Oncology Commons^™

Cyclophosphamide Induces Durable Molecular And Clinical Responses In Patients With Relapsed T-Lgl Leukemia., Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Jonathan E Brammer

Department of Medical Oncology Faculty Papers

No abstract provided.

Ocular Adnexal Lymphoma: A Single-Institution Retrospective Study, César A. Fernández, Roger K. Henry, Carol L. Shields, Jurij R. Bilyk, Sara E. Lally, Ralph C. Eagle, Tatyana Milman

Wills Eye Hospital Papers

PURPOSE: To characterize demographic, clinical, and histopathologic features of ocular adnexal lymphoma (OAL) at a single institution. METHODS: Retrospective review of all patients with pathologic diagnosis of OAL between 2015 and 2020. RESULTS: There were 133 patients with OAL, with a median age of 65 years (range 23-97) and a slight female predominance (male: female = 1:1.46), (n = 79, 59%). The majority of tumors were non-Hodgkin B-cell lymphomas (n = 131, 99%), most frequently Extranodal Marginal Zone B-Cell Lymphoma (EMZL, n = 93, 70%), followed by follicular lymphoma (n = 21, 16%), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = …

Therapeutic Resistance In Pancreatic Ductal Adenocarcinoma: Current Challenges And Future Opportunities, Aditi Jain, Phd, Vikas Bhardwaj

Kimmel Cancer Center Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancerrelated deaths in the United States. Although chemotherapeutic regimens such as gemcitabine+ nab-paclitaxel and FOLFIRINOX (FOLinic acid, 5-Fluroruracil, IRINotecan, and Oxaliplatin) significantly improve patient survival, the prevalence of therapy resistance remains a major roadblock in the success of these agents. This review discusses the molecular mechanisms that play a crucial role in PDAC therapy resistance and how a better understanding of these mechanisms has shaped clinical trials for pancreatic cancer chemotherapy. Specifically, we have discussed the metabolic alterations and DNA repair mechanisms observed in PDAC and current approaches in targeting …

Engaging Patients With Late-Stage Non-Small Cell Lung Cancer In Shared Decision Making About Treatment., Ronald E. Myers, Phd, Dsw, Shailesh M Advani, Pamela Myers, Preethi Selvan Mph Student, Gregory Garber, Msw, Lcsw, Brooke Worster, Md, Neal Flomenberg, Md, Andrew Chapman, Do, Ralph Zinner

Department of Medical Oncology Faculty Papers

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. …

Caring For Aml Patients During The Covid-19 Crisis: An American And Italian Experience., Lindsay Wilde, Md, Alessandro Isidori, Gina Keiffer, Md, Neil D. Palmisiano, Md, Margaret Kasner

Department of Medical Oncology Faculty Papers

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent pandemic have impacted every aspect of oncology care worldwide. Healthcare systems have been forced to rapidly change practices in order to maximize the safety of patients and healthcare providers and preserve scare resources. Patients with acute myeloid leukemia are at increased risk of complications from SARS-CoV-2 not only due to immune compromise related to the malignancy but also due to the acuity of the disease and intensity of treatment. These issues have created unique challenges during this difficult time. In this article, we present the approaches taken …

Targeting Homologous Recombination Addicted Tumors: Challenges And Opportunities, Talia Golan, Jonathan Brody, Md

Kimmel Cancer Center Faculty Papers

Recent advances in next generation sequencing (NGS) and molecular subtyping of tumors have opened the door to clinically available targeted therapies. Although the treatment of many solid tumors still rely on a steady regimen of non-targeted chemotherapeutic agents, it is becoming increasingly more apparent that certain tumors with defects in DNA damage repair (DDR) genes may be exquisitely sensitive to DNA damaging agents or therapies targeting key elements of this pathway such PARP1, ATR, or ATM. Still, for tumors with DDR defects the challenges are multi-fold including: (I) identifying these tumors in patients in time for a window of opportunity …

Racial Disparities In Head And Neck Cancers In An Urban Hospital, Jessica Kraus-Lavy, Charnita Zeigler-Johnson, Scott W Keith, Frances Guiles, David Cognetti, Voichita Bar-Ad, Rita S. Axelrod, Md

Phase 1

Introduction: Head and neck cancer incidence rates are higher for white residents in Philadelphia, while related mortality rates are highest for black residents. It is unclear how risk factors like HPV and smoking contribute to these disparities. The goal of this study is to determine which factors are associated with head and neck cancers in a diverse patient population from a Philadelphia hospital.

