Medicine and Health Sciences Commons^™

Classification Of Current Anticancer Immunotherapies., Lorenzo Galluzzi, Erika Vacchelli, José-Manuel Bravo-San Pedro, Aitziber Buqué, Laura Senovilla, Elisa Elena Baracco, Norma Bloy, Francesca Castoldi, Jean-Pierre Abastado, Patrizia Agostinis, Ron N Apte, Fernando Aranda, Maha Ayyoub, Philipp Beckhove, Jean-Yves Blay, Laura Bracci, Anne Caignard, Chiara Castelli, Federica Cavallo, Estaban Celis, Vincenzo Cerundolo, Aled Clayton, Mario P Colombo, Lisa Coussens, Madhav V Dhodapkar, Alexander M Eggermont, Douglas T Fearon, Wolf H Fridman, Jitka Fučíková, Dmitry I Gabrilovich, Jérôme Galon, Abhishek Garg, François Ghiringhelli, Giuseppe Giaccone, Eli Gilboa, Sacha Gnjatic, Axel Hoos, Anne Hosmalin, Dirk Jäger, Pawel Kalinski, Klas Kärre, Oliver Kepp, Rolf Kiessling, John M Kirkwood, Eva Klein, Alexander Knuth, Claire E Lewis, Roland Liblau, Michael T Lotze, Enrico Lugli, Jean-Pierre Mach, Fabrizio Mattei, Domenico Mavilio, Ignacio Melero, Cornelis J Melief, Elizabeth A Mittendorf, Lorenzo Moretta, Adekunke Odunsi, Hideho Okada, Anna Karolina Palucka, Marcus E Peter, Kenneth J Pienta, Angel Porgador, George C Prendergast, Gabriel A Rabinovich, Nicholas P Restifo, Naiyer Rizvi, Catherine Sautès-Fridman, Hans Schreiber, Barbara Seliger, Hiroshi Shiku, Bruno Silva-Santos, Mark J Smyth, Daniel E Speiser, Radek Spisek, Pramod K Srivastava, James E Talmadge, Eric Tartour, Sjoerd H Van Der Burg, Benoît J Van Den Eynde, Richard Vile, Hermann Wagner, Jeffrey S Weber, Theresa L Whiteside, Jedd D Wolchok, Laurence Zitvogel, Weiping Zou, Guido Kroemer

Kimmel Cancer Center Faculty Papers

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification …

Suppression Of Invasion And Metastasis Of Triple-Negative Breast Cancer Lines By Pharmacological Or Genetic Inhibition Of Slug Activity., Giovanna Ferrari-Amorotti, Claudia Chiodoni, Fei Shen, Sara Cattelani, Angela Rachele Soliera, Gloria Manzotti, Giulia Grisendi, Massimo Dominici, Francesco Rivasi, Mario Paolo Colombo, Alessandro Fatatis, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Most triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic …

Hyperthermia, Radiation And Chemotherapy: The Role Of Heat In Multidisciplinary Cancer Care., Mark Hurwitz, Md, Paul R. Stauffer

Department of Radiation Oncology Faculty Papers

The compelling biologic basis for combining hyperthermia with modern cancer therapies including radiation and chemotherapy was first appreciated nearly half a century ago. Hyperthermia complements radiation as conditions contributing to radio-resistance generally enhance sensitivity to heat and sensitizing effects occur through increased perfusion/tumor oxygenation and alteration of cellular death pathways. Chemosensitization with hyperthermia is dependent on the particular mechanism of effect for each agent with synergistic effects noted for several commonly used agents. Clinically, randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in treatment of a wide range of malignancies. Improvements in …

The Long Non-Coding Rna Pcat-1 Promotes Prostate Cancer Cell Proliferation Through Cmyc., John R. Prensner, Wei Chen, Sumin Han, Matthew K. Iyer, Qi Cao, Vishal Kothari, Joseph R. Evans, Karen E. Knudsen, Michelle T. Paulsen, Mats Ljungman, Theodore S. Lawrence, Arul M. Chinnaiyan, Felix Y. Feng

