Medicine and Health Sciences Commons^™

Targeting Cell Cycle And Hormone Receptor Pathways In Cancer., C E S Comstock, M A Augello, J F Goodwin, R De Leeuw, M J Schiewer, W F Ostrander, R A Burkhart, A K Mcclendon, Peter Mccue, Edouard J. Trabulsi, Costas D. Lallas, Leonard G Gomella, Md, M M Centenera, Jonathan Brody, Md, L M Butler, W D Tilley, K E Knudsen, Phd

Department of Cancer Biology Faculty Papers

The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability …

Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to …

The Third International Inflammatory Breast Cancer Conference., Kenneth L Van Golen, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

Inflammatory breast cancer (IBC) is the most aggressive and deadly form of breast cancer. Disease-specific research and conferences have been organized since 2008 with the intent to bring together experts in various disciplines. This report focus on the Third International IBC Conference held in Philadelphia on December 2012.

Feasibility Of Improving Cone-Beam Ct Number Consistency Using A Scatter Correction Algorithm., Jun Li, Weiguang Yao, Ying Xiao, Yan Yu

Department of Medicine Faculty Papers

The study was to explore the feasibility of improving cone-beam CT (CBCT) number (corresponding to the Hounsfield units in computed tomography) consistency using a scatter-correction algorithm, with the aim of using CBCT images for treatment planning with density correction. A scatter correction algorithm was applied to a Varian OBI CBCT and an Elekta XVI CBCT, and was evaluated for improving CBCT number consistency. CBCT numbers of phantom materials were compared between images with and without bolus, which introduced additional scatter, and with and without scatter correction processing. It was observed that CBCT numbers were different in the images with and …

Igf-Ir Promotes Prostate Cancer Growth By Stabilizing Α5Β1 Integrin Protein Levels., Aejaz Sayeed, Carmine Fedele, Marco Trerotola, Kirat K Ganguly, Lucia R Languino

Department of Cancer Biology Faculty Papers

Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR) mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa) cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR …

Recommendations For High-Priority Research On Cancer-Related Fatigue In Children And Adults., Andrea M. Barsevick, Michael R. Irwin, Pamela Hinds, Andrew Miller, Ann Berger, Paul Jacobsen, Sonia Ancoli-Israel, Bryce B Reeve, Karen Mustian, Ann O'Mara, Jin-Shei Lai, Michael Fisch, David Cella

Department of Medical Oncology Faculty Papers

Over the past decades, some scientific progress has been made in understanding and treating cancer-related fatigue (CRF). However, three major problems have limited further progress: lack of agreement about measurement, inadequate understanding of the underlying biology, and problems in the conduct of clinical trials for CRF. This commentary reports the recommendations of a National Cancer Institute Clinical Trials Planning Meeting and an ongoing National Cancer Institute working group to address these problems so that high-priority research and clinical trials can be conducted to advance the science of CRF and its treatment. Recommendations to address measurement issues included revising the current …

Cyclin D1 Determines Estrogen Signaling In The Mammary Gland In Vivo., Mathew C Casimiro, Chenguang Wang, Z Li, Gabriele Disante, Nicole E Willmart, Sankar Addya, Lei Chen, Yang Liu, Michael P. Lisanti, Richard Pestell

Department of Cancer Biology Faculty Papers

The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein. Although it is known that cyclin D1 regulates estrogen receptor (ER)α transactivation using heterologous reporter systems, the in vivo biological significance of cyclin D1 to estrogen-dependent signaling, and the molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated. Herein, genome-wide expression profiling conducted of 17β-estradiol-treated castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1 determines estrogen-dependent gene expression for 88% of estrogen-responsive genes in vivo. In addition, expression profiling of 17β-estradiol-stimulated cyclin …

Oncogenes And Inflammation Rewire Host Energy Metabolism In The Tumor Microenvironment: Ras And Nfκb Target Stromal Mct4., Ubaldo E. Martinez-Outshoorn, Md, Joseph Curry, Md, Ying-Hui Ko, Md, Zhao Lin, Md, Madalina Tuluc, Md, David Cognetti, Md, Ruth Birbe, Md, Edmund A. Pribitkin, Md, Alessandro Bombonati, Richard Pestell, Md, Anthony Howell, Federica Sotgia, Michael P. Lisanti, Md

