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Article: Rhabdomyosarcoma in adolescent and young adult patients: current perspectives.

Egas-Bejar, Daniela / Huh, Winston W

Adolescent health, medicine and therapeutics

2014 Volume 5, Page(s) 115–125

Abstract: Rhabdomyosarcoma (RMS), a malignant tumor of mesenchymal origin, is the third most common extracranial malignant solid tumor in children and adolescents. However, in adults, RMS represents <1% of all solid tumor malignancies. The embryonal and alveolar ... ...

Abstract	Rhabdomyosarcoma (RMS), a malignant tumor of mesenchymal origin, is the third most common extracranial malignant solid tumor in children and adolescents. However, in adults, RMS represents <1% of all solid tumor malignancies. The embryonal and alveolar histologic variants are more commonly seen in pediatric patients, while the pleomorphic variant is rare in children and seen more often in adults. Advances in the research of the embryonal and alveolar variants have improved our understanding of certain genes and biologic pathways that are involved in RMS, but much less is known for the other variants. Multimodality therapy that includes surgery and chemotherapy with or without radiation therapy is the mainstay of treatment for RMS. Improvements in the risk stratification of the pediatric patients based on presurgical (primary tumor site, tumor size, regional lymph node involvement, presence of metastasis) and postsurgical parameters (completeness of resection or presence of residual disease or metastasis) has allowed for the treatment assignment of patients in different studies and therapeutic trials, leading to increases in 5-year survival from 25%-70% over the past 40 years. However, for adult patients, in great part due to rarity of the disease and the lack of consensus on optimal treatment, clinical outcome is still poor. Many factors have been implicated for the differing outcomes between pediatric RMS versus adult RMS, such as the lack of standardized treatment protocols for adult RMS patients and the increased prevalence of advanced presentations. Now that there are increased numbers of survivors, we can appreciate the sequelae from therapy in these patients, such as bone growth abnormalities, endocrinopathies, and infertility. Improvements in risk stratification have led to clinical trials using lower doses of chemotherapy or radiation therapy with the intention of decreasing the incidence of side effects without compromising survival outcome.
Language	English
Publishing date	2014-06-17
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2587456-1
ISSN	1179-318X
ISSN	1179-318X
DOI	10.2147/AHMT.S44582
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Rhabdomyosarcoma in adolescent and young adult patients

Egas-Bejar D / Huh WW

Adolescent Health, Medicine and Therapeutics, Vol 2014, Iss default, Pp 115-

current perspectives

2014 Volume 125

Abstract: Daniela Egas-Bejar, Winston W Huh Division of Pediatrics, The Children’s Cancer Hospital ...

Abstract	Daniela Egas-Bejar, Winston W Huh Division of Pediatrics, The Children’s Cancer Hospital, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Rhabdomyosarcoma (RMS), a malignant tumor of mesenchymal origin, is the third most common extracranial malignant solid tumor in children and adolescents. However, in adults, RMS represents <1% of all solid tumor malignancies. The embryonal and alveolar histologic variants are more commonly seen in pediatric patients, while the pleomorphic variant is rare in children and seen more often in adults. Advances in the research of the embryonal and alveolar variants have improved our understanding of certain genes and biologic pathways that are involved in RMS, but much less is known for the other variants. Multimodality therapy that includes surgery and chemotherapy with or without radiation therapy is the mainstay of treatment for RMS. Improvements in the risk stratification of the pediatric patients based on presurgical (primary tumor site, tumor size, regional lymph node involvement, presence of metastasis) and postsurgical parameters (completeness of resection or presence of residual disease or metastasis) has allowed for the treatment assignment of patients in different studies and therapeutic trials, leading to increases in 5-year survival from 25%–70% over the past 40 years. However, for adult patients, in great part due to rarity of the disease and the lack of consensus on optimal treatment, clinical outcome is still poor. Many factors have been implicated for the differing outcomes between pediatric RMS versus adult RMS, such as the lack of standardized treatment protocols for adult RMS patients and the increased prevalence of advanced presentations. Now that there are increased numbers of survivors, we can appreciate the sequelae from therapy in these patients, such as bone growth abnormalities, endocrinopathies, and infertility. Improvements in risk stratification have led to clinical trials using lower doses of chemotherapy or radiation therapy with the intention of decreasing the incidence of side effects without compromising survival outcome. Keywords: rhabdomyosarcoma, soft-tissue sarcoma, late effects
Keywords	Pediatrics ; RJ1-570 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2014-06-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analysis of redox and apoptotic effects of anthracyclines to delineate a cardioprotective strategy.

