Digital Commons Network^™

Nano-Pulse Stimulation For The Treatment Of Pancreatic Cancer And The Changes In Immune Profile, Sigi Guo, Niculina I. Burcus, James Hornef, Yu Jing, Chunqi Jiang, Richard Heller, Stephen J. Beebe

Bioelectrics Publications

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to …

Sarcopenia During Neoadjuvant Therapy For Oesophageal Cancer: Characterising The Impact On Muscle Strength And Physical Performance, E.M. Guinan, Suzanne Doyle, A.E. Bennett, L. O'Neill, J. Gannon, J.A. Elliott, J. O'Sullivan, J.V. Reynolds, J. Hussey

Articles

Purpose Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC.

Methods Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle …

Sb Driver Analysis: A Sleeping Beauty Cancer Driver Analysis Framework For Identifying And Prioritizing Experimentally Actionable Oncogenes And Tumor Suppressors, Justin Y. Newberg, Michael A. Black, Nancy A. Jenkins, Neal G. Copeland, Karen M. Mann, Michael B. Mann

Oncologic Sciences Faculty Publications

Cancer driver prioritization for functional analysis of potential actionable therapeutic targets is a significant challenge. Meta-analyses of mutated genes across different human cancer types for driver prioritization has reaffirmed the role of major players in cancer, including KRAS, TP53 and EGFR, but has had limited success in prioritizing genes with non-recurrent mutations in specific cancer types. Sleeping Beauty (SB) insertional mutagenesis is a powerful experimental gene discovery framework to define driver genes in mouse models of human cancers. Meta-analyses of SB datasets across multiple tumor types is a potentially informative approach to prioritize drivers, and complements efforts …

Overexpression Of Egfr In Oral Premalignant Lesions And Oscc And Its Impact On Survival And Recurrence, Yumna Mirza, Syed Adnan Ali, Mohammad Sohail Awan, Romana Idress, Sana Naeem, Nida Zahid, Urooj Qadeer

Department of Surgery

Introduction: Oral squamous cell carcinoma (OSCC) the sixth leading cancer worldwide ranks as the most common cancer in males, and the third most common in females in Pakistan. It is influenced by risk factors which are widely consumed in our population. The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that is imperative for cell signalling, growth and differentiation. It is mutated and overexpressed in a variety of cancers, while in OSCC it has been linked to poor patient survival; premalignant to malignant transformation and recurrence. This study investigates the use of EGFR as a prognostic factor …

Personalizing Radiation Treatment Delivery In The Management Of Breast Cancer, Kamran A. Ahmed, G. Daniel Grass, Amber G. Orman, Casey Liveringhouse, Michael E. Montejo, Hatem H. Soliman, Heather S. Han, Brian J. Czerniecki, Javier F. Torres-Roca, Roberto Diaz

Oncologic Sciences Faculty Publications

Long-term data establishes the efficacy of radiotherapy in the adjuvant management of breast cancer. New dose and fractionation schemas have evolved and are available, each with unique risks and rewards. Current efforts are ongoing to tailor radiotherapy to the unique biology of breast cancer. In this review, we discuss our efforts to personalize radiotherapy dosing using genomic data and the implications for future clinical trials. We also explore immune mechanisms that may contribute to a tumor’s unique radiation sensitivity or resistance.

Hybrid Capture–Based Genomic Profiling Of Circulating Tumor Dna From Patients With Advanced Cancers Of The Gastrointestinal Tract Or Anus, A. B. Schrock, D. Pavlick, S. J. Klempner, J. H. Chung, B. Forcier, A. Welsh, L. Young, B. Leyland-Jones, C. Devoe, V. A. Miller, +9 Additional Authors

Journal Articles

© 2018 American Association for Cancer Research. Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal and anal cancers is increasingly used to inform treatment. In some cases, tissue biopsy can be prohibitive, and we sought to investigate whether analysis of blood-derived circulating tumor DNA (ctDNA) may provide a minimally invasive alternative. Experimental Design: Hybrid capture–based genomic profiling of 62 genes was performed on blood-based ctDNA from 417 patients with gastrointestinal carcinomas to assess the presence of genomic alterations (GA) and compare with matched tissue samples. Results: Evidence of ctDNA was detected in 344 of 417 samples (82%), and of …

Cpx-351 (Cytarabine And Daunorubicin) Liposome For Injection Versus Conventional Cytarabine Plus Daunorubicin In Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia, J. E. Lancet, G. L. Uy, J. E. Cortes, L. F. Newell, T. L. Lin, E. K. Ritchie, R. K. Stuart, S. A. Strickland, J. E. Kolitz, B. C. Medeiros, +11 Additional Authors

Journal Articles

© 2018 by American Society of Clinical Oncology. Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of …

Extended Follow-Up And Impact Of High-Risk Prognostic Factors From The Phase 3 Resonate Study In Patients With Previously Treated Cll/Sll, J. R. Brown, P. Hillmen, S. O'Brien, J. C. Barrientos, N. M. Reddy, S. E. Coutre, C. S. Tam, S. P. Mulligan, U. Jaeger, J. C. Byrd, +20 Additional Authors

Journal Articles

No abstract provided.

