Medical Specialties Commons^™

A Protocol For Prospective Studies" "5-Hydroxyvitamin D, Leptin And B Ass Index In Relation To Cutaneou Elanoma Incidence And Survival, Jo S. Stenehjem, Tom K. Grimsrud, Judy R. Rees, Linda Vos, Ronnie Babigumira, Marit B. Veierød, Trude E. Robsahm

Dartmouth Scholarship

Introduction The incidence and mortality rates of

cutaneous melanoma (CM) are increasing among fai skinned populations worldwide. Ultraviolet radiation s the principal risk factor for CM, but is also the mai source of 25-hydroxyvitamin D (25(OH)D), which has associated with reduced risk and better prognosis of cancer types. However, both low and high 25(OH)D l have been associated with increased risk of CM. Obe as measured by body mass index (BMI) is associated risk of several cancers and has also been suggested risk factor for CM, and may also be related to insuffi 25(OH)D and/or high leptin levels. Moreover, contract …

Igf2 Mrna Binding Protein 3 (Imp3) Promotes Glioma Cell Migration By Enhancing The Translation Of Rela/P65., Shruti Bhargava, Abhirami Visvanathan, Vikas Patil, Anuj Kumar, Santosh Kesari, Saumitra Das, Alangar S Hegde, Arimappamagan Arivazhagan, Vani Santosh, Kumaravel Somasundaram

Articles, Abstracts, and Reports

The diffusely infiltrative nature of glioblastoma (GBM) makes them highly recurrent. IGF2 mRNA-binding protein 3 (IMP3), a GBM upregulated RNA binding protein, promotes glioma cell migration. An integrative bioinformatics analysis identified p65 (RELA), a subunit of NF-κB heterodimer as a target and an important mediator of IMP3 promoted glioma cell migration. IMP3 increased p65 protein levels without any change in p65 transcript levels, but promoted its polysome association. RIP-PCR demonstrated the binding of IMP3 to p65 transcript. UV crosslinking experiments with in vitro transcribed RNA confirmed the specific and direct binding of IMP3 to sites on p65 3'UTR. Further, IMP3 …

Individual Patient-Level Meta-Analysis Of The Performance Of The Decipher Genomic Classifier In High-Risk Men After Prostatectomy To Predict Development Of Metastatic Disease., Daniel E. Spratt, Kasra Yousefi, Samineh Deheshi, Ashley E. Ross, Robert B. Den, Edward M. Schaeffer, Bruce J. Trock, Jingbin Zhang, Andrew G. Glass, Adam P. Dicker, Firas Abdollah, Shuang G Zhao, Lucia L.C. Lam, Marguerite Du Plessis, Voleak Choeurng, Zaid Haddad, Christine Buerki, Elai Davicioni, Sheila Weinmann, Stephen J. Freedland, Eric A. Klein, R. Jeffrey Karnes, Felix Y. Feng

Department of Radiation Oncology Faculty Papers

Purpose To perform the first meta-analysis of the performance of the genomic classifier test, Decipher, in men with prostate cancer postprostatectomy. Methods MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports between 2011 and 2016 of men treated by prostatectomy that assessed the benefit of the Decipher test. Multivariable Cox proportional hazards models fit to individual patient data were performed; meta-analyses were conducted by pooling the study-specific hazard ratios (HRs) using random-effects modeling. Extent of heterogeneity between studies was determined with the I(2) test. Results Five studies (975 total patients, and 855 patients with individual …

Genomic Classifier Augments The Role Of Pathological Features In Identifying Optimal Candidates For Adjuvant Radiation Therapy In Patients With Prostate Cancer: Development And Internal Validation Of A Multivariable Prognostic Model., Deepansh Dalela, María Santiago-Jiménez, Kasra Yousefi, R. Jeffrey Karnes, Ashley E. Ross, Robert B. Den, Stephen J. Freedland, Edward M. Schaeffer, Adam P. Dicker, Mani Menon, Alberto Briganti, Elai Davicioni, Firas Abdollah

Department of Radiation Oncology Faculty Papers

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship …

The Role Of Central Neck Lymph Node Dissection In The Management Of Papillary Thyroid Cancer., Lawrence A Shirley, Natalie B Jones, John E Phay