Fulbright, Joy Marie / Egas-Bejar, Daniela E / Huh, Winston W / Chandra, Joya

Cancer chemotherapy and pharmacology

2015 Volume 76, Issue 6, Page(s) 1297–1307

Abstract: Purpose: Cardiotoxic side effects of anthracyclines limit their use as effective chemotherapeutics. One mechanistic model of anthracycline-induced cardiotoxicity is attributed to the generation of intracellular reactive oxygen species (ROS). However, ... ...

Abstract	Purpose: Cardiotoxic side effects of anthracyclines limit their use as effective chemotherapeutics. One mechanistic model of anthracycline-induced cardiotoxicity is attributed to the generation of intracellular reactive oxygen species (ROS). However, this theory has been questioned because several cardioprotective strategies have included the use of antioxidants without significant clinical benefit. We sought to determine whether measurement of intracellular reactive oxygen species after anthracycline exposure in vivo and in vitro could provide a means for designing more effective antioxidant-based cardioprotective schemes. Methods: Intracellular levels of ROS were assessed in peripheral blood mononuclear cells from leukemia bearing mice exposed to anthracyclines and in patients receiving anthracyclines. Comparison of cell death induction and ROS levels were also conducted in vitro in cardiomyocyte and leukemia lines. ROS blockade using antioxidants was conducted, and effects on cell death were assessed. Results: Elevated ROS in blood of mice and representative patient samples correlated with cardiomyocyte necrosis and decreased ejection fraction. In vitro, comparison of the cytotoxic effects of anthracyclines in acute leukemia cells and in cardiomyocytes revealed distinct kinetics of cell death induction and dependence upon oxidative stress. Although apoptotic cell death was observed in both acute leukemia cells and cardiomyocytes, the antioxidant N-acetylcysteine protected cardiomyocytes but not acute leukemia cells from anthracycline cytotoxicity. Conclusions: Our findings point toward revisiting the use of NAC as a cardioprotective agent since it does not appear to interfere with the cytotoxic action of anthracyclines. NAC has been evaluated clinically for cardioprotective activity but future trials must ensure that adequate dose, scheduling and incorporation of markers of oxidative stress are included.
MeSH term(s)	Acetylcysteine/pharmacology ; Acute Disease ; Adolescent ; Animals ; Anthracyclines/adverse effects ; Antioxidants/pharmacology ; Apoptosis/drug effects ; Cardiotonic Agents/pharmacology ; Cell Line ; Cell Line, Tumor ; Child, Preschool ; Female ; Heart Diseases/chemically induced ; Heart Diseases/prevention & control ; Humans ; Jurkat Cells ; Leukemia/blood ; Leukemia/drug therapy ; Leukemia/pathology ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Male ; Mice, Inbred BALB C ; Mice, SCID ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Rats ; Reactive Oxygen Species/metabolism
Chemical Substances	Anthracyclines ; Antioxidants ; Cardiotonic Agents ; Reactive Oxygen Species ; Acetylcysteine (WYQ7N0BPYC)
Language	English
Publishing date	2015-12
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	6820-2
ISSN	1432-0843 ; 0344-5704 ; 0943-9404
ISSN (online)	1432-0843
ISSN	0344-5704 ; 0943-9404
DOI	10.1007/s00280-015-2879-4
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Article: Theranostic Profiling for Actionable Aberrations in Advanced High Risk Osteosarcoma with Aggressive Biology Reveals High Molecular Diversity: The Human Fingerprint Hypothesis.

Egas-Bejar, Daniela / Anderson, Pete M / Agarwal, Rishi / Corrales-Medina, Fernando / Devarajan, Eswaran / Huh, Winston W / Brown, Robert E / Subbiah, Vivek

Oncoscience

2014 Volume 1, Issue 2, Page(s) 167–179

Abstract: The survival of patients with advanced osteosarcoma is poor with limited therapeutic options. There is an urgent need for new targeted therapies based on biomarkers. Recently, theranostic molecular profiling services for cancer patients by CLIA-certified ...

Abstract	The survival of patients with advanced osteosarcoma is poor with limited therapeutic options. There is an urgent need for new targeted therapies based on biomarkers. Recently, theranostic molecular profiling services for cancer patients by CLIA-certified commercial companies as well as in-house profiling in academic medical centers have expanded exponentially. We evaluated molecular profiles of patients with advanced osteosarcoma whose tumor tissue had been analyzed by one of the following methods: 1. 182-gene next-generation exome sequencing (Foundation Medicine, Boston, MA), 2. Immunohistochemistry (IHC)/PCR-based panel (CARIS Target Now, Irving, Tx), 3.Comparative genome hybridization (Oncopath, San Antonio, TX). 4. Single-gene PCR assays,
Language	English
Publishing date	2014-07-15
Publishing country	United States
Document type	Journal Article
ISSN	2331-4737
ISSN	2331-4737
DOI	10.18632/oncoscience.21
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Article ; Online: Cerebral sinovenous thrombosis associated with iron deficiency anemia secondary to severe menorrhagia: a case report.