Activity Of Pazopanib And Trabectedin In Advanced Alveolar Soft Part Sarcoma, S. Stacchiotti, O. Mir, A. Le Cesne, B. Vincenzi, A. Fedenko, R. G. Maki, N. Somaiah, S. Patel, M. Brahmi, A. Kawai, +13 Additional Authors

Journal Articles

No abstract provided.

Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong

Bioelectrics Publications

Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O₂ plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response …

Differential Presentation And Survival Of De Novo And Recurrent Metastatic Breast Cancer Over Time: 1990-2010., Judith A Malmgren, Musa Mayer, Mary K Atwood, Henry G Kaplan

Articles, Abstracts, and Reports

BACKGROUND: Differences in de novo (dnMBC) and recurrent metastatic breast cancer (rMBC) presentation and survival over time have not been adequately described.

METHODS: A retrospective cohort study, 1990-2010, with follow up through 2015 of dnMBC patients (stage IV at diagnosis) and rMBC patients with subsequent distant metastatic recurrence (stage I-III initial diagnosis) [dnMBC = 247, rMBC = 911)]. Analysis included Chi squared tests of categorical variables, Kaplan-Meier survival estimates, and Cox proportional adjusted hazard ratios (HzR) and 95% confidence intervals (CI). Disease specific survival (DSS) was time from diagnosis or distant recurrence to BC death.

RESULTS: Over time, 1990-1998, 1999-2004, …

Tumor Mutational Burden Is A Determinant Of Immune-Mediated Survival In Breast Cancer., Alexandra Thomas, Eric D Routh, Ashok Pullikuth, Guangxu Jin, Jing Su, Jeff W Chou, Katherine A Hoadley, Cristin Print, Nick Knowlton, Michael A Black, Sandra Demaria, Ena Wang, Davide Bedognetti, Wendell D Jones, Gaurav A Mehta, Michael L Gatza, Charles M Perou, David B Page, Pierre Triozzi, Lance D Miller

Articles, Abstracts, and Reports

Mounting evidence supports a role for the immune system in breast cancer outcomes. The ability to distinguish highly immunogenic tumors susceptible to anti-tumor immunity from weakly immunogenic or inherently immune-resistant tumors would guide development of therapeutic strategies in breast cancer. Genomic, transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were used to examine statistical associations between tumor mutational burden (TMB) and the survival of patients whose tumors were assigned to previously-described prognostic immune subclasses reflecting favorable, weak or poor immune-infiltrate dispositions (FID, WID or PID, respectively). …

Effectiveness Of Subcutaneously Administered Leuprolide Acetate To Achieve Low Nadir Testosterone In Prostate Cancer Patients., Christopher M Pieczonka, Przemyslaw Twardowski, Joseph Renzulli, Jason Hafron, Deborah M Boldt-Houle, Stuart Atkinson, Scott Eggener

Articles, Abstracts, and Reports

Evidence suggests lower nadir testosterone levels during the first year of androgen deprivation therapy improve advanced prostate cancer clinical outcomes. We evaluated pivotal trials for subcutaneously administered leuprolide acetate (1-, 3-, 4-, and 6-month doses) to determine nadir testosterone levels. Pooled analysis showed 99%, 97%, and 91% of patients reached nadir testosterone ≤20, ≤10, and ≤5 ng/dL respectively (median ≤3 ng/dL). Across all available categories, $88% of patients reached nadir testosterone ≤5 ng/dL, and

Surgical Standards For Management Of The Axilla In Breast Cancer Clinical Trials With Pathological Complete Response Endpoint., Judy C Boughey, Michael D Alvarado, Rachael B Lancaster, W Fraser Symmans, Rita Mukhtar, Jasmine M Wong, Cheryl A Ewing, David A Potter, Todd M Tuttle, Tina J Hieken, Jodi M Carter, James W Jakub, Henry G Kaplan, Claire L Buchanan, Nora T Jaskowiak, Husain A Sattar, Jeffrey Mueller, Rita Nanda, Claudine J Isaacs, Paula R Pohlmann, Filipa Lynce, Eleni A Tousimis, Jay C Zeck, M Catherine Lee, Julie E Lang, Paulette Mhawech-Fauceglia, Roshni Rao, Bret Taback, Margaret Chen, Kevin M Kalinsky, Hanina Hibshoosh, Brigid Killelea, Tara Sanft, Gillian L Hirst, Smita Asare, Jeffrey B Matthews, Jane Perlmutter, Laura J Esserman

Articles, Abstracts, and Reports

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a …

Mir-29c Plays A Suppressive Role In Breast Cancer By Targeting The Timp3/Stat1/Foxo1 Pathway., Wan Li, Jie Yi, Xiangjin Zheng, Shiwei Liu, Weiqi Fu, Liwen Ren, Li Li, Dave S B Hoon, Jinhua Wang, Guanhua Du

Articles, Abstracts, and Reports

Background: miR-29c has been associated with the progression of many cancers. However, the function and mechanism of miR-29c have not been well investigated in breast cancers.