Oncology Articles

Papillary thyroid cancer (PTC) is the most common thyroid malignancy, and cervical nodal metastases are frequent at presentation. The most common site for nodal metastases from PTC is the central compartment of the ipsilateral neck in the paratracheal and pretracheal regions. The decision to resect these lymph nodes at the time of thyroidectomy often depends on if nodes with suspected malignancy can be identified preoperatively. If nodal spread to the central neck nodes is known, then the consensus is to remove all nodes in this area. However, there remains significant controversy regarding the utility of removing central neck lymph nodes …

Blimp-1 Impairs T Cell Function Via Upregulation Of Tigit And Pd-1 In Patients With Acute Myeloid Leukemia., Liuluan Zhu, Yaxian Kong, Jianhong Zhang, David F. Claxton, W. Christopher Ehmann, Witold B. Rybka, Neil D. Palmisiano, Ming Wang, Bei Jia, Michael Bayerl, Todd D. Schell, Raymond J. Hohl, Hui Zeng, Hong Zheng

Department of Medical Oncology Faculty Papers

BACKGROUND: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML.

METHODS: Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression was examined by flow cytometry. The correlation of …

Inhibition Of Age-Related Therapy Resistance In Melanoma By Rosiglitazone-Mediated Induction Of Klotho., Reeti Behera, Amanpreet Kaur, Marie R. Webster, Suyeon Kim, Abibatou Ndoye, Curtis H. Kugel, Gretchen M. Alicea, Joshua Wang, Kanad Ghosh, Phil Cheng, Sofia Lisanti, Katie Marchbank, Vanessa Dang, Mitchell Levesque, Reinhard Dummer, Xiaowei Xu, Meenhard Herlyn, Andrew E. Aplin, Alexander Roesch, Cecilia Caino, Dario C. Altieri, Ashani T. Weeraratna

Department of Cancer Biology Faculty Papers

Purpose: Aging is a poor prognostic factor for melanoma. We have shown that melanoma cells in an aged microenvironment are more resistant to targeted therapy than identical cells in a young microenvironment. This is dependent on age-related secreted factors. Klotho is an age-related protein whose serum levels decrease dramatically by age 40. Most studies on klotho in cancer have focused on the expression of klotho in the tumor cell. We have shown that exogenous klotho inhibits internalization and signaling of Wnt5A, which drives melanoma metastasis and resistance to targeted therapy. We investigate here whether increasing klotho in the aged microenvironment …

Treatment Pathway Of Bone Sarcoma In Children, Adolescents, And Young Adults, Damon R. Reed, Masanori Hayashi, Lars M. Wagner, Odion Binitie, Diana A. Steppan, Andrew S. Brohl, Eric T. Shinohara, Julia A. Bridge, David M. Loeb, Scott C. Borinstein, Michael S. Isakoff

Pediatrics Faculty Publications

When pediatric, adolescent, and young adult patients present with a bone sarcoma, treatment decisions, especially after relapse, are complex and require a multidisciplinary approach. This review presents scenarios commonly encountered in the therapy of bone sarcomas with the goal of objectively presenting a consensus, multidisciplinary management approach. Little variation was found in the authors' group with respect to local control or systemic therapy. Clinical trials were universally prioritized in all settings. Decisions regarding relapse therapies in the absence of a clinical trial had very minor variations initially, but a consensus was reached after a literature review and discussion. This review …

Integration Of Metabolomics, Transcriptomics, And Microrna Expression Profiling Reveals A Mir-143-Hk2-Glucose Network Underlying Zinc-Deficiency-Associated Esophageal Neoplasia, Louise Y. Fong, Ruiyan Jing, Karl Smalley, Cristian Taccioli, Johannes Fahrmann, Dinesh K. Barupal, Hansjuerg Alder, John L. Farber, Oliver Fiehn, Carlo M. Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Esophageal squamous cell carcinoma (ESCC) in humans is a deadly disease associated with dietary zinc (Zn)-deficiency. In the rat esophagus, Zn-deficiency induces cell proliferation, alters mRNA and microRNA gene expression, and promotes ESCC. We investigated whether Zn-deficiency alters cell metabolism by evaluating metabolomic profiles of esophageal epithelia from Zn-deficient and replenished rats vs sufficient rats, using untargeted gas chromatography time-of-flight mass spectrometry (n = 8/group). The Zn-deficient proliferative esophagus exhibits a distinct metabolic profile with glucose down 153-fold and lactic acid up 1.7-fold (P < 0.0001), indicating aerobic glycolysis (the "Warburg effect"), a hallmark of cancer cells. Zn-replenishment rapidly increases glucose content, restores deregulated metabolites to control levels, and reverses the hyperplastic phenotype. Integration of metabolomics and our reported transcriptomic data for this tissue unveils a link between glucose down-regulation and overexpression of HK2, an enzyme that catalyzes the first step of glycolysis and is overexpressed in cancer cells. Searching our published microRNA profile, we find that the tumor-suppressor miR-143, a negative regulator of HK2, is down-regulated in Zn-deficient esophagus. Using in situ hybridization and immunohistochemical analysis, the inverse correlation between miR-143 down-regulation and HK2 overexpression is documented in hyperplastic Zndeficient esophagus, archived ESCC-bearing Zn-deficient esophagus, and human ESCC tissues. Thus, to sustain uncontrolled cell proliferation, Zn-deficiency reprograms glucose metabolism by modulating expression of miR-143 and its target HK2. Our work provides new insight into critical roles of Zn in ESCC development and prevention. © Fong et al.

