Medicine and Health Sciences Commons^™

Epigenetic Regulation During Cancer Transitions Across 11 Tumour Types, Nadezhda V Terekhanova, Alla Karpova, Wen-Wei Liang, Siqi Chen, Yize Li, Austin N Southard-Smith, Michael D Iglesia, Michael C Wendl, Reyka G Jayasinghe, Jingxian Liu, Yizhe Song, Song Cao, Andrew Houston, Xiuting Liu, Matthew A Wyczalkowski, Rita Jui-Hsien Lu, Wagma Caravan, Andrew Shinkle, Nataly Naser Al Deen, John M Herndon, Jacqueline Mudd, Kazuhito Sato, Omar M Ibrahim, Chia-Kuei Mo, Sara E Chasnoff, Jason M Held, Russell Pachynski, Julie K Schwarz, William E Gillanders, Albert H Kim, Ravi Vij, John F Dipersio, Sidharth V Puram, Milan G Chheda, Katherine C Fuh, David G Denardo, Ryan C Fields, Feng Chen, Li Ding, Et Al.

2020-Current year OA Pubs

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis

Mitochondrial Rna Modifications Shape Metabolic Plasticity In Metastasis, Sylvain Delaunay, Gloria Pascual, Bohai Feng, Kevin Klann, Mikaela Behm, Agnes Hotz-Wagenblatt, Karsten Richter, Karim Zaoui, Esther Herpel, Christian Münch, Sabine Dietmann, Jochen Hess, Salvador Aznar Benitah, Michaela Frye

2020-Current year OA Pubs

Aggressive and metastatic cancers show enhanced metabolic plasticity

Characterization Of The Genomic And Immunologic Diversity Of Malignant Brain Tumors Through Multisector Analysis, Maximilian O Schaettler, Megan M Richters, Anthony Z Wang, Zachary L Skidmore, Bryan Fisk, Albert H Kim, Michael R Chicoine, Joshua W Osbun, Eric C Leuthardt, Joshua L Dowling, Gregory J Zipfel, Ralph G Dacey, Hsiang-Chih Lu, Tanner M Johanns, Obi L Griffith, Malachi Griffith, Gavin P Dunn, Et Al.

2020-Current year OA Pubs

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen …

Phase I Study Of Single Agent Niz985, A Recombinant Heterodimeric Il-15 Agonist, In Adult Patients With Metastatic Or Unresectable Solid Tumors, Kevin Conlon, Andrea Wang-Gillam, Et Al

2020-Current year OA Pubs

BACKGROUND: NIZ985 is a recombinant heterodimer of physiologically active interleukin (IL-)15 and IL-15 receptor alpha. In preclinical models, NIZ985 promotes cytotoxic lymphocyte proliferation, killing function, and organ/tumor infiltration, with resultant anticancer effects. In this first-in-human study, we assessed the safety, pharmacokinetics, and immune effects of NIZ985 in patients with metastatic or unresectable solid tumors.

METHODS: Single agent NIZ985 dose escalation data are reported from a phase I dose escalation/expansion study of NIZ985 as monotherapy. Adult patients (N=14) received 0.25, 0.5, 1, 2 or 4 µg/kg subcutaneous NIZ985 three times weekly (TIW) for the first 2 weeks of each 28-day cycle, …

Il-7 Expands Lymphocyte Populations And Enhances Immune Responses To Sipuleucel-T In Patients With Metastatic Castration-Resistant Prostate Cancer (Mcrpc), Russell K Pachynski, Chihiro Morishima, Et Al

2020-Current year OA Pubs

BACKGROUND: Sipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP).

METHODS: Fifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using …

Tumor-On-Chip Modeling Of Organ-Specific Cancer And Metastasis, Nuala Del Piccolo, Venktesh S Shirure, Ye Bi, S Peter Goedegebuure, Sepideh Gholami, Christopher C W Hughes, Ryan C Fields, Steven C George

2020-Current year OA Pubs

Every year, cancer claims millions of lives around the globe. Unfortunately, model systems that accurately mimic human oncology - a requirement for the development of more effective therapies for these patients - remain elusive. Tumor development is an organ-specific process that involves modification of existing tissue features, recruitment of other cell types, and eventual metastasis to distant organs. Recently, tissue engineered microfluidic devices have emerged as a powerful in vitro tool to model human physiology and pathology with organ-specificity. These organ-on-chip platforms consist of cells cultured in 3D hydrogels and offer precise control over geometry, biological components, and physiochemical properties. …

Optimized Polyepitope Neoantigen Dna Vaccines Elicit Neoantigen-Specific Immune Responses In Preclinical Models And In Clinical Translation, Lijin Li, Xiuli Zhang, Xiaoli Wang, Samuel W Kim, John M Herndon, Michelle K Becker-Hapak, Beatriz M Carreno, Nancy B Myers, Mark A Sturmoski, Michael D Mclellan, Christopher A Miller, Tanner M Johanns, Benjamin R Tan, Gavin P Dunn, Timothy P Fleming, Ted H Hansen, S Peter Goedegebuure, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation.

METHODS: We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer …

Relationship Between Clinicopathologic Factors And Fdg Avidity In Radioiodine-Negative Recurrent Or Metastatic Differentiated Thyroid Carcinoma, Le Ngoc Ha, Amir Iravani, Nguyen Thi Nhung, Ngo Thi Minh Hanh, Febby Hutomo, Mai Hong Son

2020-Current year OA Pubs

BACKGROUND: In this study, we investigated the relationship between clinicopathologic factors, BRAF

METHODS: From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAF

RESULTS: Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17-81) were included. The majority of patients had BRAF

CONCLUSION: The majority of recurrent or metastatic RAI-negative DTC have BRAF