Medical Specialties Commons^™

Integrating Art And Narrative To Enhance Quality Of Life In Palliative Care, Jennifer Fortuna

The Open Journal of Occupational Therapy

Lacie Lee Wallace, a mixed-media artist from Wheeling, West Virginia, is featured on the cover of the Fall 2018 issue of The Open Journal of Occupational Therapy (OJOT). The photograph depicts Lacie holding a self-portrait painted by artist CeCey Rose. Lacie’s physical appearance in the photograph is strikingly different from the physical appearance of the woman featured in the painting. The portrait was created 4 years before Lacie was diagnosed with advanced stage colon cancer. In the year following the diagnosis, Lacie lost nearly 100 lbs. as a result of an aggressive treatment regimen. When the palliative care team at …

Evaluating The Potential Benefit Of Reduced Planning Target Volume Margins For Low And Intermediate Risk Patients With Prostate Cancer Using Real-Time Electromagnetic Tracking., Avinash R Chaurasia, Kelly J Sun, Christopher Premo, Timothy Brand, Brent Tinnel, Stacie Barczak, John Halligan, Michael Brown, Dusten Macdonald

Articles, Abstracts, and Reports

Purpose: The aim of this study is to quantify and describe the feasibility, clinical outcomes, and patient-reported outcomes of reduced planning target volume (PTV) margins for prostate cancer treatment using real-time, continuous, intrafraction monitoring with implanted radiation frequency transponder beacons.

Methods and materials: For this prospective, nonrandomized trial, the Calypso localization system was used for intrafraction target localization in 31 patients with a PTV margin reduced to 2 mm in all directions. A total of 1333 fractions were analyzed with respect to movement of the prostate, pauses and interruptions, and dosimetric data. Pre- and posttreatment quality-of-life scores were tracked at …

The Oncogenic Roles Of Nuclear Receptor Coactivator 1 In Human Esophageal Carcinoma, Lu Wang, Weiwei Li, Kai Li, Yi Guo, Ditian Liu, Zhimeng Yao, Xianjie Lin, Shujun Li, Zuojie Jiang, Qing Liu, Yi Jiang, Beien Zhang, Lei Chen, Fuyou Zhou, Hongzheng Ren, Danxia Lin, Dianzheng Zhang, Sai-Ching Jim Yeung, Hao Zhang

PCOM Scholarly Works

Nuclear receptor coactivator 1 (NCOA1) plays crucial roles in the regulation of gene expression mediated by a wide spectrum of steroid receptors such as androgen receptor (AR), estrogen receptor α (ER α), and estrogen receptor β (ER β). Therefore, dysregulations of NCOA1 have been found in a variety of cancer types. However, the clinical relevance and the functional roles of NCOA1 in human esophageal squamous cell carcinoma (ESCC) are less known. We found in this study that elevated levels of NCOA1 protein and/or mRNA as well as amplification of the NCOA1 gene occur in human ESCC. Elevated levels of NCOA1 …

The Write Stuff - Autumn 2018 (Vol.15, No.4), Research Medical Library

Write Stuff 2018

No abstract provided.

A Systematic Review Of Treating Recurrent Head And Neck Cancer: A Reintroduction Of Brachytherapy With Or Without Surgery., Julianna Rodin, Voichita Bar-Ad, David Cognetti, Joseph Curry, Jennifer Johnson, Chad Zender, Laura Doyle, David Kutler, Benjamin E. Leiby, William M. Keane, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Purpose: To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates.

Material and methods: A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting.

Results: Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, …

Synthetic Dna Immunotherapy In Biochemically Relapsed Prostate Cancer, N. Shore, E. I. Heath, L. T. Nordquist, H. Cheng, K. Bhatt, M. Morrow, T. Mcmullan, K. Kraynyak, J. Lee, B. Sacchetta, L. Liu, S. Rosencranz, S. T. Tagawa, L. J. Appleman, R. Tutrone, J. Garcia, Y. Whang, W. Kelly, I. Csiki, M. L. Bagarazzi

Department of Medical Oncology Faculty Papers

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts).

Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) >3 months (mos), testosterone >150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM …

Exploring Optimal Sequencing Of Radiation And Immunotherapy Combinations., Andrew J Gunderson, Kristina H Young

Articles, Abstracts, and Reports

Purpose: The purpose of this article is to assemble, review, and provide a synopsis of the historical and current literature regarding optimal sequencing of radiation (RT) and immunotherapy combination treatments.