Corrales-Medina, Fernando F / Grant, Leon / Egas-Bejar, Daniela / Valdivia-Ascuna, Zoila / Rodriguez, Nidra / Mancias, Pedro

Journal of child neurology

2014 Volume 29, Issue 9, Page(s) NP62–4

Abstract: Cerebral sinovenous thrombosis is a rare condition presenting with a wide spectrum of nonspecific symptoms that can make early diagnosis difficult. Cerebral sinovenous thrombosis has been associated with various etiologies. Iron deficiency anemia ... ...

Abstract	Cerebral sinovenous thrombosis is a rare condition presenting with a wide spectrum of nonspecific symptoms that can make early diagnosis difficult. Cerebral sinovenous thrombosis has been associated with various etiologies. Iron deficiency anemia associated with cerebral sinovenous thrombosis in teenagers is rare. We present a teenage patient with complete thrombosis of the vein of Galen, straight sinus, and left internal cerebral vein associated with iron deficiency anemia due to severe menorrhagia. Mechanisms that can explain the association between iron deficiency anemia and thrombosis are discussed.
MeSH term(s)	Adolescent ; Anemia, Iron-Deficiency/drug therapy ; Anemia, Iron-Deficiency/etiology ; Brain/pathology ; Female ; Follow-Up Studies ; Humans ; Intracranial Thrombosis/diagnostic imaging ; Intracranial Thrombosis/drug therapy ; Intracranial Thrombosis/etiology ; Magnetic Resonance Imaging, Cine ; Menorrhagia/complications ; Tomography, X-Ray Computed
Language	English
Publishing date	2014-09
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	639288-x
ISSN	1708-8283 ; 0883-0738
ISSN (online)	1708-8283
ISSN	0883-0738
DOI	10.1177/0883073813500715
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: New treatment options for nonmetastatic osteosarcoma

Huh WW / Egas-Bejar D / Anderson PM

Clinical Oncology in Adolescents and Young Adults, Vol 2012, Iss default, Pp 1-

focus on mifamurtide in adolescents

2012 Volume 6

Abstract: Winston W Huh, Daniela Egas-Bejar, Peter M AndersonDivision of Pediatrics, The Children's ...

Abstract	Winston W Huh, Daniela Egas-Bejar, Peter M AndersonDivision of Pediatrics, The Children's Cancer Hospital of the University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: New treatments are needed to improve the clinical outcome for patients with osteosarcoma. Liposomal muramyl tripeptide phosphatidylethanolamine (mifamurtide) is a synthetic peptidoglycan component packaged in multilamellar liposomes. Mifamurtide has been demonstrated to induce recruitment and activation of macrophages and monocytes of the host innate immune system, which leads to antitumoricidal activity. Early clinical trials have demonstrated the safety and tolerability of mifamurtide combined with chemotherapy, and one major study has demonstrated an overall survival benefit in patients with newly diagnosed nonmetastatic osteosarcoma. This review summarizes the mechanism of action, clinical results, and the optimal biologic dose, and raises potential questions for future development of mifamurtide.Keywords: osteosarcoma, childhood cancer, adolescent, sarcoma, immunotherapy, bone
Keywords	Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2012-09-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Clinical characteristics and outcomes of pediatric oncology patients with aggressive biology enrolled in phase I clinical trials designed for adults: the university of Texas MD anderson cancer center experience.

Corrales-Medina, Fernando F / Herzog, Cynthia / Hess, Kenneth / Egas-Bejar, Daniela / Hong, David S / Falchook, Gerald / Anderson, Pete / Nunez, Cesar / Huh, Winston W / Naing, Aung / Tsimberidou, Apostolia M / Wheler, Jennifer / Paul, Sarina Piha / Janku, Filip / Kleinerman, Eugenie S / Kurzrock, Razelle / Subbiah, Vivek

Oncoscience

2014 Volume 1, Issue 7, Page(s) 522–530

Abstract: Background: Children (patients ≤ 18 years of age) are not usually included on pharmaceutical industry sponsored Phase I trials.: Methods: We reviewed the medical records of 40 patients ≤ 18 years treated in ≥ 1 phase I trial at MD Anderson.: ... ...