Kimmel Cancer Center Faculty Papers

Here, we developed a model system to evaluate the metabolic effects of oncogene(s) on the host microenvironment. A matched set of "normal" and oncogenically transformed epithelial cell lines were co-cultured with human fibroblasts, to determine the "bystander" effects of oncogenes on stromal cells. ROS production and glucose uptake were measured by FACS analysis. In addition, expression of a panel of metabolic protein biomarkers (Caveolin-1, MCT1, and MCT4) was analyzed in parallel. Interestingly, oncogene activation in cancer cells was sufficient to induce the metabolic reprogramming of cancer-associated fibroblasts toward glycolysis, via oxidative stress. Evidence for "metabolic symbiosis" between oxidative cancer cells …

Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks

Summer Training Program in Cancer Immunotherapy

Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person's life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer …

Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo

Summer Training Program in Cancer Immunotherapy

The mechanism by which the hapten 2,4-dinitrophenyl (DNP) mediates cell death is unclear according to current literature. To determine how DNP mediates death in the B16F10 murine melanoma cell line in vitro, cells were modified with 2,4-dinitro-1-fluorobenzene (DNFB). Following modification, cell lysates were collected and analyzed via Western blottings with known apoptotic or necrotic markers. Our results indicated that DNFB treated cells do not express the apoptotic marker Cleaved Caspase-3 and have no change in levels of the necrotic marker Cyclophilin A. We conclude that DNFB is not inducing apoptosis in B16F10 cells. Future research will further examine the …

A Statement On Vemurafenib-Resistant Melanoma., Edward J Hartsough, A E Aplin

Department of Cancer Biology Faculty Papers

Despite recent advancements in the treatment of late-stage mutant BRAF (V600E/K) melanomas, a major hurdle continues to be acquired resistance to BRAF inhibitors such as vemurafenib. The mechanisms for resistance have proven to be heterogeneous, emphasizing the need to use broad therapeutic approaches. In this issue, the study "Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas" by Liu et al. proposes that signal transducer and activator of transcription 3 (STAT3)-paired box 3 (PAX3) signaling may be a mechanism that is used by melanomas to resist RAF inhibitors.

Failure Patterns In Resected Pancreas Adenocarcinoma: Lack Of Predicted Benefit To Smad4 Expression., Jordan M. Winter, Laura H. Tang, David S. Klimstra, Weiguo Liu, Irena Linkov, Murray F. Brennan, Michael I. DʼAngelica, Ronald P. Dematteo, Yuman Fong, William R. Jarnagin, Eileen M. OʼReilly, Peter J. Allen

Department of Surgery Faculty Papers

OBJECTIVE: To determine whether SMAD4 expression is associated with recurrence pattern after resection for pancreatic ductal adenocarcinoma (PDA).

BACKGROUND: SMAD4 expression status has been reported to be associated with patterns of failure in PDA, but studies have not examined recurrence patterns after resection.

METHODS: A tissue microarray was constructed including 127 patients with resected PDA and either short-term (<12 >months) or long-term (>30 months) survival. SMAD4 expression was evaluated by immunohistochemistry and categorized as present or lost in tumor cells. Conventional pathologic features (lymph node metastases, positive resection margin, poor grade, and tumor size) were recorded, and disease-specific outcomes …

Cancer Metabolism: New Validated Targets For Drug Discovery., Federica Sotgia, Ubaldo E. Martinez-Outshoorn, Md, Michael P. Lisanti

Kimmel Cancer Center Faculty Papers

Recent studies in cancer metabolism directly implicate catabolic fibroblasts as a new rich source of i) energy and ii) biomass, for the growth and survival of anabolic cancer cells. Conversely, anabolic cancer cells upregulate oxidative mitochondrial metabolism, to take advantage of the abundant fibroblast fuel supply. This simple model of "metabolic-symbiosis" has now been independently validated in several different types of human cancers, including breast, ovarian, and prostate tumors. Biomarkers of metabolic-symbiosis are excellent predictors of tumor recurrence, metastasis, and drug resistance, as well as poor patient survival. New pre-clinical models of metabolic-symbiosis have been generated and they genetically validate …

Circulating Tumor Dna To Monitor Metastatic Breast Cancer., Massimo Cristofanilli, Paolo Fortina

Kimmel Cancer Center Faculty Papers

No abstract provided.

