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Articles 13051 - 13080 of 14287

Full-Text Articles in Medical Specialties

Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar Jan 2013

Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.

Methods

Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled …


Autoclaved Tumor Bone For Skeletal Reconstruction In Paediatric Patients: A Low Cost Alternative In Developing Countries, Masood Umer, Hafiz Muhammad Umer, Irfan Qadir, Haroon Rashid, Rabia Awan, Raza Askari, Shamvil Ashraf Jan 2013

Autoclaved Tumor Bone For Skeletal Reconstruction In Paediatric Patients: A Low Cost Alternative In Developing Countries, Masood Umer, Hafiz Muhammad Umer, Irfan Qadir, Haroon Rashid, Rabia Awan, Raza Askari, Shamvil Ashraf

Section of Orthopaedic Surgery

We reviewed in this series forty patients of pediatric age who underwent resection for malignant tumors of musculoskeletal system followed by biological reconstruction. Our surgical procedure for reconstruction included (1) wide en bloc resection of the tumor; (2) curettage of tumor from the resected bone; (3) autoclaving for 8 minutes (4) bone grafting from the fibula (both vascularized and nonvascularized fibular grafts used); (5) reimplantation of the autoclaved bone into the host bone defect and fixation with plates. Functional evaluation was done using MSTS scoring system. At final followup of at least 18 months (mean 29.2 months), 31 patients had …


Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad Jan 2013

Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

HMLEs (HMLE-SNAIL and Kras-HMLE, Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We had earlier developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using systems biology and pathway network analysis, we show that GN-25 could cause reversal of EMT leading to mesenchymal-to-epithelial transition (MET) in a well-recognized HMLE-SNAIL and Kras-HMLE-SNAIL models.

Results

GN-25 induced MET was found to be consistent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. Pathway network analysis of mRNA expression …


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 Jan 2013

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 Jan 2013

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 …


Redox-Regulated Relb-Ar Axis Mediates Prostate Specific Antigen Expression: Insight In Prostate Cancer Response To Radiation Therapy, Lu Miao Jan 2013

Redox-Regulated Relb-Ar Axis Mediates Prostate Specific Antigen Expression: Insight In Prostate Cancer Response To Radiation Therapy, Lu Miao

Theses and Dissertations--Toxicology and Cancer Biology

Although the prostate specific antigen (PSA) test is widely used in clinical settings for prostate cancer (PCa) diagnosis and post-treatment follow-up monitoring, false positive PSA test results, which contribute to over-diagnosis of PCa, and false negative results, which miss some patients with aggressive PCa, remain problems of clinical importance.

Our study demonstrates that radiation therapy, which is widely used for treatment of localized PCa, generates TNF-α in tumor cells and stromal fibroblasts, redox dependently. Interestingly, TNF-α rapidly and transiently triggers the RelA-mediated NF-κB canonical pathway, but its effect on RelB expression is more robust and long lasting, which leads to …


Oncolog, Volume 58, Number 01, January 2013, Joe Munch, Sunni Hosemann Jan 2013

Oncolog, Volume 58, Number 01, January 2013, Joe Munch, Sunni Hosemann

OncoLog MD Anderson's Report to Physicians (All issues) Archives

  • Emerging Vaccines Take Aim at Preventing Recurrent Breast Cancer: Myriad advances have been made in the treatment of breast cancer, and cures are achieved in many patients. However, there are still patients whose cancer recurs, and most of these patients will die of their disease. This indicates a need for other therapies that can be used to prevent recurrent disease. One potential option is breast cancer vaccines.
  • Compass: Hepatocellular Carcinoma: Concomitant liver disease affects treatment options
  • HOUSE CALL: Music Therapy-Music therapists help cancer patients manage stress and side effects


Targeting And Killing Of Glioblastoma With Activated T Cells Armed With Bispecific Antibodies, Ian M. Zitron, Archana Thakur, Oxana Norkina, Geoffrey R. Barger, Lawrence G. Lum, Sandeep Mittal Jan 2013

Targeting And Killing Of Glioblastoma With Activated T Cells Armed With Bispecific Antibodies, Ian M. Zitron, Archana Thakur, Oxana Norkina, Geoffrey R. Barger, Lawrence G. Lum, Sandeep Mittal

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2.

Methods

ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines.

Results

EGFRBi-armed ATC killed up to 85% of U87, …


Initial Results Tracking Patient Satisfaction In An Oncology Navigation Program, Dorothy Morrone Rnc, Ms, Ocn, Diane Mchugh Bsn, Ocn, Cbpn-Ic, Laura Beaupre Bsn, Ocn, Cbpn-Ic, Kathy Sevedge Rn, Ma, Aocn, Jane Zubia Rn, Ocn, Cbpn I-C, Raizalie Roman-Rosado Bsn, Ocn, Cmsrn, Martiza Y. Chicas Rn, Pccn Jan 2013

Initial Results Tracking Patient Satisfaction In An Oncology Navigation Program, Dorothy Morrone Rnc, Ms, Ocn, Diane Mchugh Bsn, Ocn, Cbpn-Ic, Laura Beaupre Bsn, Ocn, Cbpn-Ic, Kathy Sevedge Rn, Ma, Aocn, Jane Zubia Rn, Ocn, Cbpn I-C, Raizalie Roman-Rosado Bsn, Ocn, Cmsrn, Martiza Y. Chicas Rn, Pccn

Patient Care Services / Nursing

No abstract provided.


Tyrosinase Reactive T Cells Reject Or Edit Established Human Melanomas In Vivo, Telma Raquela Martins Da Palma Jan 2013

Tyrosinase Reactive T Cells Reject Or Edit Established Human Melanomas In Vivo, Telma Raquela Martins Da Palma

MUSC Theses and Dissertations

Adoptive transfer of T cell receptor (TCR) gene transduced T cells can mediate dramatic tumor regressions in melanoma patients. However, improvements in these therapies are needed as most patients either fail to respond to the therapy or eventually experience recurrent disease. To evaluate the therapeutic potential of T cells expressing the high-affinity TIL 1383I TCR for treatment of human melanomas, we developed xenograft models for the malignancy. Human T cells transduced with the TIL 1383I TCR exhibited strong in vitro reactivity against HLA-A2+Tyrosinase+ targets but failed to impact tumor growth in vivo. In contrast, TIL 1383I TCR-expressing murine T cells …


Acid Ceramidase Promotes Akt Activation And Nuclear Export Of Pten Through S1p Signaling, Thomas Hendrix Beckham Jan 2013

Acid Ceramidase Promotes Akt Activation And Nuclear Export Of Pten Through S1p Signaling, Thomas Hendrix Beckham

MUSC Theses and Dissertations

Prostate cancer is a leading cause of cancer and cancer-related mortality in males in the United States. Acid ceramidase is frequently overexpressed in prostate cancer and catalyzes the deacylation of proapoptotic ceramide into sphingosine. Sphingosine is converted by sphingosine kinases into sphingosine 1-phosphate, which promotes numerous pro-cancer phenotypes. Due to the frequent overexpression of acid ceramidase in prostate cancer and its net cancer promoting signaling effects achieved by reducing ceramide and generating sphingosine 1-phosphate, the impact of acid ceramidase, and the lipid profiles it alters, on prostate cancer cell signaling were studied. Here we report the activation of the oncogeneic …


Vascular Endothelial Growth Factor (Vegf) Expression In Locally Advanced Prostate Cancer: Secondary Analysis Of Radiation Therapy Oncology Group (Rtog) 8610., Larry Pan, Seunghee Baek, Pamela R Edmonds, Mack Roach, Harvey Wolkov, Satish Shah, Alan Pollack, M Elizabeth Hammond, Adam P Dicker Jan 2013

Vascular Endothelial Growth Factor (Vegf) Expression In Locally Advanced Prostate Cancer: Secondary Analysis Of Radiation Therapy Oncology Group (Rtog) 8610., Larry Pan, Seunghee Baek, Pamela R Edmonds, Mack Roach, Harvey Wolkov, Satish Shah, Alan Pollack, M Elizabeth Hammond, Adam P Dicker

Department of Radiation Oncology Faculty Papers

BACKGROUND: Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer.