Completion Dissection Or Observation For Sentinel-Node Metastasis In Melanoma., Mark Faries, John F Thompson, Alistair J Cochran, Robert H Andtbacka, Nicola Mozzillo, Jonathan S Zager, Tiina Jahkola, Tawnya L Bowles, Alessandro Testori, Peter D Beitsch, Harald J Hoekstra, Marc Moncrieff, Christian Ingvar, Michel W J M Wouters, Michael S Sabel, Edward A Levine, Doreen Agnese, Michael Henderson, Reinhard Dummer, Carlo R Rossi, Rogerio I Neves, Steven D Trocha, Frances Wright, David R Byrd, Maurice Matter, Eddy Hsueh, Alastair Mackenzie-Ross, Douglas B Johnson, Patrick Terheyden, Adam C Berger, Tara L Huston, Jeffrey D Wayne, B Mark Smithers, Heather B Neuman, Schlomo Schneebaum, Jeffrey E Gershenwald, Charlotte E Ariyan, Darius C Desai, Lisa Jacobs, Kelly M Mcmasters, Anja Gesierich, Peter Hersey, Steven D Bines, John M Kane, Richard J Barth, Gregory Mckinnon, Jeffrey M Farma, Erwin Schultz, Sergi Vidal-Sicart, Richard A Hoefer, James M Lewis, Randall Scheri, Mark C Kelley, Omgo E Nieweg, R Dirk Noyes, Dave S B Hoon, He-Jing Wang, David A Elashoff, Robert M Elashoff

Articles, Abstracts, and Reports

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear.

METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis.

RESULTS: Immediate completion …

Obesity, Metabolic Factors And Risk Of Different Histological Types Of Lung Cancer: A Mendelian Randomization Study, Robert Carreras-Torres, Mattias Johansson, Philip C. Haycock, Kaitlin H. Wade, Caroline L. Relton, Richard M. Martin, George Davey Smith, Demetrius Albanes, Melinda C. Aldrich, Angeline Andrew, Susanne M. Arnold, Heike Bickeböller, Stig E. Bojesen, Hans Brunnström, Jonas Manjer, Irene Brüske, Neil E. Caporaso, Chu Chen, David C. Christiani, Warren Jay Christian, Jennifer A. Doherty, Eric J. Duell, John K. Field, Michael P. A. Davies, Michael W. Marcus, Gary E. Goodman, Kjell Grankvist, Aage Haugen, Yun-Chul Hong, Lambertus A. Kiemeney

Markey Cancer Center Faculty Publications

Background

Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.

Methods and findings

We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of …

Exploring Cancer Metabolism Using Stable Isotope-Resolved Metabolomics (Sirm), Ronald C. Bruntz, Andrew N. Lane, Richard M. Higashi, Teresa W. -M. Fan

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic reprogramming is a hallmark of cancer. The changes in metabolism are adaptive to permit proliferation, survival, and eventually metastasis in a harsh environment. Stable isotope-resolved metabolomics (SIRM) is an approach that uses advanced approaches of NMR and mass spectrometry to analyze the fate of individual atoms from stable isotope-enriched precursors to products to deduce metabolic pathways and networks. The approach can be applied to a wide range of biological systems, including human subjects. This review focuses on the applications of SIRM to cancer metabolism and its use in understanding drug actions.

Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations In Prostate Cancer., Alfonso Urbanucci, Stefan J. Barfeld, Ville Kytölä, Harri M. Itkonen, Ilsa M. Coleman, Daniel Vodák, Liisa Sjöblom, Xia Sheng, Teemu Tolonen, Sarah Minner, Christoph Burdelski, Kati K. Kivinummi, Annika Kohvakka, Steven Kregel, Mandeep Takhar, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Paul Lloyd, R. Jeffrey Karnes, Ashley E. Ross, Edward M. Schaeffer, Donald J. Vander Griend, Stefan Knapp, Eva Corey, Felix Y. Feng, Peter S. Nelson, Fahri Saatcioglu, Karen E. Knudsen, Teuvo L.J. Tammela, Guido Sauter, Thorsten Schlomm, Matti Nykter, Tapio Visakorpi, Ian G. Mills

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene …

Quantification And Expert Evaluation Of Evidence For Chemopredictive Biomarkers To Personalize Cancer Treatment., Shruti Rao, Robert A. Beckman, Shahla Riazi, Cinthya S. Yabar, Simina M. Boca, John L. Marshall, Michael J. Pishvaian, Jonathan R. Brody, Subha Madhavan

Department of Surgery Faculty Papers

Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines. We focused on studies that investigated changes in gene or protein expression as predictors of drug sensitivity or resistance. We considered an evidence framework that ranked studies from high level I evidence for randomized …

Intratumoral Heterogeneity Analysis Reveals Hidden Associations Between Protein Expression Losses And Patient Survival In Clear Cell Renal Cell Carcinoma., Wei Jiang, Essel Dulaimi, Karthik Devarajan, Theodore Parsons, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Stephen C. Peiper, Joseph R. Testa, Robert Uzzo, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker losses with patho-clinical parameters. Categorical variables were compared between groups …

Genome-Wide Chromatin Accessibility, Dna Methylation And Gene Expression Analysis Of Histone Deacetylase Inhibition In Triple-Negative Breast Cancer., Matias A Bustos, Matthew P Salomon, Nellie Nelson, Sandy C Hsu, Maggie L Dinome, Dave S B Hoon, Diego M Marzese

Articles, Abstracts, and Reports

Triple-negative breast cancer (TNBC), especially the subset with a basal phenotype, represents the most aggressive subtype of breast cancer. Unlike other solid tumors, TNBCs harbor a low number of driver mutations. Conversely, we and others have demonstrated a significant impact of epigenetic alterations, including DNA methylation and histone post-translational modifications, affecting TNBCs. Due to the promising results in pre-clinical studies, histone deacetylase inhibitors (HDACi) are currently being tested in several clinical trials for breast cancer and other solid tumors. However, the genome-wide epigenetic and transcriptomic implications of HDAC inhibition are still poorly understood. Here, we provide detailed information about the …

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …

Comparison Of Online 6 Degree-Of-Freedom Image Registration Of Varian Truebeam Cone-Beam Ct And Brainlab Exactrac X-Ray For Intracranial Radiosurgery., Jun Li, Wenyin Shi, David W. Andrews, Maria Werner-Wasik, Bo Lu, Yan Yu, Adam Dicker Md, Phd, Haisong Lui

Department of Radiation Oncology Faculty Papers

PURPOSE: The study was aimed to compare online 6 degree-of-freedom image registrations of TrueBeam cone-beam computed tomography and BrainLab ExacTrac X-ray imaging systems for intracranial radiosurgery.

METHODS: Phantom and patient studies were performed on a Varian TrueBeam STx linear accelerator (version 2.5), which is integrated with a BrainLab ExacTrac imaging system (version 6.1.1). The phantom study was based on a Rando head phantom and was designed to evaluate isocenter location dependence of the image registrations. Ten isocenters at various locations representing clinical treatment sites were selected in the phantom. Cone-beam computed tomography and ExacTrac X-ray images were taken when the …

Lisinopril Or Coreg Cr In Reducing Cardiotoxicity In Women With Breast Cancer Receiving Trastuzumab: A Rationale And Design Of A Randomized Clinical Trial, Maya Guglin, Pamela Munster, Angelina Fink, Jeffrey Krischer

Internal Medicine Faculty Publications

Background—Trastuzumab (TZB) is an established therapy for HER2 positive breast cancer. The use of TZB is commonly associated with cardiotoxicity manifesting as asymptomatic decrease in left ventricular ejection fraction (LVEF) or overt heart failure. Several studies demonstrated favorable effects of angiotensin converting enzyme (ACE) inhibitors and beta blockers (BB) in the prevention of chemotherapy-induced cardiotoxicity. We hypothesize that patients, randomized to receive an ACE inhibitor or a beta-blocker during trastuzumab therapy for breast cancer, will maintain a higher LVEF than patients randomized to placebo.

Methods and Results—We designed a prospective, multicenter, randomized, phase II placebo-controlled clinical trial to …

Clinicians’ Perspectives On Adopting A Lung Cancer Palliative Care Intervention, Shaunna Siler

Loma Linda University Electronic Theses, Dissertations & Projects

Despite the significant progress in implementing palliative care interventions for cancer patients, few intervention studies seek healthcare clinicians’ input prior to implementation. The purpose of this research was then to explore palliative care and oncology clinicians’ (e.g., physicians, nurses, social workers, and chaplains) perspectives on current challenges and useful practices in meeting the quality of life needs of lung cancer patients and family caregivers, and to increase the likelihood of the adoption of a palliative care intervention based on understanding current trends in palliative care delivery at three outpatient oncology sites. The conceptual framework used for this study was the …

Outcomes Of Spatially Fractionated Radiotherapy (Grid) For Bulky Soft Tissue Sarcomas In A Large Animal Model, Michael W. Nolan, Tracy L. Gieger, Alexander A. Karakashian, Mariana N. Nikolova‑Karakashian, Lysa P. Posner, Donald M. Roback, Judith N. Rivera, Sha Chang

Physiology Faculty Publications

GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade …

Diverse Expression Patterns And Tumorigenic Role Of Neurotensin Signaling Components In Colorectal Cancer Cells, Ji Tae Kim, Heidi L. Weiss, B. Mark Evers

Markey Cancer Center Faculty Publications

Colorectal cancer (CRC), which is one of the most common malignancies worldwide, results from an accumulation of genetic and epigenetic modifications including DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central nervous system, mediates its physiological and pathological effects, including growth stimulation for a variety of cancers, through three distinct NTS receptors (NTSRs). Most NTS functions are mediated through the high-affinity receptor NTSR1, and expression of NTSR1 is increased in many cancers including CRC. In this study, we investigated the expression profiles and cellular functions of the NTSRs, especially NTSR1, in CRC cells. We showed that expression …

Molecular-Based Recursive Partitioning Analysis Model For Glioblastoma In The Temozolomide Era: A Correlative Analysis Based On Nrg Oncology Rtog 0525., Erica Hlavin Bell, Stephanie L Pugh, Joseph P. Mcelroy, Mark R. Gilbert, Minesh Mehta, Alexander C Klimowicz, Anthony Magliocco, Markus Bredel, Pierre Robe, Anca L. Grosu, Roger Stupp, Walter Curran, Aline P. Becker, Andrea L. Salavaggione, Jill S. Barnholtz-Sloan, Kenneth Aldape, Deborah T. Blumenthal, Paul D. Brown, Jon Glass, Luis Souhami, R. Jeffrey Lee, David Brachman, John Flickinger, Minhee Won, Arnab Chakravarti

Department of Neurosurgery Faculty Papers

Importance: There is a need for a more refined, molecularly based classification model for glioblastoma (GBM) in the temozolomide era.

Objective: To refine the existing clinically based recursive partitioning analysis (RPA) model by incorporating molecular variables.

Design, Setting, and Participants: NRG Oncology RTOG 0525 specimens (n = 452) were analyzed for protein biomarkers representing key pathways in GBM by a quantitative molecular microscopy-based approach with semiquantitative immunohistochemical validation. Prognostic significance of each protein was examined by single-marker and multimarker Cox regression analyses. To reclassify the prognostic risk groups, significant protein biomarkers on single-marker analysis were incorporated into an RPA model …

Implementation Of Quality Measures In Site-Specific Multidisciplinary Tumour Boards, Ahmed Nadeem Abbasi, Huriye Senay Kiziltan

Department of Radiation Oncology

No abstract provided.

Targeting Ledgf/P75 To Sensitize Chemoresistant Prostate Cancer Cells To Taxanes, Leslimar Rios-Colón

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer (PCa) is the second most diagnosed cancer in males. This disease disproportionately affects African American men, with a higher incidence and mortality compared to other ethnic/racial groups. An aging male population and the complexity of addressing the health disparities associated with this disease puts PCa into the spotlight due to its serious public health implications and the imminent fiscal challenge over the next decades. Chronic prostate inflammation resulting in activation of stress and prosurvival pathways contribute to disease progression and the development of chemoresistance. Lens epithelium-derived growth factor p75 (LEDGF/p75) is a stressresponse protein that promotes cellular survival …

A Study Protocol For A Randomised Controlled Trial Of An Interactive Web-Based Intervention: Cancercope, Suzanne K. Chambers, Lee Ritterband, Frances Thorndike, Lisa Nielsen, Joanne Aitken, Samantha Clutton, Paul Scuffham, Philippa Youl, Bronwyn Morris, Peter Baade, Jeffrey Dunn

Research outputs 2014 to 2021

Introduction:

Approximately 35% of patients with cancer experience clinically significant distress, and unmet psychological supportive care needs are prevalent. This study describes the protocol for a randomised controlled trial (RCT) to assess the efficacy and cost-effectiveness of an internet-based psychological intervention for distressed patients with cancer.

