Medicine and Health Sciences Commons^™

Design Of Nanoparticle-Based Carriers For Targeted Drug Delivery, Xiaojiao Yu, Ian Trase, Muqing Ren, Kayla Duval, Xing Guo, Zi Chen

Dartmouth Scholarship

Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this paper, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting, and physical targeting) and compare methods of action, advantages, limitations, and the current stages of research. For the most commonly used …

Female Chromosome X Mosaicism Is Age-Related And Preferentially Affects The Inactivated X Chromosome, Mitchell J. Machiela, Weiyin Zhou, Eric Karlins, Joshua N. Sampson, Neal D. Freedman, Qi Yang, Belynda Hicks, Casey Dagnall, Christopher Hautman, Kevin B. Jacobs, Christian C. Abnet, Melinda C. Aldrich, Christopher Amos, Laufey T. Amundadottir, Alan A. Arslan, Laura E. Beane-Freeman, Sonja I. Berndt, Amanda Black, William J. Blot, Cathryn H. Bock, Paige M. Bracci, Louise A. Brinton, H Bas Bueno-De-Mesquita, Laurie Burdett, Julie E. Buring, Mary A. Butler, Federico Canzian, Tania Carreon, Kari G. Chaffee, I-Shou Chang, Nilanjan Chatterjee, Chu Chen, Constance Chen, Kexin Chen, Charles C. Chung, Linda S. Cook, Marta Crous Bou, Michael Cullen, Faith G. Davis, Immaculata De Vivo, Ti Ding, Jennifer Doherty

Dartmouth Scholarship

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events 4 2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses …

Long Non Coding Rna Malat1 Promotes Tumor Growth And Metastasis By Inducing Epithelial-Mesenchymal Transition In Oral Squamous Cell Carcinoma, Xuan Zhou, Su Liu, Guoshuai Cai, Lingping Kong, Tingting Zhang, Yu Ren, Yansheng Wu, Mei Mei, Lun Zhang, Xudong Wang

Dartmouth Scholarship

The prognosis of advanced oral squamous cell carcinoma (OSCC) patients remains dismal, and a better understanding of the underlying mechanisms is critical for identifying effective targets with therapeutic potential to improve the survival of patients with OSCC. This study aims to clarify the clinical and biological significance of metastasis-associated long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OSCC. We found that MALAT1 is overexpressed in OSCC tissues compared to normal oral mucosa by real-time PCR. MALAT1 served as a new prognostic factor in OSCC patients. When knockdown by small interfering RNA (siRNA) in OSCC cell lines TSCCA and …

Dna Methylation In Ductal Carcinoma In Situ Related With Future Development Of Invasive Breast Cancer, Kevin C. Johnson, Devin C. Koestler, Thomas Fleischer, Panpan Chen, Erik G. Jenson, Jonathan D. Marotti, Tracy Onega, Vessela N. Kristenen, Brock C. Christensen

Dartmouth Scholarship

Background: Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-invasive lesion associated with an increased risk for future invasive ductal carcinoma. However, accurate risk stratification for development of invasive disease and appropriate treatment decisions remain clinical challenges. DNA methylation alterations are early events in the progression of cancer and represent emerging molecular markers that may predict invasive recurrence more accurately than traditional measures of DCIS prognosis.

Results: We measured DNA methylation using the Illumina HumanMethylation450K array of estrogen-receptor positive DCIS (n = 40) and adjacent-normal (n = 15) tissues from subjects in the New Hampshire Mammography Network longitudinal breast imaging …

A Novel Caspase 8 Selective Small Molecule Potentiates Trail-Induced Cell Death, Octavian Bucur, Gabriel Gaidos, Achani Yatawara, Bodvael Pennarun, Chamila Rupasinghe, Jérémie Roux, Stefan Andrei, Bingqian Guo, Alexandra Panaitiu, Maria Pellegrini, Dale Mierke, Roya Khosravi-Far

Dartmouth Scholarship

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, …

Integration Of Comprehensive Women’S Health Programmes Into Health Systems: Cervical Cancer Prevention, Care And Control In Rwanda, Agnes Binagwaho, Fidele Ngabo, Claire M. Wagner, Cathy Mugeni, Maurice Gatera, Cameron T. Nutt, Sabin Nsanzimana

Dartmouth Scholarship

PROBLEM: Although it is highly preventable and treatable, cervical cancer is the most common and most deadly cancer among women in Rwanda.

APPROACH: By mobilizing a diverse coalition of partnerships, Rwanda became the first country in Africa to develop and implement a national strategic plan for cervical cancer prevention, screening and treatment.

LOCAL SETTING: Rwanda - a small, landlocked nation in East Africa with a population of 10.4 million - is well positioned to tackle a number of "high-burden" noncommunicable diseases. The country's integrated response to infectious diseases has resulted in steep declines in premature mortality over the past decade. …

Estimating Water Supply Arsenic Levels In The New England Bladder Cancer Study, John R. Nuckols, Laura E. Beane-Freeman, Jay H. Lubin, Matthew S. Airola, Dalsu Baris, Joseph D. Ayotte, Anne Taylor, Chris Paulu, Margaret R. Karagas, Joanne Colt

Dartmouth Scholarship

Background: Ingestion of inorganic arsenic in drinking water is recognized as a cause of bladder cancer when levels are relatively high (≥ 150 µg/L). The epidemiologic evidence is less clear at the low-to-moderate concentrations typically observed in the United States. Accurate retrospective exposure assessment over a long time period is a major challenge in conducting epidemiologic studies of environmental factors and diseases with long latency, such as cancer.

Objective: We estimated arsenic concentrations in the water supplies of 2,611 participants in a population-based case–control study in northern New England.

Methods: Estimates covered the lifetimes of most study participants and were …