METHODS: The analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from …


Systematic Review Of Research Into The Psychological Aspects Of Prostate Cancer In Asia: What Do We Know?, Suzanne Kathleen Chambers, Melissa Karen Hyde, David Fu-Keung Ip, Jeffrey Charles Dunn, Robert Alexander Gardiner Jan 2013

Systematic Review Of Research Into The Psychological Aspects Of Prostate Cancer In Asia: What Do We Know?, Suzanne Kathleen Chambers, Melissa Karen Hyde, David Fu-Keung Ip, Jeffrey Charles Dunn, Robert Alexander Gardiner

Research outputs 2013

Background: To review the peer reviewed literature on the psychological aspects of the prostate cancer experience of men in Asia.

Materials and Methods: Medline and PsycINFO, CINAHL, ProQuest, and Web of Science (1999 – November Week 4, 2012) were searched. Inclusion criteria were: included men with prostate cancer and/or their partners or caregivers who identify as Asian recruited in an Asian country; and assessed health-related quality of life, psychological and social adjustment relating to prostate cancer and published in English after 1st January 1999 and prior to 30th November, 2012.

Study aims: design; quality; level of evidence, and key results …


Health-Related Quality Of Life And Life Satisfaction In Colorectal Cancer Survivors: Trajectories Of Adjustment, Jeff Dunn, Shu Kay Ng, William Breitbart, Joanne Aitken, Pip Youl, Peter D. Baade, Suzanne K. Chambers Jan 2013

Health-Related Quality Of Life And Life Satisfaction In Colorectal Cancer Survivors: Trajectories Of Adjustment, Jeff Dunn, Shu Kay Ng, William Breitbart, Joanne Aitken, Pip Youl, Peter D. Baade, Suzanne K. Chambers

Research outputs 2013

Background: This longitudinal study describes the five year trajectories of health-related quality of life (HR-QOL) and life satisfaction in long term colorectal cancer survivors.Patients and methods: A population-based sample of 1966 colorectal cancer survivors were surveyed at six time points from five months to five years post-diagnosis. Predictor variables were: socio-demographic variables, optimism; cancer threat appraisal; perceived social support. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Colorectal (HR-QOL); and the Satisfaction with Life Scale. Growth mixture models were applied to identify trajectory classes and their predictors.Results: Distinct adjustment trajectories were identified for HR-QOL and life satisfaction. …


Does The Addition Of Muramyl Tripeptide To Chemotherapy Improve Overall Survival For Patients With Osteosarcoma?, Jennifer Jones Jan 2013

Does The Addition Of Muramyl Tripeptide To Chemotherapy Improve Overall Survival For Patients With Osteosarcoma?, Jennifer Jones

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the addition of muramyl tripeptide to chemotherapy improve overall survival for patients with osteosarcoma?”

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2005 and 2009.

DATA SOURCES: Randomized controlled trials evaluating the addition of muramyl tripeptide (MTP) to chemotherapy for patients with osteosarcoma were found using Medline/PubMed databases.

OUTCOMES MEASURED: Event-free survival (EFS) and overall survival were the outcome measures used to determine the effectiveness of the additional chemotherapy treatment in osteosarcoma patients. EFS was defined as …


Is Fentanyl Pectin Nasal Spray Safe And Effective For Patients With Breakthrough Cancer Pain?, Salina G. Elengical Jan 2013

Is Fentanyl Pectin Nasal Spray Safe And Effective For Patients With Breakthrough Cancer Pain?, Salina G. Elengical

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether fentanyl pectin nasal spray (FPNS) is safe and effective treatment for patients with breakthrough cancer pain.

STUDY DESIGN: Review of three English language primary randomized controlled trials published 2010-2011.