Abstract	Background: Children (patients ≤ 18 years of age) are not usually included on pharmaceutical industry sponsored Phase I trials. Methods: We reviewed the medical records of 40 patients ≤ 18 years treated in ≥ 1 phase I trial at MD Anderson. Results: The median OS was 8.5 months (95% CI, 5.5-13.2 months). In the multivariate analysis, age ≥15 only predicted increased OS (P = 0.0065), and >3 prior therapies (P = 0.053) predicted decreased OS. The median PFS was 2.8 months (95% CI, 2.3-4.1 months). In the multivariate analysis, independent factors that predicted increased PFS were age ≥15 years (P < 0.001) and prior radiation therapy (P = 0.049); performance status >1 (P < 0.001) and >3 prior therapies (P = 0.002) predicted decreased PFS. RMH score ≥ 2 and MDACC score ≥ 3 were associated with decreased median OS (P = 0.029 and P = 0.031 respectively). Conclusions: It is feasible to conduct phase I studies in pediatric patients based on adult protocols. In the era of targeted therapy more trials should allow pediatric patients earlier in the drug development especially if deemed safe in adults in early phase trials. Translational relevance: Most pharmaceutical industry sponsored trials exclude patients less than 18 years in phase I clinical trials. Even in the era of targeted therapy pediatric patients usually have to wait for most phases of trials to be completed in adults before being allowed to enroll in clinical trials of new therapies, even in the advanced metastatic and relapsed setting. Some investigator initiated phase 1 trials of combinations of US FDA approved agents allow patients less than 18 years. We report the preliminary analyses of the outcomes of pediatric patients enrolled in phase I studies initially designed for adults, but allowing for enrollment of patients under 18.
Language	English
Publishing date	2014-12-06
Publishing country	United States
Document type	Journal Article
ISSN	2331-4737
ISSN	2331-4737
DOI	10.18632/oncoscience.68
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Analysis of CFTR gene mutations and cystic fibrosis incidence in the Ecuadorian population.

Valle, Edison Patricio / Burgos, Ramiro Israel / Valle, José Rubén / Egas Béjar, Daniela / Ruiz-Cabezas, Juan-Carlos

Investigacion clinica

2007 Volume 48, Issue 1, Page(s) 91–98

Abstract: Ecuador is one of the Latin American countries where cystic fibrosis has not been thoroughly studied. The goal of this study was to establish the incidence of this specific pathology and the incidence of the 29 most common European CF mutations in ... ...

Abstract	Ecuador is one of the Latin American countries where cystic fibrosis has not been thoroughly studied. The goal of this study was to establish the incidence of this specific pathology and the incidence of the 29 most common European CF mutations in Ecuador's population. We performed a prospective-descriptive study with the intention of including patients registered at the Ecuadorian Cystic Fibrosis Foundation as well as the main pediatric hospitals in Ecuador. The inclusion criteria were clinical manifestations of cystic fibrosis plus two positive pilocarpine iontophoresis sweat tests (CI >60 mEq/L). We tested F508del mutation by heteroduplex method and then, we confirmed these results and searched for other 28 frequent European-mutations aside from F508del by a reverse dot blot technique (INNO-LiPA CFTR 29 + Tn). Sixty two unrelated patients were included. Both heteroduplex and reverse dot blot methods identified 53.22% of all mutations. The estimated Ecuadorian cystic fibrosis incidence was 1:11,252. The mutations found and their incidence were F508del (37.1%), G85E (8.9%), G542X (2.4%), N1303K (2.4%), G551D (1.6%) and R334W (0.8%). The incidence of cystic fibrosis in Ecuador is closely similar to other Latin American countries where there is a large "mestizo" population. We are reporting one of the highest incidences of G85E in the world.
MeSH term(s)	Adolescent ; Adult ; Child ; Child, Preschool ; Cystic Fibrosis/epidemiology ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; DNA Mutational Analysis ; Ecuador/epidemiology ; European Continental Ancestry Group/genetics ; Female ; Gene Frequency ; Genotype ; Hospitals, Pediatric/statistics & numerical data ; Humans ; Incidence ; Indians, South American/genetics ; Infant ; Infant, Newborn ; Male ; Mutation ; Mutation, Missense ; Point Mutation ; Prospective Studies ; Registries ; Sequence Deletion ; Spain/ethnology ; Sweat/chemistry
Chemical Substances	CFTR protein, human ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2007-03
Publishing country	Venezuela
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	969078-5
ISSN	0535-5133
ISSN	0535-5133
Database	MEDical Literature Analysis and Retrieval System OnLINE

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