Medicine and Health Sciences Commons^™

Ribonucleotide Reductase Inhibitor 3-Ap Induces Oncogenic Virus Infected Cell Death And Represses Tumor Growth, Lu Dai, Jungang Chen, Yueyu Cao, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human malignancies, particularly Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation while still lacking of effective therapeutic options. We recently found that the ribonucleotide reductase (RR) subunit M2 is potentially regulated by the key oncogenic HGF/c-MET pathway in KSHV-related lymphoma cells. One of RR inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) effectively induced apoptosis of KSHV+ lymphomas and suppressed tumor progression . In the current study, we found that 3-AP treatment selectively inhibited the proliferation of KSHV-infected endothelial cells, the major cellular components of KS, through inducing DNA …

Implantable Biomaterials To Provide Local Immunotherapy Following Surgical Resection., Michael J Gough, Jason R Baird, R Bryan Bell

Articles, Abstracts, and Reports

No abstract provided.

Targeted Therapies For Advanced Non-Small Cell Lung Cancer, Xiaojuan Ai, Xialing Guo, Jun Wang, Andreea L Stancu, Patrick M N Joslin, Dianzheng Zhang, Shudong Zhu

PCOM Scholarly Papers

Lung cancer is a serious health problem and the leading cause of cancer death worldwide, due to its high incidence and mortality. 85% of lung cancers are represented by the non-small cell lung cancer (NSCLC). Traditional chemotherapy has been the main treatment option in NSCLC. However, it is often associated with limited efficacy and overall poor patient survival. In recent years, molecular targeting has achieved great progress in therapeutic treatment of cancer and plays a crucial role in the current clinical treatment of NSCLC, due to enhanced efficacy on cancer tissues and reduced toxicity for normal tissues. In this review, …

Prognostic Relevance Of Ccdc88c (Daple) Transcripts In The Peripheral Blood Of Patients With Cutaneous Melanoma, Ying Dunkel, Anna L. Reid, Jason Ear, Nicolas Aznar, Michael Millward, Elin Gray, Robert Pearce, Melanie Ziman, Pradipta Ghosh

Research outputs 2014 to 2021

A loss of balance between G protein activation and deactivation has been implicated in the initiation of melanomas, and non-canonical Wnt signaling via the Wnt5A/Frizzled (FZD) pathway has been shown to be critical for the switch to an invasive phenotype. Daple [CCDC88C], a cytosolic guanine nucleotide exchange modulator (GEM) which enhances non-canonical Wnt5A/FZD signaling via activation of trimeric G protein, Gαi, has been shown to serve opposing roles-as an inducer of EMT and invasiveness and a potent tumor suppressor-via two isoforms, V1 (full-length) and V2 (short spliced isoform), respectively. Here we report that the relative abundance of these isoforms in …

Mechanical Suppression Of Osteolytic Bone Metastases In Advanced Breast Cancer Patients: A Randomised Controlled Study Protocol Evaluating Safety, Feasibility And Preliminary Efficacy Of Exercise As A Targeted Medicine, Nicolas H. Hart, Daniel A. Galvão, Christobel Saunders, Dennis R. Taaffe, Kynan T. Feeney, Nigel A. Spry, Daphne Tsoi, Hilary Martin, Raphael Chee, Tim Clay, Andrew D. Redfern, Robert U. Newton

Research outputs 2014 to 2021

BACKGROUND: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising …

Spio Enhance The Cross-Presentation And Migration Of Dcs And Anionic Spio Influence The Nanoadjuvant Effects Related To Interleukin-1Β., Hui Liu, Heng Dong, Na Zhou, Shiling Dong, Lin Chen, Yanxiang Zhu, Hong-Ming Hu, Yongbin Mou

Articles, Abstracts, and Reports

Superparamagnetic iron oxide nanoparticles (SPIO) have been synthesized and explored for use as carriers of various nanoadjuvants via loading into dendritic cells (DCs). In our study, homogeneous and superparamagnetic nanoparticles are susceptible to internalization by DCs and SPIO-pulsed DCs showed excellent biocompatibility and capacity for ovalbumin (OVA) cross-presentation. Herein, we found that SPIO-loaded DCs can promote the maturation and migration of DCs in vitro. SPIO coated with 3-aminopropyltrimethoxysilane (APTS) and meso-2,3-dimercaptosuccinic acid (DMSA), which present positive and negative charges, respectively, were prepared. We aimed to investigate whether the surface charge of SPIO can affect the antigen cross-presentation of the DCs. …

