A5053312423- Telomeres, Telomerase, and Senescence
- Neuroblastoma Research and Treatments
- Neuroendocrine Tumor Research Advances
- Prostate Cancer Treatment and Research
- Lung Cancer Research Studies
- Cytomegalovirus and herpesvirus research
- Glioma Diagnosis and Treatment
- Prostate Cancer Diagnosis and Treatment
- Molecular Biology Techniques and Applications
- DNA Repair Mechanisms
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Radiation Therapy and Dosimetry
- RNA regulation and disease
- Mycobacterium research and diagnosis
- CRISPR and Genetic Engineering
- Xenotransplantation and immune response
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Chromatin Remodeling and Cancer
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- Ocular Oncology and Treatments
- Tissue Engineering and Regenerative Medicine
Boston University
2020-2025
Johns Hopkins University
2014-2024
Boston Medical Center
2022-2024
Johns Hopkins Medicine
2013-2024
Sidney Kimmel Comprehensive Cancer Center
2011-2022
University School
2021-2022
Cancer Research Center
2010-2020
University of Baltimore
2010-2020
Sidney Kimmel Cancer Center
2012-2018
University Health Network
2017
The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres other genomic sites. Because inactivating mutations of these genes are common human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status tumors. We found that 61% PanNETs displayed abnormal characteristic a telomerase-independent maintenance mechanism termed ALT (alternative lengthening telomeres). All exhibiting had or loss nuclear protein. also correlate with central nervous...
// Yuchen Jiao 1,* , Patrick J. Killela 2,* Zachary Reitman B. Ahmed Rasheed 2 Christopher M. Heaphy 1 Roeland F. de Wilde Fausto Rodriguez Sergio Rosemberg 3 Sueli Mieko Oba-Shinjo Suely Kazue Nagahashi Marie Chetan Bettegowda Nishant Agrawal Eric Lipp Pirozzi Giselle Y. Lopez Yiping He Henry S. Friedman Allan H. Gregory Riggins Matthias Holdhoff 1,4 Peter Burger Roger E. McLendon Darell D. Bigner Bert Vogelstein Alan K. Meeker Kenneth W. Kinzler Nickolas Papadopoulos Luis A. Diaz Jr Hai...
Recent controversies surrounding prostate cancer overtreatment emphasize the critical need to delineate molecular features associated with progression lethal metastatic disease. Here, we have used whole-genome sequencing and pathological analyses characterize cell clone in a patient who died of cancer. We tracked evolution from primary metastases through samples collected during disease at time death. Surprisingly, these revealed that arose small, relatively low-grade focus tumor, not bulk,...
Objective Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in (NETs) from other sites...
Biallelic inactivation of cancer susceptibility gene BRCA1 leads to breast and ovarian carcinogenesis. Paradoxically, deficiency in mice results early embryonic lethality, similarly, lack human cells is thought result cellular lethality view 's essential function. To survive homozygous during tumorigenesis, precancerous must accumulate additional genetic alterations, such as p53 mutations, but this requirement for an extra “hit” contradicts the two-hit theory accelerated carcinogenesis...
Purpose: Alternative lengthening of telomeres (ALT), a telomerase-independent telomere maintenance mechanism, is strongly associated with ATRX and DAXX alterations occurs frequently in pancreatic neuroendocrine tumors (PanNET).Experimental Design: In Korean cohort 269 surgically resected primary PanNETs 19 sporadic microadenomas, ALT status nuclear protein expression were assessed compared clinicopathologic factors.Results: PanNETs, or loss ATRX/DAXX was observed 20.8% 19.3%, respectively,...
A new evaluation of previously published data suggested to us that the accumulation mutations might slow, rather than increase, as individuals age. To explain this unexpected finding, we hypothesized normal stem cell division rates decrease test hypothesis, evaluated in epithelium human colonic, duodenal, esophageal, and posterior ethmoid sinonasal tissues. In all 4 tissues, there was a significant with contrast, did not colon aged mice, only small decreases were observed their intestine or...
Introduction: Recent studies suggest that in addition to factors such as treatment side effects, suicide, and poor health habits, people with schizophrenia may have an increased risk of diabetes prior antipsychotic treatment. Diabetes is associated pulse pressure (PP) a shortened telomere. We tested the hypothesis treatment, related disorders are telomere, well PP. Methods: Telomere content (which highly correlated telomere length) PP were measured newly diagnosed, antipsychotic-naive...
Abstract Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins human breast tumors. The extent, composition and biological significance this are only partially understood, molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability microenvironment supports tumor initiation progression. We demonstrate by microarray, qRT‐PCR immunohistochemistry...
Recent large-scale prospective studies suggest that long telomeres are associated with an increase cancer risk, counter to conventional wisdom.To further clarify the association between leukocyte telomere length (LTL) and prostate cancer, assess genetic variability in relation both LTL we performed a nested case-control study (922 cases 935 controls). The participants provided blood 1993-1995 were followed through August 2004 (prostate incidence) or until 28 February 2013 (lethal fatal...
Current prognostic indicators are imperfect predictors of outcome in men with clinically localized prostate cancer. Thus, tissue-based markers urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability such is a hallmark metastatic lesions, we hypothesized alterations telomere length the primary cancer would predict risk progression metastasis death. To test this hypothesis, conducted prospective cohort study 596...
Abstract Recent studies suggest that the telomere maintenance mechanism known as alternative lengthening of telomeres ( ALT ) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high‐grade astrocytomas (32 pediatric glioblastomas, 65 adult 19 anaplastic astrocytomas) status using tissue microarrays to identify associations molecular phenotypic features. Immunohistochemistry was performed antibodies against , DAXX...
Objective: The aim of this study was to investigate the key molecular alterations in small primary pancreatic neuroendocrine tumors (PanNETs) associated with development liver metastases. Background: Well-differentiated PanNETs size are typically indolent; however, a limited subset metastasize liver. Methods: A total 87 (<3 cm), including 32 metastatic cases and 55 nonmetastatic after 5-year follow-up, were immunolabeled for DAXX/ATRX analyzed alternative lengthening telomeres (ALT) by...
Abstract Anaplasia may be identified in a subset of tumors with presumed pilocytic astrocytoma ( PA ) component or piloid features, which associated aggressive behavior, but the biologic basis this change remains unclear. Fifty‐seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3–75) were included. A clinical diagnosis NF 1 was present 8 (22%). Alternative lengthening telomeres ALT assessed by telomere‐specific FISH and/or CISH . combination immunohistochemistry, DNA...
Cancers must maintain their telomeres at lengths sufficient for cell survival. In several cancer subtypes, a recombination-like mechanism termed alternative lengthening of (ALT), is frequently used telomere length maintenance. utilizing ALT often have lost functional ATRX, chromatin remodeling protein, through mutation or deletion, thereby strongly implicating ATRX as an suppressor. Herein, we generated knockouts in four telomerase-positive, ALT-negative human glioma lines: MOG-G-UVW, SF188,...
Abstract Cancer arises from an accumulation of mutations that promote the selection cells with progressively malignant phenotypes. Previous studies have shown genomic instability, a hallmark cancer cells, is driving force in this process. In present study, two markers telomere DNA content and allelic imbalance, were examined independent cohorts mammary carcinomas. Altered telomeres unbalanced loci both tumors surrounding histologically normal tissues at distances least 1 cm visible tumor...