Department of Cancer Biology Faculty Papers

Long non-coding RNAs (lncRNAs) represent an emerging layer of cancer biology, contributing to tumor proliferation, invasion, and metastasis. Here, we describe a role for the oncogenic lncRNA PCAT-1 in prostate cancer proliferation through cMyc. We find that PCAT-1-mediated proliferation is dependent on cMyc protein stabilization, and using expression profiling, we observed that cMyc is required for a subset of PCAT-1-induced expression changes. The PCAT-1-cMyc relationship is mediated through the post-transcriptional activity of the MYC 3' untranslated region, and we characterize a role for PCAT-1 in the disruption of MYC-targeting microRNAs. To further elucidate a role for post-transcriptional regulation, we demonstrate …

Camk2n1 Inhibits Prostate Cancer Progression Through Androgen Receptor-Dependent Signaling., Tao Wang, Shuiming Guo, Zhuo Liu, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Xiaming Liu, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Shaohua Xu, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Liping Wang, Kongming Wu, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen

Department of Cancer Biology Faculty Papers

Castration resistance is a major obstacle to hormonal therapy for prostate cancer patients. Although androgen independence of prostate cancer growth is a known contributing factor to endocrine resistance, the mechanism of androgen receptor deregulation in endocrine resistance is still poorly understood. Herein, the CAMK2N1 was shown to contribute to the human prostate cancer cell growth and survival through AR-dependent signaling. Reduced expression of CAMK2N1 was correlated to recurrence-free survival of prostate cancer patients with high levels of AR expression in their tumor. CAMK2N1 and AR signaling form an auto-regulatory negative feedback loop: CAMK2N1 expression was down-regulated by AR activation; while …

The Induction Of The P53 Tumor Suppressor Protein Bridges The Apoptotic And Autophagic Signaling Pathways To Regulate Cell Death In Prostate Cancer Cells., Lymor Ringer, Paul Sirajuddin, Lucas Tricoli, Sarah Waye, Muhammad Umer Choudhry, Erika Parasido, Angiela Sivakumar, Mary Heckler, Aisha Naeem, Iman Abdelgawad, Xuefeng Liu, Adam S Feldman, Richard J Lee, Chin-Lee Wu, Venkata Yenugonda, Bhaskar Kallakury, Anatoly Dritschilo, John Lynch, Richard Schlegel, Olga Rodriguez, Richard Pestell, Maria Laura Avantaggiati, Chris Albanese

Kimmel Cancer Center Faculty Papers

The p53 tumor suppressor protein plays a crucial role in influencing cell fate decisions in response to cellular stress. As p53 elicits cell cycle arrest, senescence or apoptosis, the integrity of the p53 pathway is considered a key determinant of anti-tumor responses. p53 can also promote autophagy, however the role of p53-dependent autophagy in chemosensitivity is poorly understood. VMY-1-103 (VMY), a dansylated analog of purvalanol B, displays rapid and potent anti-tumor activities, however the pathways by which VMY works are not fully defined. Using established prostate cancer cell lines and novel conditionally reprogrammed cells (CRCs) derived from prostate cancer patients; …

Hormone Whodunit: Clues For Solving The Case Of Intratumor Androgen Production., Karen E Knudsen

Department of Cancer Biology Faculty Papers

One of the key mechanisms by which prostate cancer cells evade hormone therapy is through intratumor testosterone production. New evidence points toward androstenedione as a potential precursor of intratumor androgen production and furthers nomination of AKR1C3 as a therapeutic target in advanced disease. Clin Cancer Res; 20(21); 5343-5. ©2014 AACR.

Experimental Study Of Needle-Tissue Interaction Forces: Effect Of Needle Geometries, Insertion Methods And Tissue Characteristics., Shan Jiang, Pan Li, Yan Yu, Jun Liu, Zhiyong Yang

Department of Radiation Oncology Faculty Papers

A thorough understanding of needle-tissue interaction mechanics is necessary to optimize needle design, achieve robotically needle steering, and establish surgical simulation system. It is obvious that the interaction is influenced by numerous variable parameters, which are divided into three categories: needle geometries, insertion methods, and tissue characteristics. A series of experiments are performed to explore the effect of influence factors (material samples n=5 for each factor) on the insertion force. Data were collected from different biological tissues and a special tissue-equivalent phantom with similar mechanical properties, using a 1-DOF mechanical testing system instrumented with a 6-DOF force/torque (F/T) sensor. The …