Methods: Cancer registry data from Thomas Jefferson University was used to obtain records from 922 head and neck cancer patients. One patient of other race was excluded. Twenty in-situ cancer cases were excluded. Chi-square tests were used …

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 …

Insights From Hur Biology Point To Potential Improvement For Second-Line Ovarian Cancer Therapy., Yu-Hung Huang, Weidan Peng, Narumi Furuuchi, James B Duhadaway, Masaya Jimbo, Andrea Pirritano, Charles J Dunton, Gary S Daum, Benjamin E Leiby, Jonathan Brody, Md, Janet A Sawicki

Kimmel Cancer Center Faculty Papers

This retrospective study aimed to investigate the role that an RNA-binding protein, HuR, plays in the response of high-grade serous ovarian tumors to chemotherapeutics. We immunohistochemically stained sections of 31 surgically-debulked chemo-naïve ovarian tumors for HuR and scored the degree of HuR cytoplasmic staining. We found no correlation between HuR intracellular localization in tumor sections and progression free survival (PFS) of these patients, 29 of whom underwent second-line gemcitabine/platin combination therapy for recurrent disease. Ribonucleoprotein immunoprecipitation (RNP-IP) analysis of ovarian cancer cells in culture showed that cytoplasmic HuR increases deoxycytidine kinase (dCK), a metabolic enzyme that activates gemcitabine. The effects …

The Effects Of Cep-37440, An Inhibitor Of Focal Adhesion Kinase, In Vitro And In Vivo On Inflammatory Breast Cancer Cells., Israa Salem, Manal Alsalahi, I Chervoneva, Lucy D Aburto, Sankar Addya, Gregory R Ott, Bruce A Ruggeri, Massimo Cristofanilli, Sandra V Fernandez

Department of Medical Oncology Faculty Papers

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive type of advanced breast cancer with a poor prognosis. We recently found that focal adhesion kinase 1 (FAK1) is upregulated and phosphorylated (active) in IBC. In this study, we investigated the effect of CEP-37440, a dual inhibitor of FAK1 and anaplastic lymphoma kinase (ALK), using human IBC cell lines and preclinical models of IBC.

METHODS: Cell proliferation assays were performed in the presence of several concentrations of CEP-37440 using IBC and triple-negative breast cancer non-IBC cell lines. In vitro, we studied the expression of total FAK1, phospho-FAK1 (Tyr 397), total ALK and …

New Podcast From Radiation Oncology, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The Department of Radiation Oncology’s first podcast, FAQ: Special focus on the Radiation Oncology Residency Program at Thomas Jefferson University, features a discussion of what separates Jefferson from other residency program and answers commonly asked questions. The podcast is now archived in the Jefferson Digital Commons.

Current State Of The Art Of Regional Hyperthermia Treatment Planning: A Review., H P Kok, P Wust, Paul R. Stauffer, F Bardati, G C Van Rhoon, J Crezee

Department of Radiation Oncology Faculty Papers

Locoregional hyperthermia, i.e. increasing the tumor temperature to 40-45 °C using an external heating device, is a very effective radio and chemosensitizer, which significantly improves clinical outcome. There is a clear thermal dose-effect relation, but the pursued optimal thermal dose of 43 °C for 1 h can often not be realized due to treatment limiting hot spots in normal tissue. Modern heating devices have a large number of independent antennas, which provides flexible power steering to optimize tumor heating and minimize hot spots, but manual selection of optimal settings is difficult. Treatment planning is a very valuable tool to improve …

Kinase Independent Oncogenic Cyclin D1., Mathew C Casimiro, Andrew Arnold, Richard Pestell

Kimmel Cancer Center Faculty Papers

No abstract provided.

Network-Based Stratification Analysis Of 13 Major Cancer Types Using Mutations In Panels Of Cancer Genes., Xue Zhong, Hushan Yang, Shuyang Zhao, Yu Shyr, Bingshan Li

Department of Medical Oncology Faculty Papers

BACKGROUND: Cancers are complex diseases with heterogeneous genetic causes and clinical outcomes. It is critical to classify patients into subtypes and associate the subtypes with clinical outcomes for better prognosis and treatment. Large-scale studies have comprehensively identified somatic mutations across multiple tumor types, providing rich datasets for classifying patients based on genomic mutations. One challenge associated with this task is that mutations are rarely shared across patients. Network-based stratification (NBS) approaches have been proposed to overcome this challenge and used to classify tumors based on exome-level mutations. In routine research and clinical applications, however, usually only a small panel of …

Consequence Of The Tumor-Associated Conversion To Cyclin D1b., Michael A Augello, Lisa D Berman-Booty, Richard Carr, Akihiro Yoshida, Jeffry L Dean, M J Schiewer, Felix Y Feng, Scott A Tomlins, Erhe Gao, Walter J Koch, Jeffrey L Benovic, John Alan Diehl, Karen E Knudsen

