Guan M.,Beckman Research Institute |
Fousek K.,Beckman Research Institute |
Jiang C.,Beckman Research Institute |
Guo S.,Beckman Research Institute |
And 4 more authors.
Clinical Cancer Research | Year: 2011
Purpose: We previously reported that nelfinavir (NFV) induces G1 cell-cycle block and apoptosis selectively in liposarcoma cell lines due to increased SREBP-1 (sterol regulatory element binding protein-1) expression in the absence of increased transcription. We postulate that NFV interferes with regulated intramembrane proteolysis of SREBP-1 and ATF6 (activating transcription factor 6). Experimental Design: Time-lapse, confocal microscopic studies show that NFV inhibits the nuclear translocation of full-length SREBP-1-EGFP and ATF6-EGFP fusion proteins. siRNA-mediated knockdown of site-1 protease (S1P) and/or site-2 protease (S2P) leads to inhibition of SREBP-1 intracellular trafficking to the nucleus and reduces liposarcoma cell proliferation. Treatment of LiSa-2 liposarcoma cells with 3,4- dichloroisocoumarin, a serine protease inhibitor of S1P, did not affect SREBP-1 processing. In contrast, 1,10-phenanthroline, an S2P-specific inhibitor, reproduces the molecular and biological phenotypes observed in NFV-treated cells, which implicates S2P as a target of NFV. In vivo evaluation of NFV in a murine liposarcoma xenograft model leads to inhibition of tumor growth without significant toxicity. Results: NFV-induced upregulation of SREBP-1 and ATF6 results from inhibition of S2P, which together with S1P mediates regulated intramembrane proteolysis from their precursor to their transcriptionally active forms. The resulting endoplasmic reticulum (ER) stress and concurrent inhibition of the unfolded protein response induce caspase-mediated apoptosis. Conclusions: These results provide new insight into the mechanism of NFV-mediated induction of ER stress and cell death in liposarcomas and are the first to report targeting S2P for cancer therapy. ©2011 AACR.
Koczywas M.,Medical Oncology and Therapeutics Research |
Freeman B.,Supportive Care Medicine |
Zachariah F.,Supportive Care Medicine |
Uman G.,Vital Research LLC
Cancer | Year: 2015
BACKGROUND Family caregivers (FCGs) experience significant deteriorations in quality of life while caring for patients with lung cancer. In this study, the authors tested the effectiveness of an interdisciplinary palliative care intervention for FCGs of patients diagnosed with stage I through IV nonsmall cell lung cancer. METHODS FCGs who were identified by patients as their primary caregivers were enrolled in a prospective, quasi-experimental study in which the usual care group was accrued first followed by the intervention group. FCGs in the intervention group were presented at interdisciplinary care meetings, and they also received 4 educational sessions organized in the physical, psychological, social, and spiritual domains. The sessions included self-care plans to support the FCG's own needs. Caregiver burden, caregiving skills preparedness, psychological distress, and FCG quality of life were assessed at baseline and after 12 weeks using validated measures. RESULTS In total, 366 FCGs were included in the primary analysis. FCGs who received the interdisciplinary palliative care intervention had significantly better scores for social well being (5.84 vs 6.86; P <.001) and had lower psychological distress scores (4.61 vs 4.20; P =.010) at 12 weeks compared with FCGs in the usual care group. FCGs in the intervention group also had significantly less caregiver burden compared with FCGs in the usual care group (P =.008). CONCLUSIONS An interdisciplinary approach to palliative care in lung cancer resulted in statistically significant improvements in FCG's social well being and psychological distress and in less caregiver burden. © 2015 American Cancer Society.
Koczywas M.,Medical Oncology and Therapeutics Research |
Williams A.C.,Nursing Research and Education |
Cristea M.,Medical Oncology and Therapeutics Research |
Reckamp K.,Medical Oncology and Therapeutics Research |
And 4 more authors.