Gucy2c Lysosomotropic Endocytosis Delivers Immunotoxin Therapy To Metastatic Colorectal Cancer., Glen P Marszalowicz, Adam E. Snook, Michael Sullivan Magee, Dante Merlino, Lisa D Berman-Booty, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The emergence of targeted cancer therapy has been limited by the paucity of determinants which are tumor-specific and generally associated with disease, and have cell dynamics which effectively deploy cytotoxic payloads. Guanylyl cyclase C (GUCY2C) may be ideal for targeting because it is normally expressed only in insulated barrier compartments, including intestine and brain, but over-expressed by systemic metastatic colorectal tumors. Here, we reveal that GUCY2C rapidly internalizes from the cell surface to lysosomes in intestinal and colorectal cancer cells. Endocytosis is independent of ligand binding and receptor activation, and is mediated by clathrin. This mechanism suggests a design for …

Tp53 Mutations Detected In Circulating Tumor Cells Present In The Blood Of Metastatic Triple Negative Breast Cancer Patients., Sandra V Fernandez, Catherine Bingham, Patricia Fittipaldi, Laura Austin, Juan P. Palazzo, Gary Palmer, Katherine Alpaugh, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Circulating tumor cells (CTCs) are tumor cells shed from either primary tumors or its metastases that circulate in the peripheral blood of patients with metastatic cancers. The molecular characterization of the CTCs is critical to identifying the key drivers of cancer metastasis and devising therapeutic approaches. However, the molecular characterization of CTCs is difficult to achieve because their isolation is a major technological challenge.

METHODS: CTCs from two triple negative breast cancer patients were enriched using CellSearch and single cells selected by DEPArray™. A TP53 R110 fs*13 mutation identified by next generation sequencing in the breast and chest skin …

Subgroups Of Cancer Patients With Unique Pain And Fatigue Experiences During Chemotherapy, Heeju Kim, Patrick S. Malone, Andrea M. Barsevick

Department of Medical Oncology Faculty Papers

Context. Some cancer patients experience pain and fatigue, whereas others experience only one of the two symptoms. Yet, it is not clear who experiences these unique patterns and why.

Objectives. This study aimed to identify subgroups of cancer patients with unique pain and fatigue experiences in two different chemotherapy cycles to examine how selected factors influenced subgroup membership and identify how subgroups differed in concurrently measured functional limitation outcome.

Methods. The sample included 276 patients with diverse cancer types from four U.S. sites. To investigate subgroups, latent profile analyses were performed. Multinomial logistic regression and one-way analysis of variance-type analyses …

Association Of Leukocyte Mitochondrial Dna Content With Glioma Risk: Evidence From A Chinese Case-Control Study., Jie Zhang, Deyang Li, Falin Qu, Yibing Chen, Gang Li, Hequn Jiang, Xiaojun Huang, Hushan Yang, Jinliang Xing

Department of Cancer Biology Faculty Papers

BACKGROUND: Increasing evidence suggests that alterations in mitochondrial DNA (mtDNA) content may be implicated in the tumorigenesis of several malignancies. However, the association between mtDNA content in peripheral blood lymphocytes (PBLs) and glioma risk has not been investigated.

METHODS: Real-time PCR was used to examine the mtDNA content in PBLs of 414 glioma patients and 414 matched controls in a hospital-based case-control study. The association between mtDNA content and glioma risk was evaluated using an unconditional multivariate logistic regression model.

RESULTS: We found that glioma patients exhibited a significantly higher median mtDNA content than healthy controls (0.99 vs. 0.71, P …

Circulating Tumor Cells As Early Predictors Of Metastatic Spread In Breast Cancer Patients With Limited Metastatic Dissemination., Mario Giuliano, Antonio Giordano, Summer Jackson, Ugo De Giorgi, Michal Mego, Evan N Cohen, Hui Gao, Simone Anfossi, Beverly C Handy, Naoto T Ueno, Ricardo H Alvarez, Sabino De Placido, Vicente Valero, Gabriel N Hortobagyi, James M Reuben, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

IntroductionTraditional factors currently used for prognostic stratification do not always predict adequately treatment response and disease evolution in advanced breast cancer patients. Therefore, the use of blood-based markers, such as circulating tumor cells (CTCs), represents a promising complementary strategy for disease monitoring. In this retrospective study, we explored the role of CTC counts as predictors of disease evolution in breast cancer patients with limited metastatic dissemination.Methods492 advanced breast cancer patients who had a CTC count assessed by CellSearch prior to starting a new line of systemic therapy were eligible for this analysis. Using the threshold of 5 cells/7.5 mL of …