DATA SOURCES: Multicenter, randomized, double-blind, double-dummy, placebo-controlled trials comparing fentanyl pectin nasal spray, immediate-release morphine sulfate, and/or nasal spray placebo were found using PubMed, COCHRANE, and Medline databases.

OUTCOME MEASURED: All three studies essentially used similar parameters to measure effectiveness and safety of fentanyl pectin nasal spray compared to oral immediate-release morphine sulfate and/or placebo. Baseline pain intensity …


Expression And Regulation Of Map Kinase Phosphatases 1 And 2 In Breast Cancer Tamoxifen Sensitivity, Kelly Haagenson Jan 2013

Expression And Regulation Of Map Kinase Phosphatases 1 And 2 In Breast Cancer Tamoxifen Sensitivity, Kelly Haagenson

Wayne State University Dissertations

ABSTRACT

EXPRESSION AND REGULATION OF MAP KINASE PHOSPHATASES 1 and 2 IN BREAST CANCER TAMOXIFEN SENSITIVITY

by

KELLY K. HAAGENSON

May 2013

Advisor: Dr. Malathy Shekhar

Co-Advisor: Dr. Gen Sheng Wu

Major: Cancer Biology

Degree: Doctor of Philosophy

The deregulation of cell signaling is a very important component in the development and progression of cancer. One group of signaling molecules that has been implicated in these processes is the Mitogen-Activated Protein Kinase (MAPK) family which consists of three major branches in mammalian cells: ERK, JNK and p38. The activity of these kinases has wide-ranging effects within the cell and must …


Analysis Of The Structure And Function Of A Timp-1/Cd63 Complex And Its Relationship To An Mt1-Mmp/Cd63 Complex, Richard B. Warner Jan 2013

Analysis Of The Structure And Function Of A Timp-1/Cd63 Complex And Its Relationship To An Mt1-Mmp/Cd63 Complex, Richard B. Warner

Wayne State University Dissertations

The relationship of the extra-cellular matrix (ECM) and secreted proteins to intra-cellular functions has an important impact on disease progression. The tissue inhibitors of metalloproteinases (TIMPs), of which there are four, are known for their broad metalloprotease inhibitory abilities. TIMP-1 has been widely studied as an inhibitor of matrix metalloproteinases (MMPs) and therefore as a molecule that prevents ECM degradation and proteolytic cleavage of extra-cellular molecules, processes thought to be critical for tumor invasion and metastasis. However, TIMP-1 has shown in the clinic to have increased expression in cases of disease progression; especially, it is associated with poor prognosis in …


Cost Effective Improvement In The Protocol For Detection Of Haemoglobin Variants –A Step Forward In Quality Assurance, Natasha Ali, Mohammad Khurshid Jan 2013

Cost Effective Improvement In The Protocol For Detection Of Haemoglobin Variants –A Step Forward In Quality Assurance, Natasha Ali, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Background: We report the results of a cost effective improvement in the protocol for detection of haemoglobin variants which incorporates the findings of peripheral blood film along with the results of HPLC.
Findings: A total of n = 10,844 samples were received from January 2011 till August 2011. Diagnosis of haemoglobinopathy was made in n = 1123 samples while other abnormalities included iron deficiency anaemia, megaloblastic anaemia, malarial parasite, autoimmune haemolytic anaemia and G6PD deficiency (n = 2473).
Conclusion: We diagnosed 23% of abnormalities other than haemoglobinopathy by reviewing peripheral smear of samples received for detection of …


Frequency And Outcome Of Graft Versus Host Disease After Stem Cell Transplantation: A Six-Year Experience From A Tertiary Care Center In Pakistan, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh, Nehal Masood Jan 2013

Frequency And Outcome Of Graft Versus Host Disease After Stem Cell Transplantation: A Six-Year Experience From A Tertiary Care Center In Pakistan, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh, Nehal Masood