Regulators Of Oncogenic Mutant Tp53 Gain Of Function., Satomi Yamamoto, Tomoo Iwakuma

Manuscripts, Articles, Book Chapters and Other Papers

The tumor suppressor p53 (TP53) is the most frequently mutated human gene. Mutations in TP53 not only disrupt its tumor suppressor function, but also endow oncogenic gain-of-function (GOF) activities in a manner independent of wild-type TP53 (wtp53). Mutant TP53 (mutp53) GOF is mainly mediated by its binding with other tumor suppressive or oncogenic proteins. Increasing evidence indicates that stabilization of mutp53 is crucial for its GOF activity. However, little is known about factors that alter mutp53 stability and its oncogenic GOF activities. In this review article, we primarily summarize key regulators of mutp53 stability/activities, including genotoxic stress, post-translational modifications, ubiquitin …

Tumor Cell-Released Autophagosomes (Traps) Promote Immunosuppression Through Induction Of M2-Like Macrophages With Increased Expression Of Pd-L1., Zhi-Fa Wen, Hongxiang Liu, Rong Gao, Meng Zhou, Jie Ma, Yue Zhang, Jinjin Zhao, Yongqiang Chen, Tianyu Zhang, Fang Huang, Ning Pan, Jinping Zhang, Bernard A Fox, Hong-Ming Hu, Li-Xin Wang

Articles, Abstracts, and Reports

BACKGROUND: Tumor-associated macrophages (TAMs) facilitate tumor progression via establishment of an immunosuppressive tumor microenvironment (TME). However, it is poorly understood how tumor cells could functionally modulate TAMs. Our previous work indicated that tumor cell-released autophagosomes (TRAPs), a type of LC3-II

METHODS: TRAPs isolated from multiple murine tumor cell lines and pleural effusions or ascites of cancer patients were incubated with bone marrow-derived macrophages (BMDMs) and monocytes, respectively. Cellular phenotypes were examined by flow cytometry, ELISA and quantitative PCR. TRAPs treated BMDMs were tested for the ability to suppress T-cell proliferation in vitro, and for promotion of tumor growth in vivo. …

Rare But Recurrent Ros1 Fusions Resulting From Chromosome 6q22 Microdeletions Are Targetable Oncogenes In Glioma., Monika A Davare, Jacob J Henderson, Anupriya Agarwal, Jacob P Wagner, Sudarshan R Iyer, Nameeta Shah, Randy Woltjer, Romel Somwar, Stephen W Gilheeney, Ana Decarvalo, Tom Mikkelson, Erwin G Van Meir, Marc Ladanyi, Brian J Druker

Articles, Abstracts, and Reports

PURPOSE: Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.

EXPERIMENTAL DESIGN: Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset. Functional validation of the oncogenic potential and inhibitory sensitivity of discovered ROS1 fusions was performed using three independent cell-based model systems, and an

RESULTS:

CONCLUSIONS: Our findings highlight that CNS tumors should be specifically interrogated for these rare intrachromosomal 6q22 microdeletion …

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

Precision Medicine In Pediatric Cancer: Current Applications And Future Prospects., Atif Ahmed, Divya S. Vundamati, Midhat S. Farooqi, Erin M. Guest

Manuscripts, Articles, Book Chapters and Other Papers

Precision oncologic medicine is an emerging approach for cancer treatment that has recently taken giant steps in solid clinical practice. Recent advances in molecular diagnostics that can analyze the individual tumor's variability in genes have provided greater understanding and additional strategies to treat cancers. Although tumors can be tested by several molecular methods, the use of next-generation sequencing (NGS) has greatly facilitated our understanding of pediatric cancer and identified additional therapeutic opportunities. Pediatric tumors have a different genetic make-up, with a fewer number of actionable targets than adult tumors. Nevertheless, precision oncology in the pediatric population has greatly improved the …