Altered Drainage Patterns In Patients With Melanoma And Previous Axillary Dissection., Caitlyn M. Johnson, Charles Intenzo, Michael Mastrangelo, Kendra Feeney, Adam C. Berger

Department of Surgery Faculty Papers

The incidence of melanoma is increasing rapidly in the United States. Sentinel lymph node biopsy is an important diagnostic tool in the treatment and staging of melanoma. However, many patients with melanoma will have had lymph node surgery for previous melanoma or breast cancer. We set out to examine alterations in drainage patterns in patients with previous axillary dissection for breast cancer. We reviewed four patients with truncal and/or extremity melanomas and examined their lymphoscintigraphy and drainage patterns. Three patients with truncal melanoma mapped to cervical lymph nodes and a fourth patient with an arm melanoma mapped to her previously …

Caloric Restriction Augments Radiation Efficacy In Breast Cancer., Anthony D Saleh, Brittany A Simone, Juan Palazzo, Jason E Savage, Yuri Sano, Tu Dan, Lianjin Jin, Colin E Champ, Shuping Zhao, Meng Lim, Frederica Sotgia, Kevin Camphausen, Richard G Pestell, James B Mitchell, Michael P Lisanti, Nicole L Simone

Kimmel Cancer Center Faculty Papers

Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories …

Breast Cancer Antiestrogen Resistance 3 (Bcar3) Promotes Cell Motility By Regulating Actin Cytoskeletal And Adhesion Remodeling In Invasive Breast Cancer Cells., Ashley L Wilson, Randy S Schrecengost, Michael S Guerrero, Keena S Thomas, Amy H Bouton

Department of Cancer Biology Faculty Papers

Metastatic breast cancer is incurable. In order to improve patient survival, it is critical to develop a better understanding of the molecular mechanisms that regulate metastasis and the underlying process of cell motility. Here, we focus on the role of the adaptor molecule Breast Cancer Antiestrogen Resistance 3 (BCAR3) in cellular processes that contribute to cell motility, including protrusion, adhesion remodeling, and contractility. Previous work from our group showed that elevated BCAR3 protein levels enhance cell migration, while depletion of BCAR3 reduces the migratory and invasive capacities of breast cancer cells. In the current study, we show that BCAR3 is …

Acetylation Of The Cell-Fate Factor Dachshund Determines P53 Binding And Signaling Modules In Breast Cancer., Ke Chen, Kongming Wu, Michael Gormley, Adam Ertel, Jing Wang, Wei Zhang, Jie Zhou, Gabriele Disante, Zhiping Li, Hallgeir Rui, Andrew A Quong, Steven B Mcmahon, Haiteng Deng, Michael P Lisanti, Chenguang Wang, Richard G Pestell

Department of Cancer Biology Faculty Papers

Breast cancer is a leading form of cancer in the world. The Drosophila Dac gene was cloned as an inhibitor of the hyperactive epidermal growth factor (EGFR), ellipse. Herein, endogenous DACH1 co-localized with p53 in a nuclear, extranucleolar compartment and bound to p53 in human breast cancer cell lines, p53 and DACH1 bound common genes in Chip-Seq. Full inhibition of breast cancer contact-independent growth by DACH1 required p53. The p53 breast cancer mutants R248Q and R273H, evaded DACH1 binding. DACH1 phosphorylation at serine residue (S439) inhibited p53 binding and phosphorylation at p53 amino-terminal sites (S15, S20) enhanced DACH1 binding. DACH1 …

Peripheral T-Cell Lymphomas: A Review Of Current Approaches And Hopes For The Future., Alan P Skarbnik, Meher Burki, Barbara Pro

Kimmel Cancer Center Faculty Papers

Peripheral T-cell lymphomas (PTCL) are a diverse group of lymphoproliferative disorders, which share a common denominator of overall poor prognosis, with few exceptions. In this article, the authors review current standard of care approaches for the treatment of PTCLs, the role of stem-cell/bone marrow transplantation, and current developments in novel targeted therapies.

Bortezomib (Ps-341) Treatment Decreases Inflammation And Partially Rescues The Expression Of The Dystrophin-Glycoprotein Complex In Grmd Dogs., Karla P C Araujo, Gloria Bonuccelli, Caio N Duarte, Thais P Gaiad, Dayson F Moreira, David Feder, José E Belizario, Maria A Miglino, Michael P Lisanti, Carlos E Ambrosio

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Golden retriever muscular dystrophy (GRMD) is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD) in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC) via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs) with the proteasome inhibitor bortezomib, and three were control dogs (CD). Dogs were treated with bortezomib using the same treatment regimen used for multiple myeloma. Pharmacodynamics were evaluated by measuring the inhibition of 20S proteasome activity …

The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum

Department of Cancer Biology Faculty Papers

Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 …

The Ccl5/Ccr5 Axis Promotes Metastasis In Basal Breast Cancer., Marco Velasco-Velázquez, Richard G Pestell

Kimmel Cancer Center Faculty Papers

Recently, we have shown that the CCL5/CCR5 axis is active in patients affected by an aggressive basal subtype of breast cancer. Using preclinical models, we have demonstrated that CCR5 promotes breast cancer invasiveness and metastatic potential, while CCR5 inhibition abrogates them. Thus, CCR5 antagonists may constitute an alternative therapeutic approach for patients affected by metastatic basal breast cancer.

Optimizing Parametrial Aperture Design Utilizing Hdr Brachytherapy Isodose Distribution., Katherine L Chapman, Nitin Ohri, Timothy N Showalter, Laura A Doyle

Department of Radiation Oncology Faculty Papers

Treatment of cervical cancer includes combination of external beam radiation therapy (EBRT) and brachytherapy (BRT). Traditionally, coronal images displaying dose distribution from a ring and tandem (R&T) implant aid in construction of parametrial boost fields. This research aimed to evaluate a method of shaping parametrial fields utilizing contours created from the high-dose-rate (HDR) BRT dose distribution. Eleven patients receiving HDR-BRT via R&T were identified. The BRT and EBRT CT scans were sent to FocalSim (v4.62)(®) and fused based on bony anatomy. The contour of the HDR isodose line was transferred to the EBRT scan. The EBRT scan was sent to …

Roles And Mechanism Of Mir-199a And Mir-125b In Tumor Angiogenesis., Jun He, Yi Jing, Wei Li, Xu Qian, Qing Xu, Feng-Shan Li, Ling-Zhi Liu, Bing-Hua Jiang, Yue Jiang

Computational Medicine Center Faculty Papers

MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. Moreover, the levels of miR-199a and miR-125b were negatively correlated with VEGF mRNA levels in ovarian tissues. We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and …

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation With Optimized T-Cell Dosing: Early Immune Reconstitution Leads To Better Outcomes, Sameh Gaballa, Onder Alpdogan, Matthew Carabasi, Joanne Filicko, Margaret Kasner, Ubaldo E. Martinez-Outshoorn, Md, John L Wagner, Mark Weiss, Neal Flomenberg, Delores Grosso

Department of Medical Oncology Faculty Papers

We developed a 2-step approach to myeloablative haploidentical HSCT in which patients receive a large fixed dose of cyclophosphamide (CY)-tolerized T cells separately frm the HSC infusion in the hopes of accelerating post HSCT immune reconstitution (IR). The uniformity of the T cell dosing facilitates comparison of patients without (low risk) and with (high risk) active malignancy at HSCT to ascertain the impact of disease status at HSCT on IR with fewer confounding effects from conditioning or T cell dosing.

Early Results Of Prostate Cancer Radiation Therapy: An Analysis With Emphasis On Research Strategies To Improve Treatment Delivery And Outcomes., Kosj Yamoah, Kwamena Beecham, Sarah E Hegarty, Terry Hyslop, Timothy Showalter, Joel Yarney

Department of Radiation Oncology Faculty Papers

ABSTRACT: BACKGROUND: There is scant data regarding disease presentation and treatment response among black men living in Africa. In this study we evaluate disease presentation and early clinical outcomes among Ghanaian men with prostate cancer treated with external beam radiotherapy (EBRT). METHODS: A total of 379 men with prostate cancer were referred to the National Center for Radiotherapy, Ghana from 2003 to 2009. Data were collected regarding patient-and tumor-related factors such as age, prostate specific antigen (PSA), Gleason score (GS), clinical stage (T), and use of androgen deprivation therapy (ADT). For patients who received EBRT, freedom from biochemical failure (FFbF) …