Department of Pathology and Laboratory Medicine

Objective: The objective of this study was to evaluate the frequency and outcome of graft versus host disease after stem cell transplantation for various haematological disorders in Pakistan.
Materials and Methods: Pretransplant workup of the patient and donor was performed. Mobilization was done with G-CSF 300 mu g twice daily for five day. Standard GvHD prophylaxis was done with methotrexate 15mg/m(2) on day +1 followed by 10mg/m(2) on days +3 and +6 and cyclosporine. Grading was done according to the Glucksberg classification.
Results: A total of 153 transplants were done from April 2004 to December 2011. Out of these were …


Glutamine Supplementation Alleviates Vasculopathy And Corrects Metabolic Profile In An In Vivo Model Of Endothelial Cell Dysfunction., Francesco Addabbo, Qiuying Chen, Dhara P Patel, May Rabadi, Brian Ratliff, Frank Zhang, Jean-Francois Jasmin, Michael Wolin, Michael Lisanti, Steven S Gross, Michael S Goligorsky Jan 2013

Glutamine Supplementation Alleviates Vasculopathy And Corrects Metabolic Profile In An In Vivo Model Of Endothelial Cell Dysfunction., Francesco Addabbo, Qiuying Chen, Dhara P Patel, May Rabadi, Brian Ratliff, Frank Zhang, Jean-Francois Jasmin, Michael Wolin, Michael Lisanti, Steven S Gross, Michael S Goligorsky

Kimmel Cancer Center Faculty Papers

Endothelial Cell Dysfunction (ECD) is a recognized harbinger of a host of chronic cardiovascular diseases. Using a mouse model of ECD triggered by treatment with L-Nω-methylarginine (L-NMMA), we previously demonstrated that renal microvasculature displays a perturbed protein profile, including diminished expression of two key enzymes of the Krebs cycle associated with a Warburg-type suppression of mitochondrial metabolism. We hypothesized that supplementation with L-glutamine (GLN), that can enter the Krebs cycle downstream this enzymatic bottleneck, would normalize vascular function and alleviate mitochondrial dysfunction. To test this hypothesis, mice with chronic L-NMMA-induced ECD were co-treated with GLN at different concentrations for 2 …


A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp Jan 2013

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …


Doxorubicin-Induced, Tnf-Α-Mediated Brain Oxidative Stress, Neurochemical Alterations, And Cognitive Decline: Insights Into Mechanisms Of Chemotherapy Induced Cognitive Impairment And Its Prevention, Jeriel T. Keeney Jan 2013

Doxorubicin-Induced, Tnf-Α-Mediated Brain Oxidative Stress, Neurochemical Alterations, And Cognitive Decline: Insights Into Mechanisms Of Chemotherapy Induced Cognitive Impairment And Its Prevention, Jeriel T. Keeney

Theses and Dissertations--Chemistry

The works presented in this dissertation provide insights into the mechanisms of chemotherapy-induced cognitive impairment (CICI or “ChemoBrain”) and take steps toward outlining a preventive strategy. CICI is now widely recognized as a complication of cancer chemotherapy experienced by a large percentage of cancer survivors. Approximately fifty percent of existing FDA-approved anti-cancer drugs generate reactive oxygen species (ROS). Doxorubicin (Dox), a prototypical ROS-generating chemotherapeutic agent, produces the reactive superoxide radical anion (O2-•) in vivo. Dox treatment results in oxidation of plasma proteins, including ApoA-I, leading to TNF-α-mediated oxidative stress in plasma and brain. TNF-α elevation in brain …


Gender Differences In Attitudes Impeding Colorectal Cancer Screening., Paul Ritvo, Ronald E. Myers, Lawrence Paszat, Mardie Serenity, Daniel F Perez, Linda Rabeneck Jan 2013

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 Jan 2013

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 …


Dysregulated Methylation At Imprinted Genes In Prostate Tumor Tissue Detected By Methylation Microarray., Daniel I Jacobs, Yingying Mao, Alan Fu, William Kevin Kelly, Yong Zhu Jan 2013

Dysregulated Methylation At Imprinted Genes In Prostate Tumor Tissue Detected By Methylation Microarray., Daniel I Jacobs, Yingying Mao, Alan Fu, William Kevin Kelly, Yong Zhu

Department of Medical Oncology Faculty Papers

BACKGROUND: Imprinting is an important epigenetic regulator of gene expression that is often disrupted in cancer. While loss of imprinting (LOI) has been reported for two genes in prostate cancer (IGF2 and TFPI2), disease-related changes in methylation across all imprinted gene regions has not been investigated.

