ABSTRACT
Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.
ABSTRACT
Two questionnaires were developed for measuring disability due to juvenile rheumatoid arthritis (JRA), one based on patient reports and one on parent reports. These questionnaires were termed the Juvenile Arthritis Functional Assessment Report for Children (JAFAR-C) and for Parents (JAFAR-P). The questionnaires were administered to 72 JRA patients ages 7-18 years and to their parents. Respondents rated the patient's recent ability to perform 23 activities. Patient reports and parent reports were found to correlate highly with each other and with an objective assessment performed by therapists. Questionnaire scores did not correlate significantly with the age of the patient. The JAFAR appears to be a convenient, reliable, and valid measure of disability in patients with JRA.
Subject(s)
Arthritis, Juvenile/physiopathology , Disability Evaluation , Parents , Adolescent , Child , Humans , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
A disability assessment tool, the Juvenile Arthritis Functional Assessment Scale, was developed for, and validated in, patients with juvenile rheumatoid arthritis (JRA). Standards for this 10-item tool were developed using the scores of 63 normal school children as controls and comparing these results with those of 71 age-matched JRA patients (age 7-16 years). The JRA patients scored statistically significantly higher on the scale, which also demonstrated excellent internal and convergent validity and internal reliability. The test is easily administered in 10 minutes by a physical or occupational therapist in a clinical or office setting. This tool represents the first normalized disability assessment tool developed for JRA patients.