Annals of Surgical Oncology | Year: 2013
Background: Emerging evidence supports the integration of palliative care concurrently with disease-focused care in patients with serious illnesses, such as lung cancer. This paper describes how longitudinal changes in physical function, symptom burden, and QOL of patients with early-stage non-small cell lung cancer (NSCLC) informed the development of an interdisciplinary, tailored palliative care intervention. Methods: Patients with early stage (I-IIIB) NSCLC were accrued into the usual care phase (Phase 1) of an NCI-funded Program Project Grant. Baseline and longitudinal (up to 52 weeks post-accrual) physical function, symptoms, and QOL were assessed in the thoracic ambulatory clinics of one NCI-designated Comprehensive Cancer Center. Outcome measures included geriatric assessments, psychological distress, symptoms, and QOL. The association between disease stage (I-II vs. III) and longitudinal changes in these domains was evaluated. Results: A total of 103 patients were accrued. Stage I-II patients were significantly more likely to complete the study (p = 0.005). The stages (I-II vs. III) were equivalent at baseline on all demographic variables, clinical, and functional status. Physical function fluctuated longitudinally and was higher at 6 and 24 weeks than at baseline and 12 weeks. There was a longitudinal decrease in total number of symptoms (p < 0.001). Physical and social/family QOL fluctuated longitudinally (p < 0.001 and p = 0.016, respectively). Conclusions: Patients with early-stage NSCLC report a significant longitudinal decrease in physical QOL, and fluctuations in objective and subjective measures of physical function over time were observed regardless of disease stage category. An interdisciplinary palliative care intervention is currently being tested to decrease symptom burden and improve QOL. © 2012 Society of Surgical Oncology.
Borneman T.,Nursing Research and Education |
Koczywas M.,Medical Oncology and Therapeutics Research |
Sun V.,Nursing Research and Education |
Piper B.F.,University of Arizona |
And 4 more authors.
Journal of Palliative Medicine | Year: 2011
Background: Pain and fatigue are recognized as critical symptoms that impact quality of life (QOL) in cancer, particularly in palliative care settings. Barriers to pain and fatigue relief have been classified into three categories: patient, professional, and system barriers. The overall objective of this study was to test the effects of a clinical intervention on reducing barriers to pain and fatigue management in oncology. Methods: This longitudinal, three-group, quasi-experimental study was conducted in three phases: phase 1 (usual care), phase 2 (intervention), and phase 3 (dissemination). A sample of 280 patients with breast, lung, colon, or prostate cancers, stage III and IV disease (80%), and a pain and/or fatigue of 4 or more (moderate to severe) were recruited. The intervention group received four educational sessions on pain/fatigue assessment and management, whereas the control group received usual care. Pain and fatigue barriers and patient knowledge were measured at baseline, 1 month, and 3 months post-accrual for all phases. A 3 × 2 repeated measures statistical design was utilized to derive a priori tests of immediate effects (baseline to 1 month) and sustained effects (baseline or 1 month to 3 months) for each major outcome variable, subscale, and/or scale score. Results: There were significant immediate and sustained effects of the intervention on pain and fatigue barriers as well as knowledge. Measurable improvements in QOL were found in physical and psychological well-being only. Conclusion: A clinical intervention was effective in reducing patient barriers to pain and fatigue management, increasing patient knowledge regarding pain and fatigue, and is feasible and acceptable to patients. © Copyright 2011, Mary Ann Liebert, Inc.
Koczywas M.,Medical Oncology and Therapeutics Research |
Cristea M.,Medical Oncology and Therapeutics Research |
Thomas J.,City of Hope Nursing Research and Education |
McCarty C.,Glendale Memorial Hospital and Health Center |
And 5 more authors.
Clinical Lung Cancer | Year: 2013
Objective Challenges and barriers continue to hinder the integration of palliative care models into comprehensive, ambulatory oncology care. This article aims to describe how symptoms, distress, and quality of life (QOL) data from the usual care phase of a National Cancer Institute-supported Program Project informed the development of an interdisciplinary, tailored palliative care intervention for patients with metastatic non-small-cell lung cancer (NSCLC). Methods Patients receiving usual care for metastatic NSCLC were recruited into this prospective longitudinal study over a 1-year period. A total of 130 patients with stage IV NSCLC were accrued, and 114 patients had evaluable data. Research nurses assisted patients in completing the clinical section of the data forms, and patients completed surveys and self-reports at baseline and 6, 12, and 24 weeks. Results Patients ranged in age from 40 to 84 years, and 61% were Caucasian non-Hispanic. Sixty-six former (N = 59) and current smokers had an average of 38 pack-year history of smoking. The Karnofsky Performance Status, Instrumental Activities of Daily Living, and Cognitive scores deteriorated significantly (P =.001,.009, and.042, respectively). Social Activity was stable, whereas Social Support increased significantly. Overall symptom distress score and Total symptom score both significantly increased at 24 weeks (P =.003 and.017, respectively). Physical Well-Being decreased significantly (P =.036), whereas the Functional Assessment of Cancer Therapy-Lung, Functional Assessment of Chronic Illness Therapy-Spirituality Subscale, and Distress scores remained statistically stable over time. Conclusions Patients with metastatic NSCLC continue to experience high symptom burden and diminished physical well-being over time while receiving cancer treatments. An interdisciplinary palliative care intervention is currently being tested to improve symptom burden and overall QOL. © 2013 Elsevier Inc. All rights reserved.
Motzer R.J.,Sloan Kettering Cancer Center |
Escudier B.,CNRS Gustave Roussy Institute |
Oudard S.,Georges Pompidou Hospital |
Hutson T.E.,Us Oncology Baylor Sammons Cancer Center |
And 8 more authors.
Cancer | Year: 2010
BACKGROUND: A phase 3 trial demonstrated superiority at interim analysis for everolimus over placebo in patients with metastatic renal cell carcinoma (mRCC) progressing on vascular endothelial growth factor receptor-tyrosine kinase inhibitors. Final results and analysis of prognostic factors are reported. METHODS: Patients with mRCC (N = 416) were randomized (2:1) to everolimus 10 mg/d (n = 277) or placebo (n = 139) plus best supportive care. Progression-free survival (PFS) and safety were assessed to the end of double-blind treatment. Mature overall survival (OS) data were analyzed, and prognostic factors for survival were investigated by multivariate analyses. A rank-preserving structural failure time model estimated the effect on OS, correcting for crossover from placebo to everolimus. RESULTS: The median PFS was 4.9 months (everolimus) versus 1.9 months (placebo) (hazard ratio [HR], 0.33; P < .001) by independent central review and 5.5 months (everolimus) versus 1.9 months (placebo) (HR, 0.32; P < .001) by investigators. Serious adverse events with everolimus, independent of causality, in ≥5% of patients included infections (all types, 10%), dyspnea (7%), and fatigue (5%). The median OS was 14.8 months (everolimus) versus 14.4 months (placebo) (HR, 0.87; P = .162), with 80% of patients in the placebo arm crossed over to everolimus. By the rank-preserving structural failure time model, the survival corrected for crossover was 1.9-fold longer (95% confidence interval, 0.5-8.5) with everolimus compared with placebo only. Independent prognostic factors for shorter OS in the study included low performance status, high corrected calcium, low hemoglobin, and prior sunitinib (P < .01). CONCLUSIONS: These results established the efficacy and safety of everolimus in patients with mRCC after progression on sunitinib and/or sorafenib. © 2010 American Cancer Society.Patients:416 patients (intent-to-treat population), 277 were on Certican and 139 placebo. Certican group: n=383 (277 original patients and 106 were switched from placebo after the end of double-blind [DBP] treatment), 216 males and 61 females, median age 61 years, age range 27-85 years (274 included in the safety population); Karnofsky Performance Status (KPS) 100 (n=78), KPS 90 (n=98), KPS 80 (n=72) and KPS 70 (n=28); Memorial Sloan-Kettering Cancer Center (MSKCC) risk: 81 favorable, 156 intermediate and 40 poor; Prior VEGFR-TKI therapy: 124 sunitinib only, 81 sorafenib only and 72 sunitinib/sorafenib; Other previous therapy: 179 immunotherapy, 37 chemotherapy, 5 hormone therapy and 15 other; 85 prior radiotherapy and 269 prior nephrectomy; Sites of metastasis: 210 lymph node, 203 lung, 102 bone, 92 liver, 140 other, 34 kidney and 17 brain. Placebo group: n=139 (106 were switched to Certican at the end-of DBP), 106 males and 33 females, median age 61 years, age range 27-79 years (137 safety population); KPS 100 (n=41), KPS 90 (n=53), KPS 80 (n=30) and KPS 70 (n=15); MSKCC risk: 39 favorable, 79 intermediate and 21 poor; Prior VEGFR-TKI therapy: 60 Sunitinib only, 43 sorafenib only and 36 sunitinib/sorafenib; Other previous therapy: 93 immunotherapy, 22 chemotherapy, 5 hormone therapy and 4 other; 38 prior radiotherapy and 133 prior nephrectomy; Sites of metastasis: 97 lymph node, 112 lung, 42 bone, 53 liver, 59 other, 20 kidney and 12 brain. Dropouts: Certican group n=202 (37 were due to side effects); placebo group n=133 (2 were due to side effects).TypeofStudy:A study evaluating the safety and efficacy of Certican in patients with metastatic renal cell carcinoma (mRCC) who progressed on vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) therapy. A prospective, randomized, double-blind, placebo-controlled, international, multicenter, phase 3 study, and open-label for those who progressed (those on placebo were offered Certican). The RECORD-1 (Renal Cell cancer treatment with Oral RAD001 given Daily) trial. NCT00410124.DosageDuration:10 mg daily orally. Median duration was 141 (range, 19-451 days).Results:At the end of the DBP phase, 75 (27.1%) patients remained on Certican and 6 (4.3%) on placebo. At least 1 dose reduction occurred in 7% and 1% of Certican and placebo patients, respectively. At least 1 treatment interruption occurred in 38% and 11% of Certican and placebo patients, respectively. Interruptions were due to AEs in 35% and 9%, and laboratory test abnormalities in 3% and 2% in the Certican and placebo groups, respectively. After review of all respiratory AEs, 37 (14%) patients had noninfectious pneumonitis (9 grade [Gr] 1, 18 Gr 2, 10 Gr 3). Median time to onset of pneumonitis was 108 days (24-257 days). The risk of infection due to Certican was 1.2-fold to that of placebo. During DBP period, 4 patients died (3 due to infection-related: Candida pneumonia/sepsis with acute respiratory distress syndrome, presumed bacterial sepsis and recurrent bronchopulmonary aspergillosis; and 1 acute respiratory failure with disease progression). Median PFS was 4.9 months with Certican and 1.9 months with placebo. The probability of remaining progression free 10 months after onset of treatment was 25% in Certican. Investigator-assessed data revealed a median PFS of 5.5 months with Certican vs. 1.9 months with placebo. Before ending the DBP treatment, 106 (76.2%) placebo patients progressed and were switched to Certican. Median PFS after switch was 5.1 months. SD was achieved in 185 (66.8%) Certican patients vs. 45 (32.4%) placebo patients. No CRs were noted. The PR rate was 1.8% (n=5) with Certican and 0% placebo. Decreases in tumor volume were noted in 47% and 10% of Certican and placebo patients, respectively. Improved outcome was noted with Certican over placebo. Median PFS for Certican vs. placebo according to prior VEGFR-TKI were: prior sunitinib (n=184), 3.9 vs. 1.8 months; prior sorafenib (n=124), 5.9 vs. 2.8 months; and prior sunitinib/sorafenib (n=108), 4 vs. 1.8 months. Median OS was 14.8 months in Certican vs. 14.4 months in placebo. The number of prior therapies, 1 (n=89) vs. >1 (n=327), was associated with OS duration (11.6 vs. 16.6 months). The probability of being alive at 12 months for the favorable, intermediate, and poor risk groups was 70%, 56%, and 26%, respectively. In the final multivariate Cox model, risk was significantly increased for patients with an intermediate or poor risk score compared with patients with a favorable risk score. Patients with liver or bone metastases, elevated neutrophils, or prior treatment with sunitinib had decreased PFS and OS, indicating prognostic relevance. Respectively, AEs irrespective of drug relevance in the Certican and placebo groups were: stomatitis (44 vs. 8), infections (37 vs. 18), asthenia (33 vs. 23), fatigue (31 vs. 47), diarrhea (30 vs. 7), cough (30 vs. 16), rash (29 vs. 7), nausea (26 vs. 19), anorexia (25 vs. 14), peripheral edema (25 vs. 8), dyspnea (24 vs. 1), vomiting (20 vs. 12), pyrexia (20 vs. 9), mucosal inflammation (19 vs. 1), headache (19 vs. 9), epistaxis (18 vs. 0), pruritus (13 vs. 7), pneumonitis (14 vs. 0), dry skin (13 vs. 5), dysgeusia (10 vs. 2) and pain in extremity (10 vs. 7); and laboratory abnormalities: hemoglobin decreased (92 vs. 79), lymphocytes decreased (51 vs. 28), platelets decreased (23 vs. 2), neutrophils decreased (14 vs. 4), cholesterol increased (77 vs. 35), triglycerides increased (73 vs. 34), glucose increased (57 vs. 25), creatinine increased (50 vs. 34, phosphate decreased (37 vs. 8), aspartate transaminase increased (25 vs. 7), alanine transaminase increased (21 vs. 4) and bilirubin increased (3 vs. 2).AdverseEffects:An unspecified number of patients had side effects (including grade 3 and 4): stomatitis (including aphthous stomatitis, mouth ulceration, and tongue ulceration), infections (including pneumonia, aspergillosis, candidiasis and sepsis), asthenia, fatigue, diarrhea, cough, rash, nausea, anorexia, peripheral edema, dyspnea, vomiting, pyrexia, mucosal inflammation, headache, epistaxis, pruritus, pneumonitis (interstitial lung disease, lung infiltration, pulmonary alveolar hemorrhage, alveolitis, and pulmonary toxicity), dry skin, dysgeusia and pain in extremity; and laboratory abnormalities: decreased hemoglobin, lymphocytes, platelets and neutrophils (including anemia, leukopenia, lymphopenia, neutropenia, pancytopenia and thrombocytopenia), decreased phosphate and increased cholesterol, triglycerides, glucose increased, creatinine, aspartate transaminase, alanine transaminase and bilirubin; leading to withdrawal in 37 patients (3 and 7 patients with grade 2 and 3 pneumonitis, respectively).AuthorsConclusions:In summary, the benefit and safety of everolimus is established in patients with mRCC after progression on VEGFR-TKI therapy. Previously reported Memorial Sloan-Kettering Cancer Center risk features maintained prognostic value in this new clinical setting. Ongoing and future trials with everolimus include clinical studies in combination with bevacizumab and other targeted agents in the front-line setting and sequencing studies with sunitinib and everolimus "as reported".FreeText:All patients received best supportive care (BSC). Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) progression (stable disease [SD], complete response [CR], partial response [PR]). Patients who progressed were unblinded, and those assigned to placebo were offered open-label Certican. Progression-free survival (PFS), adverse events, objective response rate, overall survival (OS) and quality of life were evaluated. Patient-reported outcomes were assessed using the Functional Assessment of Cancer Therapy-Kidney Symptom Index, Disease Related Symptoms questionnaire administered monthly on Day 1 of treatment cycle and at discontinuation. Functional Assessment of Cancer Therapy-Kidney Symptom Index, Disease Related Symptoms was used. Median duration for placebo treatment was 60 days (range, 21-195 days). Tests: hemoglobin, lymphocytes, platelets, neutrophils, phosphate, cholesterol, triglycerides, glucose, creatinine, aspartate transaminase, alanine transaminase and bilirubin.Indications:383 patients with metastatic renal cell carcinoma (210 lymph node, 203 lung, 102 bone, 92 liver, 34 kidney, 17 brain and 140 other metastases.
Juarez G.,Nursing Research and Education |
Mayorga L.,Supportive Care Medicine |
Hurria A.,Medical Oncology and Therapeutics Research |
Ferrell B.,Nursing Research and Education
Psicooncologia | Year: 2013
Objectives: Nueva Luz is an English and Spanish quality of life (QOL) intervention developed to address the educational needs of Latina breast cancer survivors and provide strategies to assist in their transition into survivorship. Methods: A qualitative approach was used to evaluate the English and Spanish educational intervention (Nueva Luz) content. A purposive sample of eight Latina breast cancer survivors was selected from the group who received the intervention to participate in a digitally recorded interview. Data was analyzed using thematic analysis. Results: Findings provide evidence that the one-on-one tailored approach is a feasible and acceptable method of providing a bilingual psychosocial intervention. The provision of printed bilingual information along with the verbal instruction from a bilingual and culturally competent health care provider can be effective in helping Latina breast cancer survivor's transition successfully into survivorship, improve QOL and contribute to better patient outcomes. Conclusions: The study informs our understanding of the cultural context in patient education content and delivery of psychosocial interventions. The findings may also have relevance for other ethnic minority cancer survivors.