Materials and methods: A review of the literature was performed using PubMed with the query "radiation" and "Immunotherapy", "PD1", "PDL1", "CTLA4", "OX40", "checkpoint", "vaccine", "macrophage", "STING", and "TGFbeta". Studies that included sequencing of therapy were evaluated and the studies were included at the authors discretion.

Results: A paucity of primary literature exists examining the best order of radiation and immunotherapy, most of which was performed in the pre-clinical setting. The …

Stress Fractures Of The Elbow In The Throwing Athlete: A Systematic Review., Shelby R. Smith, Nirav K. Patel, Alex E. White, Christopher J Hadley, Christopher C. Dodson

Rothman Institute Papers

Background: Stress fractures of the elbow are rare in throwing athletes and present a challenge from both a management and rehabilitation perspective. Although the incidence of stress fractures of the elbow is increasing, there is a lack of data in the literature focused on throwers.

Purpose: To evaluate studies regarding the management and outcomes of stress fractures of the elbow in throwing athletes.

Study Design: Systematic review; Level of evidence, 4.

Methods: A systematic review was conducted by searching the Scopus, PubMed, and Cochrane Library electronic databases to identify studies reporting on the management and outcomes of stress fractures in …

Membrane Associated Collagen Xiii Promotes Cancer Metastasis And Enhances Anoikis Resistance, Hui Zhang, Tricia Fredericks, Gaofeng Xiong, Yifei Qi, Piotr G. Rychahou, Jia-Da Li, Taina Pihlajaniemi, Wei Xu, Ren Xu

Markey Cancer Center Faculty Publications

Background: Increased collagen expression and deposition are associated with cancer progression and poor prognosis in breast cancer patients. However, function and regulation of membrane-associated collagen in breast cancer have not been determined. Collagen XIII is a type II transmembrane protein within the collagen superfamily. Experiments in tissue culture and knockout mouse models show that collagen XIII is involved in cell adhesion and differentiation of certain cell types. In the present study, we determined roles of collagen XIII in breast cancer progression and metastasis.

Methods: We analyzed the association of collagen XIII expression with breast cancer development and metastasis using published …

Clinical Framework For Quality Improvement Of Cancer Cachexia., Clara Granda-Cameron, Mary Pat Lynch

College of Nursing Faculty Papers & Presentations

The objective of this article is to introduce the Clinical Framework for Quality Improvement of Cancer Cachexia (Cachexia Care Framework) as a tool to demonstrate the relevance of integrating the clinical components of cancer cachexia and the organizational strategies of a cancer institution on the quality of patient care and delivery of services throughout the cancer cachexia continuum. The data sources included peer-reviewed literature relevant to cancer cachexia and quality cancer care, and the authors' expertise. The Cachexia Care Framework results from a combination of the international consensus definition of cancer cachexia, the Institute of Medicine report Ensuring Quality Cancer …

Treatment-Related Decisional Conflict, Quality Of Life, And Comorbidity In Older Adults With Cancer., Jeannette M. Kates

College of Nursing Faculty Papers & Presentations

Objective: The present study aims to examine the relationships between and among cancer treatment-related decisional conflict, quality of life, and comorbidity in older adults with cancer.

Methods: A convenience sample of 200 older adults was recruited from outpatient medical oncology and radiation oncology practices in the northeastern United States. A cross-sectional, descriptive, correlational study design was used employing a survey method. Survey instruments included the Decisional Conflict scale (DCS) (with five subscales, including informed, values clarity, support, uncertainty, and effective decision); Self-administered comorbidity questionnaire (SCQ); European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (including five function …

Larotrectinib Efficacy And Safety In Trk Fusion Cancer: An Expanded Clinical Dataset Showing Consistency In An Age And Tumor Agnostic Approach, U. N. Lassen, C. M. Albert, S. Kummar, C. M. Van Tilburg, S. G. Dubois, B. Geoerger, L. Mascarenhas, N. Federman, R. J. Schilder, F. Doz, J. D. Berlin, D. Y. Oh, S. S. Bielack, R. Mcdermott, D. S. Tan, S. Cruickshank, N. C. Ku, M. C. Cox, A. Drilon, D. S. Hong

Department of Medical Oncology Faculty Papers

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19^thFeb 2018.

Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials …

Nci-Match Arms N & P: Phase Ii Study Of Pi3k Beta Inhibitor Gsk2636771 In Patients (Pts) With Cancers (Ca) With Pten Mutation/Deletion (Mut/Del) Or Pten Protein Loss, F. Janku, O. Jegede, S. L. Puhalla, P. Konstantinopoulos, F. Meric-Bernstam, E. P. Mitchell, J. A. Zwiebel, L. M. Mcshane, S. Li, L. V. Rubinstein, L. A. Doyle, D. Patton, B. A. Conley, P. J. O'Dwyer, L. N. Harris, C. Arteaga, P. M. Williams, S. R. Hamilton, A. P. Chen, K. T. Flaherty

Department of Medical Oncology Faculty Papers

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771.

Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete …

Pan-Squamous Genomic Profiling Stratified By Anatomic Tumor Site And Viral Association, M. Montesion, C. H. Chung, E. S. Sokol, S. A. Khan, H. Kang, L. A. Albacker, J. M. Johnson, G. M. Frampton, V. A. Miller, J. S. Ross, S. M. Ali

Department of Medical Oncology Faculty Papers

Background: Squamous cell carcinomas (SCC) have diverse anatomic etiologies but may share common genomic biomarkers. We profiled 7,871 unique SCCs across nine anatomic sites to investigate commonality in genomic alterations (GA), tumor mutational burden (TMB), human papillomavirus (HPV) association, and mutational signatures.

Methods: Tissue from over 8,100 unique SCC samples originating from nine anatomic sites (anogenital (anus, cervix, penis, vagina, vulva), esophagus, head and neck, lung, and skin) were sequenced by hybrid capture-based comprehensive genomic profiling to evaluate GA and TMB. About 3% of non-cutaneous SCC samples had UV signatures, indicative of potential primary site misdiagnoses, and were filtered from …

Androgen Decline And Outcome In Castration Resistant Prostate Cancer(Mcrpc) Patients Treated With Docetaxel (Doc), Prednisone1/-Bevacizumab (B), C. J. Ryan, S. Dutta, W. Kelly, M. J. Morris, M-E. Taplin, S. Halabi

Department of Medical Oncology Faculty Papers

No abstract provided.

Consistent And Reproducible Cultures Of Large-Scale 3d Mammary Epithelial Structures Using An Accessible Bioprinting Platform, John A. Reid, Peter M. Mollica, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques.

Methods: Here, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the "self-assembly" of human mammary epithelial cells. Experimental bioprinting procedures …

A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte

Manuscripts, Articles, Book Chapters and Other Papers

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response …

Epidemiology Of Moderate Alcohol Consumption And Breast Cancer: Association Or Causation?, Samir Zakhari, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate …

Intestinal Barrier Tightening By A Cell-Penetrating Antibody To Bin1, A Candidate Target For Immunotherapy Of Ulcerative Colitis., Sunil Thomas, Kevther Hoxha, Walker Alexander, John Gilligan, Rima Dilbarova, Kelly Whittaker, Andrew Kossenkov, George C. Prendergast, James M. Mullin

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) …

Fine Mapping Of Mhc Region In Lung Cancer Highlights Independent Susceptibility Loci By Ethnicity., Aida Ferreiro-Iglesias, Corina Lesseur, James Mckay, Rayjean J Hung, Younghun Han, Xuchen Zong, David Christiani, Mattias Johansson, Xiangjun Xiao, Yafang Li, David C Qian, Xuemei Ji, Geoffrey Liu, Neil Caporaso, Ghislaine Scelo, David Zaridze, Anush Mukeriya, Milica Kontic, Simona Ognjanovic, Jolanta Lissowska, Małgorzata Szołkowska, Beata Swiatkowska, Vladimir Janout, Ivana Holcatova, Ciprian Bolca, Milan Savic, Miodrag Ognjanovic, Stig Egil Bojesen, Xifeng Wu, Demetrios Albanes, Melinda C Aldrich, Adonina Tardon, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Loic Le Marchand, Gadi Rennert, Chu Chen, Jennifer Doherty, Gary Goodman, Heike Bickeböller, H-Erich Wichmann, Angela Risch, Albert Rosenberger, Hongbing Shen, Juncheng Dai, John K Field, Michael Davies, Penella Woll, M Dawn Teare, Lambertus A Kiemeney, Erik H F M Van Der Heijden, Jian-Min Yuan, Yun-Chul Hong, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Ming-Sound Tsao, Mikael Johansson, Kjell Grankvist, Matthew B Schabath, Angeline Andrew, Eric Duell, Olle Melander, Hans Brunnström, Philip Lazarus, Susanne Arnold, Stacey Slone, Jinyoung Byun, Ahsan Kamal, Dakai Zhu, Maria Teresa Landi, Christopher I Amos, Paul Brennan

Articles, Abstracts, and Reports

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In …

Autophagosome-Based Strategy To Monitor Apparent Tumor-Specific Cd8 T Cells In Patients With Prostate Cancer, Rieneke Van De Ven, Traci L. Hilton, Hong-Ming Hu, Christopher J. Dubay, Daniel Haley, Christopher Paustian, Sachin Puri, Walter J. Urba, Brendan D. Curti, Sandra Aung, Bernard A. Fox

Articles, Abstracts, and Reports

The immune system plays an essential role in eradicating cancer in concert with various treatment modalities. In the absence of autologous tumor material, no standardized method exists to assess T cell responses against the many antigens that may serve as cancer rejection antigens. Thus, development of methods to screen for therapy-induced anti-tumor responses is a high priority that could help tailor therapy. Here we tested whether a tumor-derived antigen source called DRibbles®, which contain a pool of defective ribosomal products (DRiPs), long-lived and short-lived proteins (SLiPs) and danger-associated molecular patterns (DAMPs), can be used to identify tumor-associated antigen (TAA)-specific responses …

Fine Mapping Of Mhc Region In Lung Cancer Highlights Independent Susceptibility Loci By Ethnicity, Aida Ferreiro-Iglesias, Corina Lesseur, James Mckay, Rayjean J. Hung, Younghun Han, Xuchen Zong, David Christiani, Mattias Johansson, Xiangjun Xiao, Yafang Li, David C. Qian, Xuemei Ji, Geoffrey Liu, Neil Caporaso, Ghislaine Scelo, David Zaridze, Anush Mukeriya, Milica Kontic, Simona Ognjanovic, Jolanta Lissowska, Małgorzata Szołkowska, Beata Swiatkowska, Vladimir Janout, Ivana Holcatova, Ciprian Bolca, Milan Savic, Miodrag Ognjanovic, Stig Egil Bojesen, Xifeng Wu, Demetrios Albanes, Susanne M. Arnold

Markey Cancer Center Faculty Publications

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In …

Clear Cell Adenocarcinoma Subtype Is An Independent Predictor Of Better Survival In Patients With Lung Adenocarcinoma, Takefumi Komiya Md

PCI Publications and Projects

Background:

Clear cell adenocarcinoma (CCA) has been considered as a rare subtype of lung adenocarcinoma. However, the 2011 World Health Organization (WHO) classification of lung adenocarcinoma proposed to discontinue CCA due to lack of available data with clinical significance. The role of CCA in patient prognosis needs to be investigated by using large data sources.

Methods:

Lung adenocarcinoma patients were queried from The Surveillance, Epidemiology, and End Results Program (SEER) database and were divided into CCA and ‘not otherwise specified’ category (NOS). Cancer-specific survival was studied according to gender (male, female), age (0-69,70+), SEER specific stage A system (localized, regional …

Comprehensive Evaluation Of Treatment And Outcomes Of Low-Grade Diffuse Gliomas, Catherine R. Garcia, Stacey A. Slone, Thomas A. Pittman, William H. St. Clair, Donita D. Lightner, John L. Villano

Markey Cancer Center Faculty Publications

Background

Low-grade gliomas affect younger adults and carry a favorable prognosis. They include a variety of biological features affecting clinical behavior and treatment. Having no guidelines on treatment established, we aim to describe clinical and treatment patterns of low-grade gliomas across the largest cancer database in the United States.

Methods

We analyzed the National Cancer Database from 2004 to 2015, for adult patients with a diagnosis of World Health Organization grade II diffuse glioma.

Results

We analyzed 13,621 cases with median age of 41 years. Over 56% were male, 88.4% were white, 6.1% were black, and 7.6% Hispanic. The most …

Prothrombin Complex Concentrates Or Recombinant Factor Viia Are More Effective Than Fresh-Frozen Plasma At Lowering Inr In Patients With Liver Disease, Abel J. Ignatius

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kwon JO, MacLaren R. Comparison of fresh-frozen plasma, four-factor prothrombin complex concentrates, and recombinant factor VIIa to facilitate procedures in critically ill patients with coagulopathy from liver disease: a retrospective cohort study. Pharmacotherapy. 2016;36(10):1047-1054. doi: 10.1002/phar.1827

Oxytocin And Cancer: An Emerging Link, Ben Lerman, Trisheena Harricharran, Olorunseun O. Ogunwobi

Publications and Research

The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research …

Fructose 2,6-Bisphosphate In Cancer Cell Metabolism, Ramon Bartrons, Helga Simon-Molas, Ana Rodríguez-García, Esther Castaño, Àurea Navarro-Sabaté, Anna Manzano, Ubaldo E. Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

For a long time, pioneers in the field of cancer cell metabolism, such as Otto Warburg, have focused on the idea that tumor cells maintain high glycolytic rates even with adequate oxygen supply, in what is known as aerobic glycolysis or the Warburg effect. Recent studies have reported a more complex situation, where the tumor ecosystem plays a more critical role in cancer progression. Cancer cells display extraordinary plasticity in adapting to changes in their tumor microenvironment, developing strategies to survive and proliferate. The proliferation of cancer cells needs a high rate of energy and metabolic substrates for biosynthesis of …

A Prospective Cohort Examination Of Haematological Parameters In Relation To Cancer Death And Incidence: The Busselton Health Study, Niwansa Adris, Anita Chai Geik Chua, Matthew William Knuiman, Mark Laurence Divitini, Debbie Trinder, John K. Olynyk

Research outputs 2014 to 2021

BACKGROUND: Cancer risk is associated with serum iron levels. The aim of this study was to evaluate whether haematological parameters reflect serum iron levels and may also be associated with cancer risk.

METHODS: We studied 1564 men and 1769 women who were enrolled in the Busselton Health Study, Western Australia. Haematological parameters evaluated included haemoglobin (Hb), mean cell volume (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC) and red cell distribution width (RCDW). Statistical analyses included t-tests for quantitative variables, chi-square tests for categorical variables and Cox proportional hazards regression modelling for cancer incidence and death.

RESULTS: …

Mapk Reliance Via Acquired Cdk4/6 Inhibitor Resistance In Cancer., Renée De Leeuw, Christopher Mcnair, Matthew J. Schiewer, Neermala Poudel Neupane, Lucas J. Brand, Michael A. Augello, Zhen Li, Larry C. Cheng, Akihiro Yoshida, Sean M. Courtney, E. Starr Hazard, Gary Hardiman, Maha H. Hussain, J. Alan Diehl, Justin M. Drake, William Kevin Kelly, Karen E. Knudsen

Department of Cancer Biology Faculty Papers

Purpose: Loss of cell-cycle control is a hallmark of cancer, which can be targeted with agents, including cyclin-dependent kinase-4/6 (CDK4/6) kinase inhibitors that impinge upon the G₁-S cell-cycle checkpoint via maintaining activity of the retinoblastoma tumor suppressor (RB). This class of drugs is under clinical investigation for various solid tumor types and has recently been FDA-approved for treatment of breast cancer. However, development of therapeutic resistance is not uncommon.

Experimental Design: In this study, palbociclib (a CDK4/6 inhibitor) resistance was established in models of early stage, RB-positive cancer.

Results: This study demonstrates that acquired palbociclib resistance renders cancer …

Mir-196b Target Screen Reveals Mechanisms Maintaining Leukemia Stemness With Therapeutic Potential., Sara E. Meyer, David E. Muench, Andrew M. Rogers, Tess J. Newkold, Emily Orr, Eric O'Brien, John P. Perentesis, John G. Doench, Ashish Lal, Patrick J. Morris, Craig J. Thomas, Judy Lieberman, Edwina Mcglinn, Bruce J. Aronow, Nathan Salomonis, H. Leighton Grimes

Department of Cancer Biology Faculty Papers

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27^Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27^Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation …