Amanda Termuhlen

University of California, Los Angeles, Los Ángeles, California, United States

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Publications (62)157.23 Total impact

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    ABSTRACT: We report the anti-leukemic potency of a unique biotargeted nanoscale liposomal nanoparticle (LNP) formulation of the spleen tyrosine kinase (SYK) P-site inhibitor C61. C61-loaded LNP were decorated with a murine CD19-specific monoclonal antibody directed against radiation-resistant CD19-receptor positive aggressive B-precursor acute lymphoblastic leukemia (ALL) cells. The biotargeted C61-LNP were more potent than untargeted C61-LNP and consistently caused apoptosis in B-precursor ALL cells. The CD19-directed C61-LNP also destroyed B-precursor ALL xenograft cells and their leukemia-initiating in vivo clonogenic fraction. This unique nanostructural therapeutic modality targeting the SYK-dependent anti-apoptotic blast cell survival machinery shows promise for overcoming the clinical radiochemotherapy resistance of B-precursor ALL cells.
    Integrative Biology 06/2014; 6(8). DOI:10.1039/c4ib00095a · 4.00 Impact Factor
  • American Journal of Hematology 12/2013; 88(12):E3-E3. · 3.48 Impact Factor
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    ABSTRACT: We examined the constitutive function of the Ikaros (IK) transcription factor in blast cells from pediatric B-precursor acute lymphoblastic leukemia (BPL) patients using multiple assay platforms and bioinformatics tools. We found no evidence of diminished IK expression or function for primary cells from high-risk BPL patients including a Philadelphia chromosome (Ph)(+) subset. Relapse clones as well as very aggressive in vivo clonogenic leukemic B-cell precursors isolated from spleens of xenografted NOD/SCID mice that developed overt leukemia after inoculation with primary leukemic cells of patients with BPL invariably and abundantly expressed intact IK protein. These results demonstrate that a lost or diminished IK function is not a characteristic feature of leukemic cells in Ph(+) or Ph(-) high-risk BPL.
    PLoS ONE 11/2013; 8(11):e80732. DOI:10.1371/journal.pone.0080732 · 3.53 Impact Factor
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    ABSTRACT: Reproductive health among cancer survivors is an important quality of life issue. Certain cancer therapies have known fertility risks. There is an existing cohort of adolescents and young adults (AYA) cancer survivors that, seen less frequently in clinical care settings than active patients, are likely not having discussions of fertility and other reproductive health issues. A survivor or healthcare provider can easily assume that the window of opportunity for fertility preservation has passed, however emerging research has shown this may not be the case. Recent data demonstrates a close relationship between fertility and other late effects to conclude that ongoing assessment during survivorship is warranted. Some fertility preservation procedures have also been shown to mitigate common late effects. This review explores the link between late effects from treatment and common comorbidities from infertility, which may exacerbate these late effects. This review also highlights the relevance of fertility discussions in the AYA survivorship population.
    Frontiers in Oncology 10/2013; 3:248. DOI:10.3389/fonc.2013.00248
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    ABSTRACT: Administrative data sets are increasingly being used to describe clinical care in sickle cell disease (SCD). We recently used such an administrative database to look at the frequency of acute chest syndrome (ACS) and the use of transfusion to treat this syndrome in California patients from 2005 to 2010. Our results revealed a surprisingly low rate of transfusion for this life-threatening situation. To validate these results, we compared California OSPHD (Office of Statewide Health Planning and Development) administrative data with medical record review of patients diagnosed with ACS identified by two pediatric and one adult hospital databases during 2009-2010. ACS or a related pulmonary process accounted for one-fifth of the inpatient hospital discharges associated with the diagnosis of SCD between 2005 and 2010. Only 47% of those discharges were associated with a transfusion. However, chart reviews found that hospital databases over-reported visits for ACS. OSHPD underreported transfusions compared to hospital data. The net effect was a markedly higher true rate of transfusion (40.7% vs. 70.2%). These results point out the difficulties in using this administrative data base to describe clinical care for ACS given the variation in clinician recognition of this entity. OSPHD is widely used to inform health care policy in California and contributes to national databases. Our study suggests that using this administrative database to assess clinical care for SCD may lead to inaccurate assumptions about quality of care for SCD patients in California. Future studies on health services in SCD may require a different methodology. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 08/2013; 60(12). DOI:10.1002/pbc.24747 · 2.56 Impact Factor
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    ABSTRACT: The Children's Oncology Group's A5971 trial examined central nervous system (CNS) prophylaxis and early intensification in paediatric patients diagnosed with CNS-negative Stage III and IV lymphoblastic lymphoma. Using a 2 × 2 factorial design, the study randomized patients to Children's Cancer Group (CCG) modified Berlin-Frankfurt-Muenster (BFM) acute lymphoblastic leukaemia (ALL) regimen with intensified intrathecal (IT) methotrexate (MTX) (Arm A1) or an adapted non-Hodgkin lymphoma/BFM-95 therapy with high dose MTX in interim maintenance but no IT-MTX in maintenance (Arm B1). Each cohort was randomized ± intensification (cyclophosphamide/anthracycline) (Arms A2/B2). For the 254 randomized patients, there was no difference in 5-year event-free survival (EFS) for the four arms: Arm A1, 80% [95% confidence interval (CI) 67-89%] and Arm A2, 81% (95% CI 69-89%); Arm B1, 80% (95% CI 68-88%) and Arm B2, 84% (95% CI 72-91%). The cumulative incidence of CNS relapse was 1·2%. Age <10 years and institutional imaging response at 2 weeks was associated with improved outcomes (P < 0·001 and P = 0·014 for overall survival). CNS positive patients (n = 12) did poorly [5-year EFS of 63% (95% CI 29-85%)]. For CNS-negative patients, there was no difference in outcome based on CNS prophylaxis (IT-MTX versus HD-MTX) or with intensification.
    British Journal of Haematology 07/2013; DOI:10.1111/bjh.12460 · 4.96 Impact Factor
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    ABSTRACT: We report preclinical proof of principle for effective treatment of B-precursor acute lymphoblastic leukemia (ALL) by targeting the spleen tyrosine kinase (SYK)-dependent antiapoptotic blast cell survival machinery with a unique nanoscale pharmaceutical composition. This nanoscale liposomal formulation (NLF) contains the pentapeptide mimic 1,4-Bis (9-O dihydroquinidinyl) phthalazine/hydroquinidine 1,4-phathalazinediyl diether (C61) as the first and only selective inhibitor of the substrate binding P-site of SYK. The C61 NLF exhibited a very favorable pharmacokinetic and safety profile in mice, induced apoptosis in primary B-precursor ALL blast cells taken directly from patients as well as in vivo clonogenic ALL xenograft cells, destroyed the in vivo clonogenic fraction of ALL blast cells, and, at nontoxic dose levels, exhibited potent in vivo antileukemic activity against patient-derived ALL cells in xenograft models of aggressive B-precursor ALL. Our findings establish SYK as an attractive molecular target for therapy of B-precursor ALL. Further development of the C61 NLF may provide the foundation for therapeutic innovation against therapy-refractory B-precursor ALL.
    Blood 04/2013; 121(21). DOI:10.1182/blood-2012-11-470633 · 9.78 Impact Factor
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    ABSTRACT: Localized lymphoblastic lymphoma (LL) is rare in pediatric patients. We report the 5-year event-free survival (EFS) and overall survival (OS) for children and adolescents with localized LL treated on a uniform regimen based on Children's Cancer Group (CCG) leukemia therapy (COG A5971). From June 2000 to October 2005, the study enrolled 60 patients >12 months old with Murphy stages I or II LL. Central review confirmed 56 eligible patients. Treatment consisted of 24 months of CCG BFM without day 28 intrathecal methotrexate in maintenance therapy or prophylactic cranial radiation. Most patients had pre-B immunophenotype (75%). At a median follow-up of 5.9 years (range 1.4-9.3 years), the 5-year EFS was 90% [95% confidence interval (CI), 78-96%] and the 5-year OS was 96% (95% CI, 84-99%). Stage (I vs. II), immunophenotype, elevated LDH > institutional normal, or primary site did not impact outcome. Five relapses occurred-none in the CNS and none in patients with pre-T lymphoblastic disease. Patients tolerated treatment well with no toxic deaths. Outcomes of pediatric patients with localized LL treated with 2 years of intensive acute lymphoblastic leukemia (ALL)-type therapy was excellent and is similar to the outcome for standard risk ALL treated less intensively. CNS prophylaxis was adequate with limited intrathecal methotrexate and no radiation. Future studies should identify biologic prognostic factors or biomarkers for pediatric patients with LL, explore less intensive treatment for patients with localized disease, and explore novel immunophenotype directed therapies. Pediatr Blood Cancer 2012; 59: 1229-1233. © 2012 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 12/2012; 59(7):1229-33. DOI:10.1002/pbc.24149 · 2.56 Impact Factor
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    ABSTRACT: MS and endocrine dysfunction(s) are common well-recognized complications after HSCT. We retrospectively analyzed our data on 160 patients with a median age at transplant of five yr (0.3-23), who had been followed for a median of seven yr (range 3-18) at Nationwide Children's Hospital after transplant. Dyslipidemia and MS were seen in 13% and 7.5% patients, respectively, and 58% of these patients were <20 yr of age. Twelve patients met the criteria for diagnosis of MS, but four of these did not meet the International Diabetic Federation or WHO criteria. Variation in the diagnostic criteria for MS leading to underdiagnosis is discussed. Female gonadal failure (27%) and hypothyroidism (21%) were the most common endocrine dysfunctions, followed by short stature and GH deficiency (17%) each. TBI and younger age at HSCT were associated with the highest burden of long-term effects, and female sex was more significantly associated with MS-related dysfunction (p < 0.05). Uniform diagnostic criteria for MS and close follow-up after transplant are important for the early diagnosis and management of these late effects, thereby improving the overall quality of life of these patients.
    Pediatric Transplantation 12/2012; 16(8):872-8. DOI:10.1111/petr.12002 · 1.63 Impact Factor
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    ABSTRACT: Background: Sickle Cell Disease (SCD) affects 100,000 individuals in the United States. Advances in care have resulted in a growing population of adults with SCD. Without a parallel increase in the capacity to care for this group of patients, inequities have emerged in access to quality care and health outcomes. Most adult patients are hospitalized outside of SCD centers. Increased mortality in young adults following transition from pediatrics is often due to Acute Chest Syndrome (ACS), a life-threatening pulmonary process usually requiring blood transfusion. Recognition and appropriate treatment of ACS could represent a key indicator of care and promote wellness for adult SCD patients. Our recent query of the California Office of Statewide Health Planning and Development (OSPHD) database found that one-fifth of the hospital inpatient visits associated with the diagnosis of SCD between 2005 and 2008 were for ACS or a related pulmonary process. Despite NIH standard of care guidelines suggesting that transfusion should be used to treat ACS, we found that only 46% of those visits were associated with a transfusion, implying many patients are not receiving appropriate care. Administrative data allows researchers to access large populations but has not been validated for SCD. In light of recognized concerns regarding the relationship of coded diagnoses in administrative data to final clinical diagnoses, we compared OSHPD visit-level discharge data to three hospital databases. Methods: Hospital billing data from 2009-10 identified patients as having ACS. Equal numbers of cases were reported to OSHPD during the same time period. Primary and all secondary diagnoses were reviewed in administrative data. Chart reviews were conducted of identified cases. Results: Chart review identified a higher number of ACS visits in hospital data in light of cases in which ACS was investigated but not proven. More transfusions were identified in hospital data than OSHPD. The net effect was a lower transfusion rate in OSHPD (52.3% Hospital 1; 12.9% Hospital 2; 22.7% Hospital 3) than actual transfusion rate (77% Hospital 1; 50% Hospital 2; 50% Hospital 3). Conclusions: Administrative data is widely used to inform health policy, with OSPHD in particular widely used in California. However, these results suggest that using administrative data to assess clinical care for SCD may lead to inaccurate assumptions about quality of care, thus leading to continuous disparities in health care services.
    140st APHA Annual Meeting and Exposition 2012; 10/2012
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    ABSTRACT: Reproductive health consistently ranks as one of the most important issues cited by adolescent and young adult (AYA) cancer survivors. Most literature on AYA cancer populations neglects broader reproductive health issues such as unintended pregnancies, contraception use and sexually transmitted infections, which, for cancer patients and survivors with compromised immune systems, can facilitate a multitude of future health problems. Lack of attention coupled with traditional risk-taking behaviors of AYAs poses a significant health risk to patients and survivors, particularly if fertility status is unknown or inaccurately assessed. AYA oncology patients and survivors are vulnerable to reproductive health complications that should be addressed prior to, during and after treatment; however, there are currently no tracking systems or evidence-based guidelines to discuss this subject with patients and survivors. Further research is needed to identify physician practices, AYA preferences and strategies for communication that can pave the way to establishing guidelines to discuss in oncology settings.
    Contraception 10/2012; 88(2). DOI:10.1016/j.contraception.2012.08.041 · 2.93 Impact Factor
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    ABSTRACT: Anti-seizure prophylaxis is routinely utilized during busulfan administration for HSCT. We evaluated the feasibility and efficacy of levetiracetam in children undergoing HSCT. A total of 28 children and young adults received levetiracetam during HSCT and the outcomes and costs were compared to a historical, but similar cohort of 25 patients who had received fosphenytoin. Levetiracetam was well tolerated and was efficacious in preventing seizures. Cost of drug, administration, and monitoring were also similar among the two groups. Due to non-induction of the hepatic cytochrome P450 enzymes, levetiracetam may lead to better dose assurance of busulfan in targeted dose regimens for HSCT.
    Pediatric Blood & Cancer 10/2012; 59(4):762-4. DOI:10.1002/pbc.24126 · 2.56 Impact Factor
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    ABSTRACT: Tacrolimus is routinely administered for GVHD prophylaxis as a 24-h continuous infusion that requires a dedicated i.v. line and thus becomes logistically difficult to administer, especially in young pediatric patients. We investigated the safety and efficacy of twice daily bolus infusions of i.v. tacrolimus in 33 children undergoing hematopoietic stem cell transplantation (HSCT) at our institution. Tacrolimus was started at an initial dose of 0.015 mg/kg i.v. bolus administered as a 2-h infusion and then given at every 12 h to maintain a trough drug level between 5-15 ng/mL. Patients also received short-course MTX (66%) or mycophenolate mofetil (34%) in combination with tacrolimus. No acute infusional toxicities were observed with bolus infusions of i.v. tacrolimus. Nephrotoxicity occurred in 14/33 (42%) patients and 48% developed hypertension (HT). Almost all (94%) patients required magnesium supplements to maintain magnesium (Mg) levels 1.5 mg/dL. In all, 3 (9%) patients developed severe sinusoidal obstruction syndrome (SOS). One patient developed posterior reversible leuko-encephalopathy syndrome (PRES) and one additional patient had tremors. The prevelance of these side-effects was similar to those reported for continuous i.v. administration. In all, 28% of the evaluable patients developed acute GVHDgrade II, though the incidence of severe (grade III-IV) GVHD was only 7%. These results suggest that intermittent bolus i.v. tacrolimus administration is a safe and effective method of GVHD prophylaxis in children.Bone Marrow Transplantation advance online publication, 9 April 2012; doi:10.1038/bmt.2012.59.
    Bone marrow transplantation 04/2012; 47(11). DOI:10.1038/bmt.2012.59 · 3.47 Impact Factor
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    ABSTRACT: Treatment cures over 90% of children with Wilms tumor (WT) who subsequently risk late morbidity and mortality. This study describes the 25-year outcomes of 5-year WT survivors in the Childhood Cancer Survivor Study (CCSS). The CCSS, a multi-institutional retrospective cohort study, assessed WT survivors (N = 1,256), diagnosed 1970-1986, for chronic health conditions, health status, health care utilization, socioeconomic status, subsequent malignant neoplasms (SMNs), and mortality compared to the US population and a sibling cohort (N = 4,023). The cumulative incidence of all and severe chronic health conditions was 65.4% and 24.2% at 25 years. Hazard ratios (HR) were 2.0, 95% confidence interval (CI) 1.8-2.3 for grades 1-4 and 4.7, 95%CI 3.6-6.1 for grades 3 and 4, compared to sibling group. WT survivors reported more adverse general health status than the sibling group (prevalence ratio [PR] 1.7; 95%CI 1.2-2.4), but mental health status, socioeconomic outcome, and health care utilization were similar. The cumulative incidence of SMN was 3.0% (95%CI 1.9-4.0%) and of mortality was 6.1% (95%CI 4.7-7.4%). Radiation exposure increased the likelihood of congestive heart failure (CHF) (no doxorubicin-HR 6.6; 95%CI 1.6-28.3; doxorubicin ≤ 250 mg/m(2) -HR 13.0; 95%CI 1.9-89.7; doxorubicin >250 mg/m(2) -HR 18.3; 95%CI 3.8-88.2), SMN (standardized incidence ratio [SIR] 9.0; 95%CI 3.9-17.7 with and 4.9; 95%CI 1.8-10.6 without doxorubicin) and death. Long-term survivors of WT treated from 1970 to 1986 are at increased risk of treatment related morbidity and mortality 25 years from diagnosis.
    Pediatric Blood & Cancer 12/2011; 57(7):1210-6. DOI:10.1002/pbc.23090 · 2.56 Impact Factor
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    ABSTRACT: This study examined the association between sociodemographic, cancer treatment, and care delivery factors on young adult cancer survivors' confidence in managing their survivorship care. Survivors aged 18-39 years (n = 376) recruited from the LIVESTRONG™ Survivorship Center of Excellence Network sites completed a survey assessing self-reported receipt of survivorship care planning, expectations of their providers, and confidence in managing their survivorship care. Multivariate logistic regression identified characteristics of those reporting low confidence in managing their survivorship care. Mean age was 28 years; mean interval from diagnosis was 9 ± 8 years. Seventy-one percent reported currently attending an oncology survivorship clinic. Regarding survivorship care planning, 33% did not have copies of their cancer-related medical records, 48% did not have a treatment summary, and 55% had not received a survivorship care plan. Seventy percent identified the oncologist as the most important health care provider for decisions regarding test and treatment decisions while 10% reported using a "shared-care model" involving both primary care providers and oncologists. Forty-one percent were classified as having low confidence in managing survivorship care. In multivariate analysis, low confidence was associated with non-white ethnicity and lack of a survivorship care plan (both p < 0.05). Findings suggest that provision of survivorship care plans for young adult cancer survivors can be used to improve confidence in managing survivorship care, particularly for ethnic minorities. Survivors should consider advocating for receipt of a survivorship care plan as it may facilitate confidence as a consumer of survivorship care.
    Journal of Cancer Survivorship 12/2011; 5(4):371-81. DOI:10.1007/s11764-011-0199-1 · 3.29 Impact Factor
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    ABSTRACT: A 10-year-old female with Williams Syndrome (WS) presented with a two-month history of fatigue, weight loss, and bilateral ovarian masses. Histologic, immunophenotypic, and cytogenetic studies confirmed the diagnosis of Burkitt lymphoma (BL). While there is no established association between the two disorders, this is the third case in the literature of Burkitt lymphoma in a patient with Williams Syndrome.
    Case Reports in Medicine 05/2011; 2011:327263. DOI:10.1155/2011/327263
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    ABSTRACT: To determine the frequency of venous thromboembolism (VTE) in the adolescent and young adult oncology population and the effects of age and cancer type on VTE, and to characterize adolescent and young adult oncology admissions at US children's hospitals. We extracted data on oncology patients 15 to 24 years of age who were discharged from 35 hospitals in the Pediatric Hospital Information System (PHIS) between 2001 and 2008. Of 9721 unique patients, VTE occurred in 511 (5.3%). An elevated OR of VTE occurred in patients 18 to 20 and 21 to 24 years of age (OR, 1.65; 95% CI, 1.36-2.00 and OR, 1.67; 95% CI, 1.21-2.32, respectively) compared with that in patients 15 to 17 years old. Patients with leukemia (OR, 5.53; 95% CI, 3.63-8.42) and bone/soft tissue sarcomas (OR, 4.32; 95% CI, 2.80-6.69) had a higher risk of VTE compared with patients with brain tumors. The number of adolescent and young adult oncology admissions to pediatric hospitals increased 31.9%, from 5409 admissions in 2001 to 7134 admissions in 2008. Adolescent and young adult oncology patients, a growing population at pediatric hospitals, experience VTE as a common complication. Pediatricians should implement adolescent and young adult-specific studies to develop a standardized approach to preventing this adverse event.
    The Journal of pediatrics 02/2011; 159(1):133-7. DOI:10.1016/j.jpeds.2011.01.005 · 3.74 Impact Factor
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    ABSTRACT: This prospective study was designed to determine the safety and efficacy of cyclophosphamide, BCNU, and etoposide (CBV) conditioning and autologous peripheral blood stem cell transplant (PBSCT) in children with relapsed or refractory Hodgkin and non-Hodgkin lymphoma (HL and NHL). Patients achieving complete remission (CR) or partial remission (PR) after 2 to 4 courses of reinduction underwent a granulocyte-colony stimulating factor (G-CSF) mobilized PBSC apheresis with a target collection dose of 5 × 10⁶ CD34(+)/kg. Those eligible to proceed received autologous PBSCT after CBV (7200 mg/m², 450-300 mg/m², 2400 mg/m²). Forty-three of 69 patients (30/39 HL, 13/30 NHL) achieved a CR/PR after reinduction. Thirty-eight patients (28 HL, 10 NHL) underwent PBSCT. All initial 6 patients who received BCNU at 450 mg/m² experienced grade III or IV pulmonary toxicity compared to none of the subsequent 32 receiving 300 mg/m² (P < .0001). The probability of overall survival (OS) at 3 years for all patients is 51% and for transplanted patients is 64%. The 3-year event-free survival (EFS) is 38% (45% for HL; 30% NHL). The 3-year EFS in transplanted patients is 66% (65% HL; 70% NHL). Initial duration of remission of ≥12 versus <12 months was associated with a significant increase in OS (3 years OS 70% versus 34%) (P = .003). BCNU at 300 mg/m(2) in a CBV regimen prior to PBSCT is well tolerated in relapsed or refractory pediatric lymphoma patients. A short duration (<12 months) of initial remission is associated with a poorer prognosis. Last, a high percentage of patients achieving a CR/PR after reinduction therapy can be salvaged with CBV and autologlous PBSCT.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2011; 17(2):249-58. DOI:10.1016/j.bbmt.2010.07.002 · 3.35 Impact Factor
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    ABSTRACT: Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in osteosarcoma, and hence, may serve as a therapeutic target. In order to target STAT3, we tested two new STAT3 inhibitors, LLL12 and FLLL32. LLL12 and FLLL32 inhibit STAT3 phosphorylation and STAT3 downstream targets. LLL12 and FLLL32 also inhibit IL-6 induced STAT3 phosphorylation. The inhibition of STAT3 by LLL12 and FLLL32 resulted in the induction of apoptosis, reduction of plating efficiency, and migration in osteosarcoma cells. Furthermore, LLL12 and FLLL32 inhibited SJSA osteosarcoma cells and OS-33 tumor growth in murine xenografts. These results provide evidence that constitutive STAT3 signaling is required for osteosarcoma survival and migration in vitro and tumor growth in vivo. Blocking persistent STAT3 signaling by LLL12 and FLLL32 may be a novel therapeutic approach for osteosarcoma.
    Investigational New Drugs 02/2011; 30(3):916-26. DOI:10.1007/s10637-011-9645-1 · 2.93 Impact Factor

Publication Stats

423 Citations
157.23 Total Impact Points

Institutions

  • 2013
    • University of California, Los Angeles
      • Department of Pediatrics
      Los Ángeles, California, United States
  • 2012–2013
    • University of Southern California
      • Department of Pediatrics
      Los Ángeles, California, United States
  • 2011–2012
    • California State University, Long Beach
      Long Beach, California, United States
  • 2010–2012
    • Nationwide Children's Hospital
      • Center for Childhood Cancer and Blood Diseases
      Columbus, Ohio, United States
  • 2003–2011
    • The Ohio State University
      • Department of Pediatrics
      Columbus, Ohio, United States
  • 2009
    • National Cancer Center, Japan
      Edo, Tōkyō, Japan
  • 2008
    • Columbus Community Hospital, Inc.
      Columbus, Nebraska, United States
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2007
    • Wolfson Childrens Hospital
      Jacksonville, Florida, United States
  • 2006
    • Tehran University of Medical Sciences
      • Hematology-Oncology and Stem Cell Research Center
      Teheran, Tehrān, Iran