Mortimer J.E.,City of Hope Comprehensive Cancer Center |
Pal S.K.,Medical Oncology and Therapeutics Research
Seminars in Oncology | Year: 2010
Bisphosphonates were the first bone-directed therapies used to treat skeletal complications resulting from malignant bone disease. Reducing the incidence of skeletal complications has significantly improved patient quality of life. Intravenous bisphosphonates also have been evaluated as an adjunct treatment to minimize bone loss from cancer therapy. In these settings, there is a suggested improvement in cancer-associated outcomes, in addition to their bone-protective benefits. Denosumab is a fully human antibody to the receptor activator of nuclear factor-κB ligand. Recently reported data suggest that denosumab is efficacious in decreasing skeletal-related events, but the long-term safety of denosumab remains to be determined. The available data for the approved intravenous bisphosphonates, including zoledronic acid, as well as for other investigational bone-directed therapies is reviewed, with a focus on the incidence and management of treatment-associated side effects. © 2010 Elsevier Inc.
PubMed | Medical Oncology and Therapeutics Research
Type: Journal Article | Journal: Annals of surgical oncology | Year: 2013
Emerging evidence supports the integration of palliative care concurrently with disease-focused care in patients with serious illnesses, such as lung cancer. This paper describes how longitudinal changes in physical function, symptom burden, and QOL of patients with early-stage non-small cell lung cancer (NSCLC) informed the development of an interdisciplinary, tailored palliative care intervention.Patients with early stage (I-IIIB) NSCLC were accrued into the usual care phase (Phase 1) of an NCI-funded Program Project Grant. Baseline and longitudinal (up to 52weeks post-accrual) physical function, symptoms, and QOL were assessed in the thoracic ambulatory clinics of one NCI-designated Comprehensive Cancer Center. Outcome measures included geriatric assessments, psychological distress, symptoms, and QOL. The association between disease stage (I-II vs. III) and longitudinal changes in these domains was evaluated.A total of 103 patients were accrued. Stage I-II patients were significantly more likely to complete the study (p=0.005). The stages (I-II vs. III) were equivalent at baseline on all demographic variables, clinical, and functional status. Physical function fluctuated longitudinally and was higher at 6 and 24weeks than at baseline and 12weeks. There was a longitudinal decrease in total number of symptoms (p<0.001). Physical and social/family QOL fluctuated longitudinally (p<0.001 and p=0.016, respectively).Patients with early-stage NSCLC report a significant longitudinal decrease in physical QOL, and fluctuations in objective and subjective measures of physical function over time were observed regardless of disease stage category. An interdisciplinary palliative care intervention is currently being tested to decrease symptom burden and improve QOL.
PubMed | Medical Oncology, Beckman Research Institute, Cytogenetics, Clinical Immunobiology Correlative Studies Laboratory and 5 more.
Type: | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016
Human neural stem cells (NSCs) are inherently tumor-tropic, making them attractive drug delivery vehicles. Toward this goal, we retrovirally transduced an immortalized, clonal NSC line to stably express cytosine deaminase (HB1.F3.CD.C21; CD-NSCs), which converts the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU).Recurrent high grade glioma patients underwent intracranial administration of CD-NSCs during tumor resection or biopsy. Four days later, patients began taking oral 5-FC every 6 hours for 7 days. Study treatment was given only once. A standard 3+3 dose escalation schema was used to increase doses of CD-NSCs from 10 million to 50 million and 5-FC from 75 to 150 mg/kg/day. Intracerebral microdialysis was performed to measure brain levels of 5-FC and 5-FU. Serial blood samples were obtained to assess systemic drug concentrations as well as to perform immunologic correlative studies.Fifteen patients underwent study treatment. We saw no dose-limiting toxicity (DLT) due to the CD-NSCs. There was 1 DLT (grade 3 transaminitis) possibly related to 5-FC. We did not see development of anti-CD-NSC antibodies and did not detect CD-NSCs or replication competent retrovirus in the systemic circulation. Intracerebral microdialysis revealed that CD-NSCs produced 5-FU locally in the brain in a 5-FC dose-dependent manner. Autopsy data indicate that CD-NSCs migrated to distant tumor sites and were non-tumorigenic.Collectively, our results from this first-in-human study demonstrate initial safety and proof-of-concept regarding the ability of NSCs to target brain tumors and locally produce chemotherapy.