project, flow cytometric studies of changes in membrane permeability and DNA damage in parent and galectin-3 transfected BT549 cells will be conducted to further define the time-dependent apoptotic response of the BT549 parent versus BT549/V cells. Finally, we will observe and compare the effect of anti-Gal-3 peptides on induction of apoptosis in these two cell lines in order to determine if Gal-3 plays a key role in the anti-apoptotic nature of carcinoma cells and to test if anti-Gal-3 peptides are efficacious in inhibiting the anti-apoptotic functions of Gal-3.Molecular Imaging Progra

Low Temperature Liquid Metal Batteries for Energy Storage Applications

The present invention relates to a molten metal battery of liquid bismuth and liquid tin electrodes and a eutectic electrolyte. The electrodes may be coaxial and coplanar. The eutectic electrolyte may be in contact with a surface of each electrode. The eutectic electrolyte may comprise ZnC12:KCI

Assessing the effectiveness and cost effectiveness of adaptive e-Learning to improve dietary behaviour: systematic review protocol

Research tools produced to support a systematic review of literature on the use of adaptive e-Learning to improve dietary behaviours

Exploring the Role of Leadership in Facilitating Change to Improve Cancer Survival: An Analysis of Experiences in Seven High Income Countries in the International Cancer Benchmarking Partnership (ICBP).

BACKGROUND: The differences in cancer survival across countries and over time are well recognised, with progress varying even among high-income countries with comparable health systems. Previous research has examined several possible explanations, but the role of leadership in systems providing cancer care has attracted little attention. As part of the International Cancer Benchmarking Partnership (ICBP), this study looked at diverse aspects of leadership to identify drivers of change and opportunities for improvement across seven high-income countries. METHODS: Key informants in 13 jurisdictions were interviewed: Australia (2 states), Canada (3 provinces), Denmark, Ireland, New Zealand, Norway and United Kingdom (4 countries). Participants represented a range of stakeholders at different tiers of the system. They were recruited through a combination of purposive and 'snowball' strategies and participated in semi-structured telephone interviews. Interview transcripts were analysed thematically drawing on the World Health Organization (WHO) health systems framework and previous work analysing national cancer control programmes (NCCPs). RESULTS: Several facets of leadership were perceived as important for improving outcomes. These included political leadership to initiate and maintain progress, intellectual leadership to support those engaged in local implementation of national policies and drive change, and a coherent vision from leaders at different levels of the system. Clinical leadership was also viewed as vital for translating policy into action. CONCLUSION: Certain aspects of cancer care leadership emerged as underpinning and sustaining improvements, such as appointing a central agency, involving clinicians at every stage, ensuring strong leadership of cancer care with a consistent political mandate. Improving cancer outcomes is challenging and complex, but it is unlikely to be achieved without effective leadership, both political and clinical

Investigating the Heart of a Community: Archaeological Excavations at the African Meeting House, Boston, Massachusetts

In collaboration with the Museum of African American History, an archaeological research team from the University of Massachusetts Boston carried out a data recovery excavation at the African Meeting House on Beacon Hill. The African Meeting House was a powerful social institution for 19thcentury Boston’s free black community. The site played an important role in the abolition movement, the creation of educational opportunity, and other community action for social and political equality. The Meeting House was originally built in 1806, and renovations in preparation for the 2006 bi-centennial celebration prompted an investigation of areas of the property to be impacted by the proposed construction. Archaeological fieldwork, conducted under Massachusetts Historical Commission Permit Number 2750, was spread over seven weeks in May through July 2005. The field team opened and explored about 19 m2 of the site in the backlot south of the Meeting House and alley to the west. These excavations recorded information about a series of significant features and deposits, and collected over 38,000 artifacts and a series of soil samples for a detailed archaeobiological research program. These excavations met the requirements of the data recovery program as outlined in 950 CMR 70.00 and in the Memorandum of Agreement for the project, and the proposed renovation work proceeded with a finding of no adverse effect (36 CFR 800.5(b)). The depositional history and the nature of the archaeological record allow us to separate the overall excavation into three sub-areas: 1) the west alley between the AMH and 2 Smith Court; 2) the historic Meeting House backlot; and 3) the south yard, which originally belonged to the 44 Joy Street property. In terms of significant features and deposits, the west alley was almost entirely a series of builders’ trenches reflecting the historic sequence of construction and remodeling of the Meeting House and adjacent buildings to the west. In the backlot, the units against the south wall of the Meeting House contained similar builders’ trenches. The backlot also contained a series of stone and brick drains and a trash-rich midden layer. The vast majority of artifacts in the Meeting House backlot date from about 1806–1840. The ceramics assemblage is particularly large, and reflects both community meals at the Meeting House and business of Domingo Williams, a caterer who rented a basement apartment. Finally, only one feature was studied in the south yard, a privy (outhouse) that was for the 44 Joy Street property. The bottommost layer of the privy was an artifact rich nightsoil layer, dating to about 1811–1838, and containing the trash of African American tenants living at 44 Joy Street. Together, the archaeological deposits in the backlot provide a variety of insights into living conditions, economic opportunity, foodways, health, and daily life for 19th-century Boston’s free black community. These results thus provide information to help further the research, interpretation, and public education goals of the Museum of African American History

Risk of Uterine Rupture and Placenta Accreta With Prior Uterine Surgery Outside of the Lower Segment

Objective—Women with a prior myomectomy or prior classical cesarean delivery are often delivered early by cesarean due to concern for uterine rupture. Although theoretically at increased risk for placenta accreta, this risk has not been well quantified. Our objective was to estimate and compare the risks of uterine rupture and placenta accreta in women with prior uterine surgery. Methods—Women with prior myomectomy or prior classical cesarean delivery were compared to women with a prior low transverse cesarean to estimate rates of both uterine rupture and placenta accreta. Results—One hundred seventy-six women with a prior myomectomy, 455 with a prior classical cesarean delivery, and 13,273 women with a prior low transverse cesarean were evaluated. Mean gestational age at delivery differed by group (p0.99) or in the prior classical cesarean delivery group (0.88%, p=0.13). Placenta accreta occurred in 0% (95% CI 0-1.98%) of prior myomectomy compared with 0.19% in the low transverse cesarean group (p>0.99) and 0.88% in the prior classical cesarean delivery group (p=0.01 relative to low transverse cesarean). The adjusted OR for the prior classical cesarean delivery group (relative to low transverse cesarean) was 3.23 (1.11-9.39) for uterine rupture and 2.09 (0.69-6.33) for accreta. The frequency of accreta for those with previa was 11.1% for the prior classical cesarean delivery and 13.6% for low transverse cesarean groups (p>0.99=1.0). Conclusion—A prior myomectomy is not associated with higher risks of either uterine rupture or placenta accreta. The absolute risks of uterine rupture and accreta after prior myomectomy are low

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes

Use of Carpenter-Coustan compared to National Diabetes Data Group (NDDG) criteria increases the number of women diagnosed with GDM by 30-50%, but whether treatment of this milder GDM reduces adverse outcomes is unknown. We explored the effects of the diagnostic criteria used on the benefits of GDM treatment

Quality of Care for HIV Infection Provided by Ryan White Program-Supported versus Non-Ryan White Program-Supported Facilities

BACKGROUND: The Ryan White HIV/AIDS Care Act (now the Treatment Modernization Act; Ryan White Program, or RWP) is a source of federal public funding for HIV care in the United States. The Health Services and Resources Administration requires that facilities or providers who receive RWP funds ensure that HIV health services are accessible and delivered according to established HIV-related treatment guidelines. We used data from population-based samples of persons in care for HIV infection in three states to compare the quality of HIV care in facilities supported by the RWP, with facilities not supported by the RWP. METHODOLOGY/PRINCIPAL FINDINGS: Within each area (King County in Washington State; southern Louisiana; and Michigan), a probability sample of patients receiving care for HIV infection in 1998 was drawn. Based on medical records abstraction, information was collected on prescription of antiretroviral therapy according to treatment recommendations, prescription of prophylactic therapy, and provision of recommended vaccinations and screening tests. We calculated population-level estimates of the extent to which HIV care was provided according to then-current treatment guidelines in RWP-supported and non-RWP-supported facilities. For all treatment outcomes analyzed, the compliance with care guidelines was at least as good for patients who received care at RWP-supported (vs non-RWP supported) facilities. For some outcomes in some states, delivery of recommended care was significantly more common for patients receiving care in RWP-supported facilities: for example, in Louisiana, patients receiving care in RWP-supported facilities were more likely to receive indicated prophylaxis for Pneumocystis jirovecii pneumonia and Mycobacterium avium complex, and in all three states, women receiving care in RWP-supported facilities were more likely to have received an annual Pap smear. CONCLUSIONS/SIGNIFICANCE: The quality of HIV care provided in 1998 to patients in RWP-supported facilities was of equivalent or better quality than in non-RWP supported facilities; however, there were significant opportunities for improvement in all facility types. Data from population-based clinical outcomes surveillance data can be used as part of a broader strategy to evaluate the quality of publicly-supported HIV care