METHODS: Using an Illumina Infinium Methylation Assay, we analyzed methylation of 396 CpG sites in the promoter regions of 56 genes in a pooled sample of 12 pairs of prostate tumor and adjacent normal tissue. Selected LOI identified from the array was validated using the Sequenom EpiTYPER assay for individual samples and further confirmed …


Ezh2 Knockdown Suppresses The Growth And Invasion Of Human Inflammatory Breast Cancer Cells., Zhaomei Mu, Hua Li, Sandra V Fernandez, Katherine R Alpaugh, Rugang Zhang, Massimo Cristofanilli Jan 2013

Ezh2 Knockdown Suppresses The Growth And Invasion Of Human Inflammatory Breast Cancer Cells., Zhaomei Mu, Hua Li, Sandra V Fernandez, Katherine R Alpaugh, Rugang Zhang, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Inflammatory breast cancer (IBC) is the most metastatic variant of breast cancer with the poorest survival in all types of breast cancer patients and presently therapeutic targets for IBC are very limited. Enhancer of zeste homolog 2 (EZH2) is frequently expressed in human IBC and its expression positively correlates with worse clinical outcome. However, the molecular basis for EZH2 promoting IBC has not been explored. Here, we investigated the functional role of EZH2 in IBC cells by examining the effects of its knockdown on the formation of tumor spheroids and invasion of these cells in vitro and in vivo …


Associations Among Family History Of Cancer, Cancer Screening And Lifestyle Behaviors: A Population-Based Study, Georgiana Bostean, Catherine M. Crespi, William J. Mccarthy Jan 2013

Associations Among Family History Of Cancer, Cancer Screening And Lifestyle Behaviors: A Population-Based Study, Georgiana Bostean, Catherine M. Crespi, William J. Mccarthy

Sociology Faculty Articles and Research

Purpose Some cancers are largely preventable through modification of certain behavioral risk factors and preventive screening, even among those with a family history of cancer. This study examined the associations between (1) family cancer history and cancer screening, (2) family history and cancer preventive lifestyle behaviors, and (3) cancer screening and lifestyle behaviors.

Methods Data were from the 2009 California Health Interview Survey (n = 12,603). Outcomes included screening for breast cancer (BC) and colorectal cancer (CRC) and six cancer preventive lifestyle behaviors, based on World Cancer Research Fund recommendations. Multivariate logistic regression analyses, stratified by gender and race–ethnicity, examined …


Late Developing Mammary Tumors And Hyperplasia Induced By A Low-Oncogenic Variant Of Mouse Mammary Tumor Virus (Mmtv) Express Genes Identical To Those Induced By Canonical Mmtv, Robert D. Bruno Jan 2013

Late Developing Mammary Tumors And Hyperplasia Induced By A Low-Oncogenic Variant Of Mouse Mammary Tumor Virus (Mmtv) Express Genes Identical To Those Induced By Canonical Mmtv, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Publications

Background: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.

Findings: We confirmed the presence of …


Novel T(5;19) Translocation In A Patient With Pdgfrb Associated Chronic Leukemia: Implications For Treatment Strategy., Joel D Provenzano, J Phillip Kuebler Jan 2013

Novel T(5;19) Translocation In A Patient With Pdgfrb Associated Chronic Leukemia: Implications For Treatment Strategy., Joel D Provenzano, J Phillip Kuebler

Oncology Articles

Myeloproliferative disorders are variable disorders, based on the genetic abnormality present and the cell line progenitors that are affected. In this case, we discuss a novel gene translocation in the subset of PDGFRB mutations, first seen with prominent hyperbasophilia. This case demonstrates the possibility for lower therapeutic doses of imatinib mesylate than previously reported, in order to control leukocyte counts and reverse the genetic mutation.