Medicine and Health Sciences Commons^™

The Current State Of Molecular Testing In The Treatment Of Patients With Solid Tumors, 2019., Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall

Articles, Abstracts, and Reports

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up-to-date sources to ensure he or …

An Inflammatory Landscape For Preoperative Neurologic Deficits In Glioblastoma., Amal Katrib, Hyun-Hwan Jeong, Nina L Fransen, Kristin S Henzel, Jeremy A Miller

Articles, Abstracts, and Reports

No abstract provided.

Implantable Biomaterials To Provide Local Immunotherapy Following Surgical Resection., Michael J Gough, Jason R Baird, R Bryan Bell

Articles, Abstracts, and Reports

No abstract provided.

Unleashing Endogenous Tnf-Alpha As A Cancer Immunotherapeutic., Steven F Josephs, Thomas E Ichim, Stephen M Prince, Santosh Kesari, Francesco M Marincola, Anton Rolando Escobedo, Amir Jafri

Articles, Abstracts, and Reports

Tumor necrosis factor (TNF)-alpha was originally identified in the 1970s as the serum mediator of innate immunity capable of inducing hemorrhagic necrosis in tumors. Today, a wide spectrum of biological activities have been attributed to this molecule, and clinical translation has mainly occurred not in using it to treat cancer, but rather to inhibit its effects to treat autoimmunity. Clinical trials utilizing systemic TNF-alpha administration have resulted in an unacceptable level of toxicities, which blocked its development. In contrast, localized administration of TNF-alpha in the form of isolated limb perfusion have yielded excellent results in soft tissue sarcomas. Here we …

Protection From Chemotherapy- And Antibiotic-Mediated Dysbiosis Of The Gut Microbiota By A Probiotic With Digestive Enzymes Supplement., Thomas E Ichim, Santosh Kesari, Kim Shafer

Articles, Abstracts, and Reports

There are numerous downstream consequences of marketed drugs like antineoplastic agents on the gut microbiome, an effect that is suggested to contribute to adverse event profiles and may also influence drug responses. In cancer, progress is needed toward modulation of the host microbiome to prevent off-target side effects of drugs such as gastrointestinal mucositis that result from gut dysbiosis. The objective of this study was evaluation of the bioactivity of a supplement consisting of capsules with a blend of 9 probiotic organisms of the genera

Recurrent Tumor-Specific Regulation Of Alternative Polyadenylation Of Cancer-Related Genes., Zhuyi Xue, René L Warren, Ewan A Gibb, Daniel Macmillan, Johnathan Wong, Readman Chiu, S Austin Hammond, Chen Yang, Ka Ming Nip, Catherine A Ennis, Abigail Hahn, Sheila Reynolds, Inanc Birol

Articles, Abstracts, and Reports

BACKGROUND: Alternative polyadenylation (APA) results in messenger RNA molecules with different 3' untranslated regions (3' UTRs), affecting the molecules' stability, localization, and translation. APA is pervasive and implicated in cancer. Earlier reports on APA focused on 3' UTR length modifications and commonly characterized APA events as 3' UTR shortening or lengthening. However, such characterization oversimplifies the processing of 3' ends of transcripts and fails to adequately describe the various scenarios we observe.

RESULTS: We built a cloud-based targeted de novo transcript assembly and analysis pipeline that incorporates our previously developed cleavage site prediction tool, KLEAT. We applied this pipeline to …

Digitizing Omics Profiles By Divergence From A Baseline., Wikum Dinalankara, Qian Ke, Yiran Xu, Lanlan Ji, Nicole Pagane, Anching Lien, Tejasvi Matam, Elana J Fertig, Nathan D Price, Laurent Younes, Luigi Marchionni, Donald Geman

Articles, Abstracts, and Reports

Data collected from omics technologies have revealed pervasive heterogeneity and stochasticity of molecular states within and between phenotypes. A prominent example of such heterogeneity occurs between genome-wide mRNA, microRNA, and methylation profiles from one individual tumor to another, even within a cancer subtype. However, current methods in bioinformatics, such as detecting differentially expressed genes or CpG sites, are population-based and therefore do not effectively model intersample diversity. Here we introduce a unified theory to quantify sample-level heterogeneity that is applicable to a single omics profile. Specifically, we simplify an omics profile to a digital representation based on the omics profiles …

Driver Fusions And Their Implications In The Development And Treatment Of Human Cancers., Qingsong Gao, Wen-Wei Liang, Steven M Foltz, Gnanavel Mutharasu, Reyka G Jayasinghe, Song Cao, Wen-Wei Liao, Sheila M Reynolds, Matthew A Wyczalkowski, Lijun Yao, Lihua Yu, Sam Q Sun, Ken Chen, Alexander J Lazar, Ryan C Fields, Michael C Wendl, Brian A Van Tine, Ravi Vij, Feng Chen, Matti Nykter, Ilya Shmulevich, Li Ding

Articles, Abstracts, and Reports

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of …