Department of Cancer Biology Faculty Papers

Clinical evidence suggests that cyclin D1b, a variant of cyclin D1, is associated with tumor progression and poor outcome. However, the underlying molecular basis was unknown. Here, novel models were created to generate a genetic switch from cyclin D1 to cyclin D1b. Extensive analyses uncovered overlapping but non-redundant functions of cyclin D1b compared to cyclin D1 on developmental phenotypes, and illustrated the importance of the transcriptional regulatory functions of cyclin D1b in vivo. Data obtained identify cyclin D1b as an oncogene, wherein cyclin D1b expression under the endogenous promoter induced cellular transformation and further cooperated with known oncogenes to promote …

Crosstalk Between Desmoglein 2 And Patched 1 Accelerates Chemical-Induced Skin Tumorigenesis., Donna M Brennan-Crispi, Claudia Hossain, Joya Sahu, Mary Brady, Natalia A Riobo, M G Mahoney

Department of Biochemistry and Molecular Biology Faculty Papers

Aberrant activation of Hedgehog (Hh) signaling is causative of BCCs and has been associated with a fraction of SCCs. Desmoglein 2 (Dsg2) is an adhesion protein that is upregulated in many cancers and overexpression of Dsg2 in the epidermis renders mice more susceptible to squamous-derived neoplasia. Here we examined a potential crosstalk between Dsg2 and Hh signaling in skin tumorigenesis. Our findings show that Dsg2 modulates Gli1 expression, in vitro and in vivo. Ectopic expression of Dsg2 on Ptc1+/lacZ background enhanced epidermal proliferation and interfollicular activation of the Hh pathway. Furthermore, in response to DMBA/TPA, the Dsg2/Ptc1+/lacZ mice developed squamous …

Assessment For Risk Factors Associated With Local Recurrence In Chordoma, John A. Abraham, Md, Wei Jiang, Md, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Chordoma is a rare but locally aggressive malignant neoplasm showing notochordal differentiation. The clinical differential diagnoses can be extensive, and definitive diagnosis often relies on histopathologic evaluation. Histologically, chordoma shows dual epithelial and mesenchymal differentiation, with various morphologies. Despite surgical resection and use of adjuvant radiation therapy, the local recurrence rate of chordoma remains high. We aim to establish factors associated with the increased risk of recurrence and help guide treatment decisions.

Phylogenetic Tree Construction And “Truncal Loss” Analysis Reveal Hidden Associations Between Loss Of Protein Expression In Swi/Snf Complex Components And Tumor Stage And Survival In Clear Cell Renal Cell Carcinoma (Ccrcc), Wei Jiang, Md, Phd, Essel Dulaimi, Karthik Devarajan, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Md, Stephen C Peiper, Phd, Robert Uzzo, Joseph R. Testa, Haifeng Yang, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Polybromo-1 (PBRM1), a targeting subunit of the SWI/SNF chromatin remodeling complex, is mutated at a rate of ~40% in clear cell Renal Cell Carcinoma (ccRCC), second only to VHL. Whether its mutation is correlated with tumor stage is controversial. As other components of the SWI/SNF complex were also reported to be mutated in ccRCC, we aim to examine the protein expression patterns of PBRM1, ARID1A, BRG1, and BRM in ccRCC, and to investigate possible association between their loss of expression and tumor stage, as well as survival. We also included a histone modifier, SETD2, which is recently discovered to …

Complementary And Alternative Medicine In Cancer Prevention And Therapy., Peng Cao, Senthamil R Selvan, Esra Küpeli Akkol, Ning Wang, Hongjun Yang, Xiaolan Cheng

Department of Medical Oncology Faculty Papers

No abstract provided.

Targeting Tumor-Initiating Cells: Eliminating Anabolic Cancer Stem Cells With Inhibitors Of Protein Synthesis Or By Mimicking Caloric Restriction., Rebecca Lamb, Hannah Harrison, Duncan L Smith, Paul A Townsend, Thomas Jackson, Bela Ozsvari, Ubaldo E. Martinez-Outshoorn, Md, Richard Pestell, Anthony Howell, Michael P. Lisanti, Federica Sotgia

Kimmel Cancer Center Faculty Papers

We have used an unbiased proteomic profiling strategy to identify new potential therapeutic targets in tumor-initiating cells (TICs), a.k.a., cancer stem cells (CSCs). Towards this end, the proteomes of mammospheres from two breast cancer cell lines were directly compared to attached monolayer cells. This allowed us to identify proteins that were highly over-expressed in CSCs and/or progenitor cells. We focused on ribosomal proteins and protein folding chaperones, since they were markedly over-expressed in mammospheres. Overall, we identified >80 molecules specifically associated with protein synthesis that were commonly upregulated in mammospheres. Most of these proteins were also transcriptionally upregulated in human …

Antibiotics For Cancer Therapy., Richard Pestell, Albert A Rizvanov

Department of Cancer Biology Faculty Papers

No abstract provided.

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 …

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; …

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 …

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 …

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.