Hormonally regulated survival factors can have an important role in breast cancer. Here we elucidate G1P3, a survival protein induced by interferons (IFNs), as a target of estrogen signaling and a contributor to poor outcomes in estrogen receptor-positive (ER þ ) breast cancer. Compared with normal breast tissue, G1P3 was upregulated in the malignant epithelium (50 Â higher) and was induced by estrogen ex vivo. In accord with its overexpression in early stages of breast cancer (hyperplasia and ductal carcinoma in situ), in morphogenesis assays G1P3 enhanced the survival of MCF10A acinar luminal cells causing hyperplasia by suppressing detachmentinduced loss of mitochondrial potential and apoptosis (anoikis). In cells undergoing anoikis, G1P3 attenuated the induction of Bim protein, a proapoptotic member of the Bcl-2 family and reversed the downmodulation of Bcl-2 protein. Downregulation of G1P3 induced spontaneous apoptosis in BT-549 breast cancer cells and significantly reduced the growth of ER þ breast cancer cell MCF7 (Pp0.01), further suggesting its prosurvival activity. In agreement with its induction by estrogen, G1P3 antagonized tamoxifen, an inhibitor of ER in MCF7 cells. More importantly, elevated expression of G1P3 was significantly associated with decreased relapsefree and overall survival in ER þ breast cancer patients (Pp0.01). Our studies suggest that elevated expression of G1P3 may perturb canonical tumor-suppressing activity of IFNs partly by affecting the balance of pro-and antiapoptotic members of Bcl-2 family proteins, leading to breast cancer development and resistance to therapies.
Background: Trigger finger is characterized by the inability to smoothly flex and extend the digit. Corticosteroids are an accepted non-surgical treatment option and can be delivered via two techniques. While the palmar approach is more commonly used, some have suggested that the mid-axial approach may be less painful for patients and yield higher intrasheath injection rates. The purpose of this study is to compare the accuracy of the palmar and midaxial approaches for delivery of corticosteroids into the flexor tendon sheath using radio-opaque dye in a cadaver model. Methods: A total of 50 injections were performed, 25 via midaxial technique and 25 via palmar technique. A one inch, 25-gauge needle was used to inject 1 mL of Isovue contrast dye into the flexor tendon sheath under live fluoroscopy. The fluoroscopic images were examined after injection to determine intrasheath versus extrasheath delivery of the dye, with visualization of contrast filling the sheath defining a successful injection. Results: The midaxial approach had a success rate of 52% compared to the conventional palmar approach success rate of 36%, p = 0.5. The ring finger is the most common location of trigger finger and the rates of success were equal between groups for this digit (80%). Conclusions: Based on our findings, there is no statistical difference in the accuracy of intrasheath injection between the midaxial technique and palmar technique. The midaxial technique can be considered as an alternative to the palmar technique for trigger finger injection.
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