Author Correction: Extracting Intercellular Signaling Network Of Cancer Tissues Using Ligand-Receptor Expression Patterns From Whole-Tumor And Single-Cell Transcriptomes., Joseph X Zhou, Roberto Taramelli, Edoardo Pedrini, Theo Knijnenburg, Sui Huang

Articles, Abstracts, and Reports

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi

Molecular and Cellular Biochemistry Faculty Publications

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …

Notch Signaling Regulates Mitochondrial Metabolism And Nf-Κb Activity In Triple-Negative Breast Cancer Cells Via Ikkα-Dependent Non-Canonical Pathways, Fokhrul Hossain, Claudia Sorrentino, Deniz A. Ucar, Yin Peng, Margarite Matossian, Dorota Wyczechowska, Judy Crabtree, Jovanny Zabaleta, Silvana Morello, Luis Del Valle, Matthew Burow, Bridgette Collins-Burow, Antonio Pannuti, Lisa M. Minter, Todd E. Golde, Barbara A. Osborne, Lucio Miele

School of Medicine Faculty Publications

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown. We studied the role of the AKT pathway and mitochondrial metabolism downstream of Notch signaling in TNBC CSC from cell lines representative of different TNBC molecular subtypes as well as …

Sitc 2018 Workshop Report: Immuno-Oncology Biomarkers: State Of The Art., Lisa H Butterfield, Mary L Disis, Bernard A Fox, David R Kaufman, Samir N Khleif, Ena Wang

Articles, Abstracts, and Reports

Identification of biomarkers in cancer immunotherapy that predict therapeutic response and/or limit adverse events are a critical need in the field. To address recent progress and hurdles around cancer biomarker development and utilization, the Society for Immunotherapy of Cancer (SITC) convened a workshop, "Immuno-Oncology Biomarkers: State of the Art," on May 16-17, 2018. Topics discussed included challenges in handling biospecimens, identification and validation of new biomarkers, data sharing, and collaborating across disciplines to advance biomarker development. Panel discussions followed session presentations to help foster participant conversation and discuss future projects and collaborations. The results of the Workshop include the development …

Targeting The Stat5 Pathway In Ph+ Acute Lymphoblastic Leukemia, Valentina Minieri, Marco De Dominici, Marja T. Nevalainen, Bruno Calabretta

Department of Cancer Biology Faculty Papers

No abstract provided.

Global Availability Of Cancer Registry Data., Asif H. Siddiqui, Syed Nabeel Zafar

Medical College Documents

The availability of cancer registries has significantly enhanced cancer research, especially that related to cancer epidemiology, survival, interventions, and outcomes.1 However, by using publicly available sources, we aimed to map the availability and extent of cancer registry data in each country. We also aimed to test the association of registry data with metadata such as country income and national cancer-related policies. Data from 190 countries were collected from the WHO country cancer profiles.2 We sought data on the presence of an operational national cancer control policy, strategy, or action plan and the presence of a cancer registry. If those data …

The Hungry Cancer Patient: A Case Of Money Ill Spent., Allison Zibelli

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

No abstract provided.

The Impact Of Mental Health On Cancer Preventative Screenings, Chelsea Edirisuriya, Amy Leader, Phd

Phase 1

Among the mental health population of the United States, overall preventative health services, such as cancer screening rates, are remarkably low. Additionally, there is a significant 30% higher mortality rate due to cancer in psychiatric patients. This project established if there are disparities in cancer screening rates between the general population and the mental health population of Southeastern Pennsylvania. The project analyzed and compared the differences in cancer screenings for colorectal, breast, and cervical cancer among those currently diagnosed with a mental condition and the general population. Through p-value and Pearson chi-square statistical analysis of the Community Health Data Base …

A Learning Community Approach To Identifying Interventions In Health Systems To Reduce Colorectal Cancer Screening Disparities., Lillian C. Man, Melissa Dicarlo, Emily Lambert, Randa Sifri, Martha Romney, Linda Fleisher, Ronald Myers