Methods: Real-time quantitative PCR was used to assess expression of miR-29c and DNMT3B mRNA. Western blot and immunochemistry were used to examine the expression of DNA methyltransferase 3B (DNMT3B) protein in breast cancer cells and tissues. The functional roles of miR-29c in breast cancer cells such as proliferation, migration, invasion, colony formation, and 3D growth were evaluated using MTT, transwell chambers, soft agar, and 3D Matrigel culture, respectively. In addition, the luciferase reporter assay …

Targeted Treatment Of Advanced Ovarian Cancer: Spotlight On Rucaparib., Diana C Pearre, Krishnansu S Tewari

Articles, Abstracts, and Reports

The last 2 years have ushered in a new era in ovarian cancer therapy with the US Food and Drug Administration's (FDA) approval of poly-ADP ribose polymerase (PARP) inhibitors (PARPi). One of the deadliest cancers that women experience, ovarian cancer, is most often diagnosed in advanced stages. Although cytoreductive surgery and (platinum/taxane-based) chemotherapy can place the majority of patients into remission, most will experience a relapse of their disease in their lifetime. This has led to studies exploring the benefits and efficacy of maintenance treatment. This review will briefly discuss the history of maintenance therapy as well as focus on …

Simulation Study Of Cdna Dataset To Investigate Possible Association Of Differentially Expressed Genes Of Human Thp1-Monocytic Cells In Cancer Progression Affected By Bacterial Shiga Toxins., Syed A Muhammad, Jinlei Guo, Thanh M Nguyen, Xiaogang Wu, Baogang Bai, X Frank Yang, Jake Y Chen

Articles, Abstracts, and Reports

Shiga toxin (Stxs) is a family of structurally and functionally related bacterial cytotoxins produced by Shigella dysenteriae serotype 1 and shigatoxigenic group of Escherichia coli that cause shigellosis and hemorrhagic colitis, respectively. Until recently, it has been thought that Stxs only inhibits the protein synthesis and induces expression to a limited number of genes in host cells, but recent data showed that Stxs can trigger several signaling pathways in mammalian cells and activate cell cycle and apoptosis. To explore the changes in gene expression induced by Stxs that have been shown in other systems to correlate with cancer progression, we …

Earle A. Chiles Research Institute 2017 Year In Review, Earle A. Chiles Research Institute

Articles, Abstracts, and Reports

2017 Year in Review for the Earle A. Chiles Research Institute, a division of Providence Cancer Institute at the Robert W. Franz Cancer Center. Year in Review is published annually and highlights translational immunotherapy research from the Earle A. Chiles Research Institute.

A leader in cancer immunotherapy research and innovation since 1993, the Earle A. Chiles Research Institute is a world-class research facility, and home to a team of internationally known scientists and physicians.

Patient-Reported Outcomes In A Phase Ii, North American Study Of Alectinib In Patients With Alk-Positive, Crizotinib-Resistant, Non-Small Cell Lung Cancer., Sai-Hong Ignatius Ou, Mark A Socinski, Shirish Gadgeel, Leena Gandhi, Howard West, Alberto Alejandro Chiappori, Victor Cohen, Gregory J Riely, Vlatka Smoljanovic, Walter Bordogna, Elaine Wright, Kendra Debusk, Ali Zeaiter, Alice T Shaw

Articles, Abstracts, and Reports

Background: In a phase II North American study (NP28761; NCT01871805), the anaplastic lymphoma kinase (ALK) inhibitor alectinib demonstrated both systemic and central nervous system (CNS) efficacy with good tolerability in patients with

Patients and methods: PROs and health-related quality of life (HRQoL) benefits were assessed using two self-administered questionnaires (the European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire-Core (EORTC QLQ-C30), and the 13-item EORTC QLQ-lung cancer-specific module) at enrolment and every 6 weeks until week 66, disease progression or death.

Results: Clinically meaningful mean improvements (≥10 point change from baseline) were observed in 10 domains, …

Tissue Specific Origin, Development, And Pathological Perspectives Of Pericytes., Tomoko Yamazaki, Yoh-Suke Mukouyama

Articles, Abstracts, and Reports

Pericytes are mural cells surrounding blood vessels, adjacent to endothelial cells. Pericytes play critical roles in maturation and maintenance of vascular branching morphogenesis. In the central nervous system (CNS), pericytes are necessary for the formation and regulation of the blood-brain barrier (BBB) and pericyte deficiency accompanies CNS diseases including multiple sclerosis, diabetic retinopathy, neonatal intraventricular hemorrhage, and neurodegenerative disorders. Despite the importance of pericytes, their developmental origins and phenotypic diversity remain incompletely understood. Pericytes express multiple markers and the origin of pericytes differs by tissue, which may cause difficulty for the identification and understanding of the ontogeny of pericytes. Also, …