Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment resistance remains the primary obstacle to the successful treatment of NSCLC. Although drug resistance mechanisms have been studied extensively in NSCLC, the regulation of these mechanisms has not been completely understood. Recently, increasing numbers of microRNAs (miRNAs) are implicated in EGFR-TKI resistance, indicating that miRNAs may serve as novel targets and may hold promise as predictive biomarkers for anti-EGFR therapy. MicroRNA-506 (miR-506) has been identified as a tumor suppressor in many cancers, including lung cancer; however, the role of miR-506 in lung cancer chemoresistance has not yet been addressed. Here we report that miR-506-3p expression was markedly reduced in erlotinib-resistant (ER) cells. We identified Sonic Hedgehog (SHH) as a novel target of miR-506-3p, aberrantly activated in ER cells. The ectopic overexpression of miR-506-3p in ER cells downregulates SHH signaling, increases E-cadherin expression, and inhibits the expression of vimentin, thus counteracting the epithelial–mesenchymal transition (EMT)-mediated chemoresistance. Our results advanced our understanding of the molecular mechanisms underlying EGFR-TKI resistance and indicated that the miR-506/SHH axis might represent a novel therapeutic target for future EGFR mutated lung cancer treatment.
1 May 2013 in Infectious Diseases in Clinical Practice
Spinal tuberculosis (TB), a destructive form of extrapulmonary TB, is uncommon in the United States. It is more common among immigrants from TB-endemic countries. Typically, the infection spreads to the vertebrae from a primary site elsewhere. Spinal TB commonly presents with an insidious onset of nonspecific back pain and can be the first presenting symptom of underlying TB. Because it presents in a similar fashion to a metastatic disease, which is more common in the United States, a diagnosis of spinal TB is often delayed, resulting in long-term disability. A high clinical suspicion coupled with appropriate imaging studies helps in prompt diagnosis and the rapid institution of treatment. Anti-TB drugs are effective to treat spinal TB, but surgery is required in refractory disease, abscess formation, vertebral collapse, and/or nerve compression. We present 2 cases of spinal TB: one responded very well to medical treatment; the other required adjunct surgery.
1 February 2021 in Clinical Lymphoma Myeloma and Leukemia
Background: Diabetes mellitus (DM) affects over 30 million Americans with an estimated annual cost of $327 billion in 2017. Patients with diabetes, especially with financial and/or social hardships, pose challenges in achieving target hemoglobin A1c (HbA1c) values. Understanding patient-specific barriers offer opportunities to improve outcomes in patient care. Objective: We aimed to improve a patient’s glycemic control by reducing barriers to care. Furthermore, we evaluated the impact that a resident quality improvement effort had on providing high value diabetic care. Methods: We performed a retrospective cohort study of patients with HbA1c >9.0% in an underserved, resident-run clinic. Patients were surveyed on their knowledge of diabetes and reported obstacles to achieve diabetic control. We then implemented a 12 -month customized, patient-directed, multi-modal, multidisciplinary intervention. Results: Ninety-four patients with HbA1c >9.0% were identified, 65 surveyed, and 51 included in the intervention phase. After the intervention phase, re-evaluation of HbA1c in a paired sample comparison showed that the average HbA1c had decreased by 1.41% (11.28% vs. 9.87%, p < 0.01). Among the patients included in the intervention group, approximately 8% had their HbA1c reduced by ≥50% from their baseline, 23% had their HbA1c reduced by ≥25% from their baseline and 49% had their HbA1c reduced by ≥10% from their baseline. Conclusions: A strategically designed, a patient-centered customized intervention can have a positive impact on a patient’s diabetic control.