Acetylation-Defective Mutant Of Pparγ Is Associated With Decreased Lipid Synthesis In Breast Cancer Cells., Lifeng Tian, Chenguang Wang, Fred K Hagen, Michael Gormley, Sankar Addya, Raymond Soccio, Mathew C Casimiro, Jie Zhou, Michael J Powell, Ping Xu, Haiteng Deng, Anthony A Sauve, Richard Pestell

Department of Cancer Biology Faculty Papers

In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was …

Parp-2 And Parp-3 Are Selectively Activated By 5' Phosphorylated Dna Breaks Through An Allosteric Regulatory Mechanism Shared With Parp-1., Marie-France Langelier, Amanda A Riccio, John M Pascal

Department of Biochemistry and Molecular Biology Faculty Papers

PARP-1, PARP-2 and PARP-3 are DNA-dependent PARPs that localize to DNA damage, synthesize poly(ADP-ribose) (PAR) covalently attached to target proteins including themselves, and thereby recruit repair factors to DNA breaks to increase repair efficiency. PARP-1, PARP-2 and PARP-3 have in common two C-terminal domains-Trp-Gly-Arg (WGR) and catalytic (CAT). In contrast, the N-terminal region (NTR) of PARP-1 is over 500 residues and includes four regulatory domains, whereas PARP-2 and PARP-3 have smaller NTRs (70 and 40 residues, respectively) of unknown structural composition and function. Here, we show that PARP-2 and PARP-3 are preferentially activated by DNA breaks harboring a 5' phosphate …

The Tumor Suppressive Role Of Camk2n1 In Castration-Resistant Prostate Cancer., Tao Wang, Zhuo Liu, Shuiming Guo, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Shaohua Xu, Liping Wang, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen

Department of Cancer Biology Faculty Papers

Prostate cancer at advanced stages including metastatic and castration-resistant cancer remains incurable due to the lack of effective therapies. The CAMK2N1 gene, cloned and characterized as an inhibitor of CaMKII (calcium/calmodulin-dependent protein kinase II), has been shown to affect tumorigenesis and tumor growth. However, it is still unknown whether CAMK2N1 plays a role in prostate cancer development. We first examined the protein and mRNA levels of CAMK2N1 and observed a significant decrease in human prostate cancers comparing to normal prostate tissues. Re-expression of CAMK2N1 in prostate cancer cells reduced cellular proliferation, arrested cells in G0/G1 phases, and induced apoptotic cell …

Micrornas: The Short Link Between Cancer And Rt-Induced Dna Damage Response., Christopher M Wright, Tu Dan, Adam Dicker Md, Phd, Nicole L Simone

Department of Radiation Oncology Faculty Papers

No abstract provided.

Results Of A Phase I Study Of Bendamustine In Combination With Ofatumumab, Carboplatin And Etoposide (Boce) For Refractory Of Relapsed Aggressive B-Cell Non Hodgkin's Lymphomas (Nhl), Sameh Gaballa, Md, Neil D. Palmisiano, Md, Aakanksha Asija, Md, Andrew Chapman, Do, Jennifer K. Cloud, Bs, Joanne Filicko-O'Hara, Md, Lewis Rose, Md, Michael Ramirez, Md, Onder Alpdogan, Md, Neal Flomenberg, Md, Barbara Pro, Md, Elena Gitelson, Md, Phd, Mark Weiss, Md

Department of Medical Oncology Faculty Papers

Introduction:

• There are a number of regimens used to treat relapsed/refractory aggressive lymphomas and little consensus exists on the best salvage treatment.
• No regimen has shown clear superiority but uniformly there was an inferior outcome among patients who had relapsed after a prior rituximab containing regimen.
• Ofatumumab is a fully human IgG1k monoclonal anti-CD20 antibody. It recognizes a distinct epitope on the human CD20 molecule. In vitro studies with ofatumumab have shown more complement dependent cytotoxicity than rituximab.
• Bendamustine has single agent activity in relapsed aggressive lymphomas and has a favorable safety profile.

Objectives:

• We conducted a phase I trial …

Mir-221/222 Promotes S-Phase Entry And Cellular Migration In Control Of Basal-Like Breast Cancer., Yuan Li, Chunli Liang, Haizhong Ma, Qian Zhao, Ying Lu, Zhendong Xiang, Li Li, Jie Qin, Yihan Chen, William C Cho, Richard G Pestell, Li Liang, Zuoren Yu

Department of Cancer Biology Faculty Papers

The miR-221/222 cluster has been demonstrated to function as oncomiR in human cancers. miR-221/222 promotes epithelial-to-mesenchymal transition (EMT) and confers tamoxifen resistance in breast cancer. However, the effects and mechanisms by which miR-221/222 regulates breast cancer aggressiveness remain unclear. Here we detected a much higher expression of miR-221/222 in highly invasive basal-like breast cancer (BLBC) cells than that in non-invasive luminal cells. A microRNA dataset from breast cancer patients indicated an elevated expression of miR-221/222 in BLBC subtype. S-phase entry of the cell cycle was associated with the induction of miR-221/222 expression. miRNA inhibitors specially targeting miR-221 or miR-222 both …

An Update On Breast Cancer Screening And Prevention., Maria Syl D. De La Cruz, Mona Sarfaty, Richard C Wender

Department of Family & Community Medicine Faculty Papers

The goal of this article is to provide clinical guidance on breast cancer screening and prevention in primary care. The discussion highlights the importance of risk assessment, including screening options and risk-reduction strategies, for women at average and high risk. We review recommendations for breast cancer screening, evaluate current evidence on primary prevention, examine current practice patterns, and consider the impact of recent changes within health care.

Azd8931, An Equipotent, Reversible Inhibitor Of Signaling By Epidermal Growth Factor Receptor (Egfr), Her2, And Her3: Preclinical Activity In Her2 Non-Amplified Inflammatory Breast Cancer Models., Zhaomei Mu, Teresa Klinowska, Xiaoshen Dong, Emily Foster, Chris Womack, Sandra V Fernandez, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Epidermal growth factor receptor (EGFR) overexpression has been associated with prognostic and predictive value in inflammatory breast cancer (IBC). Epidermal growth factor receptor 2 (HER2) overexpression is observed at a higher rate in IBC compared with noninflammatory breast cancer. Current clinically available anti-HER2 therapies are effective only in patients with HER2 amplified breast cancer, including IBC. AZD8931 is a novel small-molecule equipotent inhibitor of EGFR, HER2, and HER3 signaling. In this study, we investigated the antitumor activity of AZD8931 alone or in combination with paclitaxel using preclinical models of EGFR-overexpressed and HER2 non-amplified IBC cells.

METHODS: Two IBC cell …

Pharmacologic Suppression Of Jak1/2 By Jak1/2 Inhibitor Azd1480 Potently Inhibits Il-6-Induced Experimental Prostate Cancer Metastases Formation., Lei Gu, Pooja Talati, Paraskevi Vogiatzi, Ana L Romero-Weaver, Junaid Abdulghani, Zhiyong Liao, Benjamin E. Leiby, David T. Hoang, Tuomas Mirtti, Kalle Alanen, Michael Zinda, Dennis Huszar, Marja T. Nevalainen

Department of Medical Oncology Faculty Papers

Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by multiple studies. However, the direct functional roles of IL-6 in prostate cancer growth and progression have been unclear. In the present study, we show that IL-6 is produced in distant metastases of clinical prostate cancers. IL-6-activated signaling pathways in prostate cancer cells induced a robust 7-fold increase in metastases formation in nude mice. We further show that IL-6 promoted migratory prostate cancer cell phenotype, including increased prostate cancer cell …

Thermal Dosimetry Characteristics Of Deep Regional Heating Of Non-Muscle Invasive Bladder Cancer., Titania Juang, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Yu Yuan, Shiva K Das, Mark W Dewhirst, Brant A Inman, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: The aim of this paper is to report thermal dosimetry characteristics of external deep regional pelvic hyperthermia combined with intravesical mitomycin C (MMC) for treating bladder cancer following transurethral resection of bladder tumour, and to use thermal data to evaluate reliability of delivering the prescribed hyperthermia dose to bladder tissue.

MATERIALS AND METHODS: A total of 14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma Ellipse or Sigma 60). The hyperthermia objective was 42° ± 2 °C to bladder tissue for ≥40 min per treatment. Temperatures were monitored with thermistor probes and recorded values were used …

A Pilot Clinical Trial Of Intravesical Mitomycin-C And External Deep Pelvic Hyperthermia For Non-Muscle-Invasive Bladder Cancer., Brant A Inman, Paul R. Stauffer, Oana A Craciunescu, Paolo F Maccarini, Mark W Dewhirst, Zeljko Vujaskovic

Department of Radiation Oncology Faculty Papers

PURPOSE: This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC).