Department of Medical Oncology Faculty Papers

Although colorectal cancer (CRC) screening in the United States has been increasing, screening rates are not optimal, and there are persistent disparities in CRC screening and mortality, particularly among minority patients. As most CRC screening takes place in primary care, health systems are well-positioned to address this important population health problem. However, most health systems have not actively engaged in identifying and implementing effective evidence-based intervention strategies that can raise CRC screening rates and reduce disparities. Drawing on the Collective Impact Model and the Interactive Systems Framework for Dissemination and Implementation, our project team applied a learning community strategy to …

Spaceoar To Improve Dosimetric Outcomes For Monotherapy High-Dose-Rate Prostate Implantation In A Patient With Ulcerative Colitis., Michael Trager, Benjamin Greenberger, Amy S. Harrison, James Keller, Robert B. Den

Department of Radiation Oncology Faculty Papers

High-dose-rate (HDR) brachytherapy is an attractive option for patients receiving definitive radiation therapy for prostate cancer with decreased overall dose to the pelvis. However, ulcerative colitis increases rectal toxicity risk and may be a contraindication. A synthetic hydrogel, SpaceOAR (Augmentix Inc., Waltham, MA, USA), can facilitate the use of HDR brachytherapy for patients where rectal toxicity is a limiting factor. SpaceOAR gel (13.19 cc) was utilized in a monotherapy HDR prostate treatment with Ir-192 under transrectal ultrasound guidance, with the intention of decreasing rectal dose. SpaceOAR gel was inserted transperineally into the patient 18 days prior to the procedure. The …

Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller

Bioelectrics Publications

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell …

Challenges Faced By Pakistani Healthcare System: Clinician's Perspective, Faran Khalid, Ahmed Nadeem Abbasi

Department of Radiation Oncology

Abstract are not provided by the author/publisher

Emt- And Stroma-Related Gene Expression And Resistance To Pd-1 Blockade In Urothelial Cancer., Li Wang, Abdel Saci, Peter M. Szabo, Scott D. Chasalow, Mireia Castillo-Martin, Josep Domingo-Domenech, Arlene Siefker-Radtke, Padmanee Sharma, John P. Sfakianos, Yixuan Gong, Ana Dominguez-Andres, William K. Oh, David Mulholland, Alex Azrilevich, Liangyuan Hu, Carlos Cordon-Cardo, Hélène Salmon, Nina Bhardwaj, Jun Zhu, Matthew D. Galsky

Department of Cancer Biology Faculty Papers

Cancers infiltrated with T-cells are associated with a higher likelihood of response to PD-1/PD-L1 blockade. Counterintuitively, a correlation between epithelial-mesenchymal transition (EMT)-related gene expression and T-cell infiltration has been observed across tumor types. Here we demonstrate, using The Cancer Genome Atlas (TCGA) urothelial cancer dataset, that although a gene expression-based measure of infiltrating T-cell abundance and EMT-related gene expression are positively correlated, these signatures convey disparate prognostic information. We further demonstrate that non-hematopoietic stromal cells are a major source of EMT-related gene expression in bulk urothelial cancer transcriptomes. Finally, using a cohort of patients with metastatic urothelial cancer treated with …

Effect Of Differences In Metabolic Activity Of Melanoma Models On Response To Lonidamine Plus Doxorubicin., Kavindra Nath, Jeffrey Roman, David S. Nelson, Lili Guo, Seung-Cheol Lee, Stepan Orlovskiy, Kevin Muriuki, Daniel F. Heitjan, Stephen Pickup, Dennis B. Leeper, Ian A. Blair, Mary E. Putt, Jerry D. Glickson

Department of Radiation Oncology Faculty Papers

Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than WM983B in vitro. ³¹P magnetic resonance spectroscopy (MRS) indicates that LND (100 mg/kg, i.p.) induces similar selective acidification and de-energization of WM983B xenografts in immunosuppressed mice. Over three hours, intracellular pH (pHi) of WM983B decreased from 6.91 ± 0.03 to 6.59 ± 0.10 (p …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

Comparison Of Germline Versus Somatic Bap1 Mutations For Risk Of Metastasis In Uveal Melanoma., K. G. Ewens, E. Lalonde, J. Richards-Yutz, C. L. Shields, A. Ganguly