Methods and analysis:

In phase I, the intervention was developed on an interactive web platform and pilot tested for acceptability using a qualitative methodology with 21 patients with cancer. Phase II is an RCT underway with patients with or at risk of elevated psychological distress comparing: (1) static patient education website with (2) …

Firing Up Instead Of Burning Out: Tales From The Front Line Of The Cake Committee, Britainy Stephens, Msw, Lsw, Lora Rhodes, Msw, Lsw, Alison Petok, Msw, Lcsw, Gregory Garber, Msw, Lcsw

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

This presentation will focus on an underutilized model of supportive care that can help bring back some of the human moments that can often be lost in delivering supportive oncology care. Handling the often complicated issues that arise in oncology care can take a toll on social workers and our oncology co-workers in other disciplines. In oncology care, especially in an outpatient setting, social workers often fulfill the role of emotional support not just for our patients but also for other oncology professionals. Though we are not employed to act as such, we dually assume the position of therapist and …

Potent Anti-Cancer Effects Of Less Polar Curcumin Analogues On Gastric Adenocarcinoma And Esophageal Squamous Cell Carcinoma Cells, Fatemeh Alibeiki, Naser Jafari, Maryam Karimi, Hadi Peeri Dogaheh

Markey Cancer Center Faculty Publications

Curcumin and its chalcone derivatives inhibit the growth of human cancer cells. It is reported that replacement of two OH groups in curcumin with less polar groups like methoxy increases its anti-proliferative activity. In this study, we explored benzylidine cyclohexanone derivatives with non-polar groups, to see if they possess increased anti-cancer activity. Novel 2,6-bis benzylidine cyclohexanone analogues of curcumin were synthesized, and their inhibitory effects on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cancer cells were studied using an MTT assay. Cell apoptosis was detected by EB/AO staining, and cell cycle was analyzed by flow cytometry. Real-time PCR …

Can Exercise Suppress Tumour Growth In Advanced Prostate Cancer Patients With Sclerotic Bone Metastases? A Randomised, Controlled Study Protocol Examining Feasibility, Safety And Efficacy, Nicolas H. Hart, Robert Newton, Nigel Spry, Dennis Taaffe, Suzanne K. Chambers, Kynan Feeney, David Joseph, Andrew D. Redfern, Tom Ferguson, Daniel A. Galvao

Research outputs 2014 to 2021

Introduction

Exercise may positively alter tumour biology through numerous modulatory and regulatory mechanisms in response to a variety of modes and dosages, evidenced in preclinical models to date. Specifically, localised and systemic biochemical alterations produced during and following exercise may suppress tumour formation, growth and distribution by virtue of altered epigenetics and endocrine–paracrine activity. Given the impressive ability of targeted mechanical loading to interfere with metastasis-driven tumour formation in human osteolytic tumour cells, it is of equal interest to determine whether a similar effect is observed in sclerotic tumour cells. The study aims to (1) establish the feasibility and safety …

Frameless Image-Guided Radiosurgery For Trigeminal Neuralgia, Lisa B. E. Shields, Todd S. Shanks, Andrew J. Shearer, Lauren A. Shelton, Brent J. Shelton, Jonathan Howe, James M. Coons, Brian Plato, Aaron C. Spalding

Markey Cancer Center Faculty Publications

Background: Frameless image-guided radiosurgery (IGRS) is a safe and effective noninvasive treatment for trigeminal neuralgia (TN). This study evaluates the use of frameless IGRS to treat patients with refractory TN.

Methods: We reviewed the records of 20 patients diagnosed with TN who underwent frameless IGRS treatments between March 2012 and December 2013. Facial pain was graded using the Barrow Neurological Institute (BNI) scoring system. The initial setup uncertainty from simulation to treatment and the patient intrafraction uncertainty were measured. The median follow-up was 32 months.

Results: All patients' pain was BNI Grade IV or V before the frameless IGRS treatment. …