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1.
Exp Neurol ; 376: 114779, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38621449

ABSTRACT

Neural stem cells have exhibited efficacy in pre-clinical models of spinal cord injury (SCI) and are on a translational path to human testing. We recently reported that neural stem cells must be driven to a spinal cord fate to optimize host axonal regeneration into sites of implantation in the injured spinal cord, where they subsequently form neural relays across the lesion that support significant functional improvement. We also reported methods of deriving and culturing human spinal cord neural stem cells derived from embryonic stem cells that can be sustained over serial high passage numbers in vitro, providing a potentially optimized cell source for human clinical trials. We now report further optimization of methods for deriving and sustaining cultures of human spinal cord neural stem cell lines that result in improved karyotypic stability while retaining anatomical efficacy in vivo. This development improves prospects for safe human translation.


Subject(s)
Cell Differentiation , Neural Stem Cells , Spinal Cord Injuries , Spinal Cord , Humans , Neural Stem Cells/cytology , Spinal Cord/cytology , Animals , Spinal Cord Injuries/therapy , Cell Differentiation/physiology , Cell Culture Techniques/methods , Cells, Cultured , Mice , Stem Cell Transplantation/methods
2.
JAMA Oncol ; 10(5): 575-582, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38451491

ABSTRACT

Importance: Patients with interstitial lung disease (ILD) and early-stage non-small cell lung cancer (NSCLC) have been reported to be at high risk of toxic effects after stereotactic ablative radiotherapy (SABR), but for many patients, there are limited alternative treatment options. Objective: To prospectively assess the benefits and toxic effects of SABR in this patient population. Design, Setting, and Participants: This prospective cohort study was conducted at 6 academic radiation oncology institutions, 5 in Canada and 1 in Scotland, with accrual between March 7, 2019, and January 12, 2022. Patients aged 18 years or older with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgical resection were enrolled. Intervention: Patients were treated with SABR to a dose of 50 Gy in 5 fractions every other day. Main Outcomes and Measures: The study prespecified that SABR would be considered worthwhile if median overall survival-the primary end point-was longer than 1 year, with a grade 3 to 4 risk of toxic effects less than 35% and a grade 5 risk of toxic effects less than 15%. Secondary end points included toxic effects, progression-free survival (PFS), local control (LC), quality-of-life outcomes, and changes in pulmonary function. Intention-to-treat analysis was conducted. Results: Thirty-nine patients enrolled and received SABR. Median age was 78 (IQR, 67-83) years and 59% (n = 23) were male. At baseline, 70% (26 of 37) of patients reported dyspnea, median forced expiratory volume in first second of expiration was 80% (IQR, 66%-90%) predicted, median forced vital capacity was 84% (IQR, 69%-94%) predicted, and median diffusion capacity of the lung for carbon monoxide was 49% (IQR, 38%-61%) predicted. Median follow-up was 19 (IQR, 14-25) months. Overall survival at 1 year was 79% (95%, CI 62%-89%; P < .001 vs the unacceptable rate), and median overall survival was 25 months (95% CI, 14 months to not reached). Median PFS was 19 months (95% CI, 13-28 months), and 2-year LC was 92% (95% CI, 69%-98%). Adverse event rates (highest grade per patient) were grade 1 to 2: n = 12 (31%), grade 3: n = 4 (10%), grade 4: n = 0, and grade 5: n = 3 (7.7%, all due to respiratory deterioration). Conclusions and Relevance: In this trial, use of SABR in patients with fibrotic ILD met the prespecified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT03485378.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Diseases, Interstitial , Lung Neoplasms , Radiosurgery , Humans , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Lung Diseases, Interstitial/etiology , Male , Lung Neoplasms/radiotherapy , Lung Neoplasms/pathology , Female , Radiosurgery/adverse effects , Radiosurgery/methods , Aged , Prospective Studies , Middle Aged , Aged, 80 and over , Quality of Life , Canada
3.
Rev. Inst. Med. Trop. Säo Paulo ; 23(3): 97-101, 1981.
Article in English | LILACS | ID: lil-3073

ABSTRACT

Antigeno soluvel de ovo e fitohemaglutinina foram usados para medir a resposta imunologica celular dos pacientes com esquistossomose mansonica atraves do teste de transformacao linfoblastica. Antigeno soluvel de ovo mostrou resposta maior nos casos com hepatosplenomegalia quando comparados com as formas intestinais simples, as respostas mais altas sendo reencontradas nos grupos etarios mais jovens. Fitohemaglutinina mostrou resposta menor nos casos de esquistossomose intestinal simples e resposta maior nos grupos etarios de media idade. Esses resultados corroboram a importancia da resposta imunologica de tipo celular do hospedeiro nas varias manifestacoes da esquistossomose


Subject(s)
Immunity, Cellular , Schistosomiasis , Lymphocyte Activation
4.
Bull. W.H.O. (Print) ; 5(1): 1-71, 1952.
Article in English | WHO IRIS | ID: who-266208
5.
Geneva; World Health Organization; 1952.
Monography in English, French | WHO IRIS | ID: who-40717

Subject(s)
Kwashiorkor , Africa
6.
Genève; Organisation mondiale de la Santé; 1952.
Monography in English, French | WHO IRIS | ID: who-36890

Subject(s)
Kwashiorkor , Africa
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