MATERIALS AND METHODS: We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured.

RESULTS: Fifteen patients were …

Outcomes Of Older Patients Undergoing 2-Step Approach To Haploidentical And Matched Related Peripheral Blood Hematopoietic Stem Cell Transplantation (Hsct): A Single Institutional Experience, Sameh Gaballa, Md, Seyfettin Onder Alpdogan, Md, Matthew Carabasi, Md, Joanne Filicko-O'Hara, Md, Margaret Kasner, Md, Benjamin E Leiby, Phd, Ubaldo E. Martinez-Outshoorn, Md, Edward C Pequignot, Md, Sarah Rosado, Shannon Rudolph, Ms, John L Wagner, Md, Mark Weiss, Md, Neal Flomenberg, Md, Dolores Grosso, Dnp

Department of Medical Oncology Faculty Papers

Introduction:

HSCT is a curative option for many patients (pts) with hematological malignancies.

Significant advances in supportive care and conditioning regimens over the past decade have allowed the extension of this therapy to older individuals.

Information regarding the outcomes of this older subset of pts undergoing HSCT is limited, especially those undergoing haploidential (HI) HSCT.

Objectives:

To describe the outcomes of patients 60 years of age or older undergoing haploidential and matched related (MR) HSCT using the 2-step approach.

A Long-Term Study Of The Effects Of Antiviral Therapy On Survival Of Patients With Hbv-Associated Hepatocellular Carcinoma (Hcc) Following Local Tumor Ablation., Hie-Won Hann, Robert Coben, Daniel Brown, Laurence Needleman, Ernest Rosato, Albert Min, Richard Hann, Kyong Bin Park, Stephen Dunn, Anthony J. Dimarino

Department of Medicine Faculty Papers

The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed …

Cell-Mediated Immunity And Vaccines, Jaya Kumari, Senthamil R. Selvan, Stéphane Bécart, Subhasis Chattopadhyay, Roy Ambli Dalmo

Department of Medical Oncology Faculty Papers

No abstract provided.

A Novel Radiation-Induced P53 Mutation Is Not Implicated In Radiation Resistance Via A Dominant-Negative Effect., Yunguang Sun, Carey Jeanne Myers, Adam Dicker Md, Phd, Bo Lu, Md

Department of Radiation Oncology Faculty Papers

Understanding the mutations that confer radiation resistance is crucial to developing mechanisms to subvert this resistance. Here we describe the creation of a radiation resistant cell line and characterization of a novel p53 mutation. Treatment with 20 Gy radiation was used to induce mutations in the H460 lung cancer cell line; radiation resistance was confirmed by clonogenic assay. Limited sequencing was performed on the resistant cells created and compared to the parent cell line, leading to the identification of a novel mutation (del) at the end of the DNA binding domain of p53. Levels of p53, phospho-p53, p21, total caspase …

Targeting Fibroblast Activation Protein In Tumor Stroma With Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth And Augment Host Immunity Without Severe Toxicity., Liang-Chuan S. Wang, Albert Lo, John Scholler, Jing Sun, Rajrupa S. Majumdar, Veena Kapoor, Michael Antzis, Cody E. Cotner, Laura A. Johnson, Amy C. Durham, Charalambos C. Solomides, Md, Carl H. June, Ellen Puré, Steven M. Albelda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the …

Measuring Patient Satisfaction In Multidisciplinary Cancer Centers: Optimize Use Of Results To Effect Change And Improve Processes, Mary-Kate Cellmer, Bs

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Jefferson¹s Kimmel Cancer Center¹s multidisciplinary centers were established in 1994. The centers are a collaborative effort among radiation oncologists, medical oncologists, surgeons and other specialists involved in leading-edge cancer treatments.

The multidisciplinary center sees patients on the following days:

• Monday: Brain and Metastatic Uveal Melanoma
• Tuesday: Thoracic/Aerodigestive and Senior Adult Oncology
• Wednesday: Genitourinary and Liver
• Thursday: Small Renal Mass
• Friday: Senior Adult Oncology