Dynamic Recruitment Of Micrornas To Their Mrna Targets In The Regenerating Liver., Jonathan Schug, Lindsay B Mckenna, Gabriel Walton, Nicholas Hand, Sarmistha Mukherjee, Kow Essuman, Zhongjie Shi, Yan Gao, Karen Markley, Momo Nakagawa, Vasumathi Kameswaran, Anastassios Vourekas, Joshua R Friedman, Klaus H Kaestner, Linda E Greenbaum

Department of Cancer Biology Faculty Papers

BACKGROUND: Validation of physiologic miRNA targets has been met with significant challenges. We employed HITS-CLIP to identify which miRNAs participate in liver regeneration, and to identify their target mRNAs.

RESULTS: miRNA recruitment to the RISC is highly dynamic, changing more than five-fold for several miRNAs. miRNA recruitment to the RISC did not correlate with changes in overall miRNA expression for these dynamically recruited miRNAs, emphasizing the necessity to determine miRNA recruitment to the RISC in order to fully assess the impact of miRNA regulation. We incorporated RNA-seq quantification of total mRNA to identify expression-weighted Ago footprints, and developed a microRNA …

Dual Fluorescent Molecular Substrates Selectively Report The Activation, Sustainability And Reversibility Of Cellular Pkb/Akt Activity., Duanwen Shen, Mingfeng Bai, Rui Tang, Baogang Xu, Xiaoming Ju, Richard Pestell, Samuel Achilefu

Department of Cancer Biology Faculty Papers

Using a newly developed near-infrared (NIR) dye that fluoresces at two different wavelengths (dichromic fluorescence, DCF), we discovered a new fluorescent substrate for Akt, also known as protein kinase B, and a method to quantitatively report this enzyme's activity in real time. Upon insulin activation of cellular Akt, the enzyme multi-phosphorylated a single serine residue of a diserine DCF substrate in a time-dependent manner, culminating in monophospho- to triphospho-serine products. The NIR DCF probe was highly selective for the Akt1 isoform, which was demonstrated using Akt1 knockout cells derived from MMTV-ErbB2 transgenic mice. The DCF mechanism provides unparalleled potential to …

Gender Differences In Attitudes Impeding Colorectal Cancer Screening., Paul Ritvo, Ronald E. Myers, Lawrence Paszat, Mardie Serenity, Daniel F Perez, Linda Rabeneck

Department of Medical Oncology Faculty Papers

BACKGROUND: Colorectal cancer screening (CRCS) is the only type of cancer screening where both genders reduce risks by similar proportions with identical procedures. It is an important context for examining gender differences in disease-prevention, as CRCS significantly reduces mortality via early detection and prevention. In efforts to increase screening adherence, there is increasing acknowledgment that obstructive attitudes prevent CRCS uptake. Precise identification of the gender differences in obstructive attitudes is necessary to improve uptake promotion. This study randomly sampled unscreened, screening - eligible individuals in Ontario, employing semi-structured interviews to elicit key differences in attitudinal obstructions towards colorectal cancer screening …

Presence Of Anaplastic Lymphoma Kinase In Inflammatory Breast Cancer., Fredika M Robertson, Emanuel F Petricoin Iii, Steven J Van Laere, Francois Bertucci, Khoi Chu, Sandra V Fernandez, Zhaomei Mu, Katherine Alpaugh, Jianming Pei, Rita Circo, Julia Wulfkuhle, Zaiming Ye, Kimberly M Boley, Hui Liu, Ricardo Moraes, Xuejun Zhang, Ruggero Demaria, Sanford H Barsky, Guoxian Sun, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

Although Inflammatory Breast Cancer (IBC) is recognized as the most metastatic variant of locally advanced breast cancer, the molecular basis for the distinct clinical presentation and accelerated program of metastasis of IBC is unknown. Reverse phase protein arrays revealed activation of the receptor tyrosine kinase, anaplastic lymphoma kinase (ALK) and biochemically-linked downstream signaling molecules including JAK1/STAT3, AKT, mTor, PDK1, and AMPKβ in pre-clinical models of IBC. To evaluate the clinical relevance of ALK in IBC, analysis of 25 IBC patient tumors using the FDA approved diagnostic test for ALK genetic abnormalities was performed. These studies revealed that 20/25 (80%) had …