Wills Eye Hospital Papers

BACKGROUND: Germline mutations in BAP1 have been associated with BAP1-Tumor Predisposition Syndrome (BAP1-TPDS), a predisposition to multiple tumors within a family that includes uveal melanoma (UM), cutaneous melanoma, malignant mesothelioma and renal cell carcinoma. Alternatively, somatic mutations in BAP1 in UM have been associated with high risk for metastasis. In this study, we compare the risk of metastasis in UM that carry germline versus somatic BAP1 mutations and mutation-negative tumors.

METHODS: DNA extracted from 142 UM and matched blood samples was sequenced using Sanger or next generation sequencing to identify BAP1 gene mutations.

RESULTS: Eleven of 142 UM (8%) carried …

Semaphorin 5a Drives Melanoma Progression: Role Of Bcl-2, Mir-204 And C-Myb., Simona D'Aguanno, Elisabetta Valentini, Maria Grazia Tupone, Marianna Desideri, Marta Di Martile, Manuela Spagnuolo, Simonetta Buglioni, Cristiana Ercolani, Italia Falcone, Marco De Dominici, Michele Milella, Maria Giulia Rizzo, Bruno Calabretta, Carlo Cota, Andrea Anichini, Daniela Trisciuoglio, Donatella Del Bufalo

Department of Cancer Biology Faculty Papers

BACKGROUND: Melanoma, the most aggressive form of skin cancer, is characterized by high rates of metastasis, drug resistance and mortality. Here we investigated the role of Semaphorin 5A (Sema5A) on the properties associated with melanoma progression and the factors involved in Sema5A regulation.

METHODS: Western blotting, qRT-PCR, Chromatin immunoprecipitation (ChIP) assay, immunohistochemistry of melanoma patient specimens and xenograft tissues, in vitro Transwell assay for cell migration and invasion evaluation, in vitro capillary-like structure formation analysis.

RESULTS: A significant correlation of Sema5A mRNA expression and melanoma progression was observed by analyzing GEO profile dataset. Endogenous Sema5A protein was detected in 95% …

Hnrnpa2 Mediated Acetylation Reduces Telomere Length In Response To Mitochondrial Dysfunction, Manti Guha, Satish Srinivasan, F. Bradley Johnson, Gordon Ruthel, Kip Guja, Miguel Garcia-Diaz, Brett A. Kaufman, M. Rebecca Glineburg, Jikang Fang, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Telomeres protect against chromosomal damage. Accelerated telomere loss has been associated with premature aging syndromes such as Werner’s syndrome and Dyskeratosis Congenita, while, progressive telomere loss activates a DNA damage response leading to chromosomal instability, typically observed in cancer cells and senescent cells. Therefore, identifying mechanisms of telomere length maintenance is critical for understanding human pathologies. In this paper we demonstrate that mitochondrial dysfunction plays a causal role in telomere shortening. Furthermore, hnRNPA2, a mitochondrial stress responsive lysine acetyltransferase (KAT) acetylates telomere histone H4at lysine 8 of (H4K8) and this acetylation is associated with telomere attrition. Cells containing dysfunctional mitochondria …

Myeloablative Vs Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation For Chronic Myeloid Leukemia, Saurabh Chhabra, Kwang Woo Ahn, Zhen-Huan Hu, Sandeep Jain, Amer Assal, Jan Cerny, Edward A. Copelan, Andrew Daly, Zachariah Defilipp, Shahinaz M Gadalla, Robert Peter Gale, Siddhartha Ganguly, Betty K. Hamilton, Gerhard C. Hildebrandt, Jack W. Hsu, Yoshihiro Inamoto, Abraham S. Kanate, H. Jean Khoury, Hillard M. Lazarus, Mark R. Litzow, Sunita Nathan, Richard F. Olsson, Attaphol Pawarode, Olle Ringden, Jacob M. Rowe, Ayman Saad, Bipin N. Savani, Harry C. Schouten, Sachiko Seo, Nirav N. Shah

Markey Cancer Center Faculty Publications

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients …