ABSTRACT
Osteosarcoma has a poor prognosis due to chemo-resistance and/or metastases. Increasing evidence shows that long non-coding RNAs (lncRNAs) can play an important role in drug sensitivity and cancer metastasis. Using osteosarcoma cell lines, we identified a positive correlation between the expression of a lncRNA and ANRIL, and resistance to two of the three standard-of-care agents for treating osteosarcoma-cisplatin and doxorubicin. To confirm the potential role of ANRIL in chemosensitivity, we independently inhibited and over-expressed ANRIL in osteosarcoma cell lines followed by treatment with either cisplatin or doxorubicin. Knocking-down ANRIL in SAOS2 resulted in a significant increase in cellular sensitivity to both cisplatin and doxorubicin, while the over-expression of ANRIL in both HOS and U2OS cells led to an increased resistance to both agents. To investigate the clinical significance of ANRIL in osteosarcoma, we assessed ANRIL expression in relation to clinical phenotypes using the osteosarcoma data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset. Higher ANRIL expression was significantly associated with increased rates of metastases at diagnosis and death and was a significant predictor of reduced overall survival rate. Collectively, our results suggest that the lncRNA ANRIL can be a chemosensitivity and prognosis biomarker in osteosarcoma. Furthermore, reducing ANRIL expression may be a therapeutic strategy to overcome current standard-of-care treatment resistance.
Subject(s)
Biomarkers, Tumor/metabolism , Cisplatin/pharmacology , Doxorubicin/pharmacology , Osteosarcoma/drug therapy , Osteosarcoma/metabolism , RNA, Long Noncoding/metabolism , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/genetics , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Cell Line, Tumor , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Osteosarcoma/genetics , Prognosis , RNA, Long Noncoding/geneticsABSTRACT
BACKGROUND: As pharmacy evolves, pharmacists have an increasing role in documentation. Publications examining the actions of other health professionals show that negative perception in written notes translates to patients receiving lower quality of care, resulting in worse health outcomes, suggesting that the use of stigmatizing language towards patients has concerning consequences. OBJECTIVES: To identify the prevalence of stigmatizing language in inpatient pharmacy progress. notes based on patient specific characteristics and diagnoses. METHODS: This retrospective pilot study reviewed inpatient pharmacy progress notes of a Midwestern (United States) tertiary academic institution from May to June 2023. Stigmatizing words and phrases associated with specified disease states were separated into the categories of general language, substance use disorders, and mental health. Notes of patients on internal medicine, family medicine, kidney/pancreas transplant, liver transplant, and gastroenterology services were included. RESULTS: Stigmatizing language was found in 22% (n = 43) of notes. The words "abuse" and "dependence" had the highest prevalence. Patients diagnosed with substance use disorders experienced stigmatizing language at a high rate, exaggerated further if their note lacked a documented diagnosis. CONCLUSIONS: This study demonstrated that stigmatizing language is present in pharmacy documentation. Providing context and resources of the proper documentation to reflect equitable healthcare is crucial for patient care.