Fatty acid binding protein 5 (FABP5), an intracellular lipid binding protein, has been shown to play a role in various cancers, including breast cancer. However, FABP5 and its role in triple negative breast cancer (TNBC) have not been studied. We show FABP5 protein expression correlates with TNBC, high grade tumors, and worse disease-free survival in a tissue microarray containing 423 breast cancer patient samples. High FABP5 expression significantly correlates with epidermal growth factor receptor (EGFR) expression in these samples. Decreased tumor growth and lung metastasis were observed in FABP5−/− mice othotopically injected with murine breast cancer cells. FABP5 loss in TNBC tumor cells inhibited motility and invasion. Mechanistic studies revealed that FABP5 knockdown in TNBC cells results in decreased EGFR expression and FABP5 is important for EGF-induced metastatic signaling. Loss of FABP5 leads to proteasomal targeting of EGFR. Our studies show that FABP5 has a role in both host and tumor cell during breast cancer progression. These findings suggest that FABP5 mediates its enhanced effect on TNBC metastasis, in part, through EGFR, by inhibiting EGFR proteasomal degradation. These studies show, for the first time, a correlation between FABP5 and EGFR in enhancing TNBC metastasis through a novel mechanism.

OBJECTIVEThe importance of maintaining mean arterial pressure (MAP) > 85 mm Hg for patients with acute spinal cord injury (SCI) is well documented, because systemic hypotension greatly increases the risk of secondary SCI. Current literature focuses on the ICU setting; however, there is a paucity of data describing the changes in MAP in the operating room (OR). In the present study, the authors investigated the incidence of intraoperative hypotension for patients with acute traumatic SCI as well as any associated factors that may have impacted these findings.METHODSThis retrospective study was performed at a level 1 trauma center from 2015 to 2016. All patients with American Spinal Injury Association (ASIA) score A–D acute traumatic SCIs from C1 to L1 were identified. Those included underwent spinal instrumentation and/or laminectomy decompression. Associated factors investigated include the following: age, body mass index, trauma mechanism of injury, Injury Severity Score, level of SCI, ASIA score, hospital day of surgery, total OR time, need for laminectomy decompression, use of spinal fixation, surgical positioning, blood loss, use of blood products, length of hospital stay, length of ICU stay, and discharge disposition. Intraoperative minute-by-minute MAP recordings were used to determine time spent in various MAP ranges.RESULTSThirty-two patients underwent a total of 33 operations. Relative to the total OR time, patients spent an average of 51.9% of their cumulative time with an MAP < 85 mm Hg. Furthermore, 100% of the study population recorded at least one MAP measurement < 85 mm Hg. These hypotensive episodes lasted a mean of 103 cumulative minutes per operative case. Analysis of associated factors demonstrated that fall mechanisms of injury led to a statistically significant increase in intraoperative hypotension compared to motor vehicle collisions/motorcycle collisions (p = 0.033). There were no significant differences in MAP recordings when analyzed according to all other associated factors studied.CONCLUSIONSThis is the first study reporting the incidence of intraoperative hypotension for patients with acute traumatic SCIs, and the results demonstrated higher proportions of relative hypotension than previously reported in the ICU setting. Furthermore, the authors identified that every patient experienced at least one MAP below the target value, which was much greater than the initial hypothesis of 50%. Given the findings of this study, adherence to the MAP protocol intraoperatively needs to be improved to minimize the risk of secondary SCI and associated deleterious neurological outcomes.

ObjectiveCortical bone trajectory pedicle screws (CBT) have a different trajectory compared to traditional pedicle screws (PS) and they may confer biomechanical advantages in some patient populations. We hypothesize that the placement of CBT in traumatic thoracolumbar fractures could be an alternative technique to the traditional utilization of PS.MethodsSingle surgeon, retrospective study was performed at a Level 1 Trauma Center from 2013 to 2017. All patients aged between 18 and 90 years with operative AO classification A, B, and C traumatic thoracolumbar fractures were included. Patients with pathological fractures, active spinal infections, or history of vertebral augmentation were excluded. Age, injury severity score (ISS), AO classification, operative time, estimated blood loss (EBL), length of stay (LOS), and presence of proximal junctional kyphosis (PJK) or construct failure were compared between CBT and PS groups. The PS group was further separated into open reduction internal fixation (ORIF) and minimally invasive spine (MIS) groups. All CBT and ORIF cases were completed via open incisions allowing arthrodesis of the involved lamina and facet joints whereas no arthrodesis was completed in the MIS patients. Choice of technique was at the attending surgeon’s discretion.ResultsThe study included 71 patients, out of which 12 received CBT and 59 received PS. Of the 59 PS patients, 39 were ORIF and 20 were MIS. The average operative time was 22.9 minutes less in CBT compared to ORIF (p = 0.24). EBL was 337.50 mL for CBT, 184.33 mL for MIS, and 503.33 mL for ORIF (p = 0.01) demonstrating that MIS technique results in a significantly reduced blood loss. However, EBL was comparable for CBT versus MIS (p > 0.05). ISS was not significantly different between the three groups (p = 0.89). LOS was 4.06 days fewer for CBT patients compared to ORIF patients (p = 0.36). There was one case of construct failure as well as one case of incisional site infection in the PS group, but none were found in the CBT group. Instances of PJK complications were determined by the change in the Cobb angle over time and they were not statistically different between the three groups (p = 0.68).ConclusionsCBT is noninferior to PS in the fixation of unstable adult traumatic thoracolumbar fractures. With the exception of EBL, CBT was not statistically different compared to MIS and ORIF. This study establishes a precedent to expand the application of this new technique and investigate with larger sample sizes.

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has a poor prognosis for patients, not only due to its aggressive nature, but also due to the lack of effective therapeutic strategies. High mortality is associated with metastasis of the primary TNBC. We analyzed the role of fatty acid binding protein 5 (FABP5), an intracellular fatty acid transport protein, in aggressive breast cancers, especially TNBC. FABP5 expression was analyzed in a tumor microarray (TMA) containing 423 breast cancer patient samples and found that FABP5 expression is associated with tumor grade, triple negative status, and disease-free survival. Next, a mechanistic approach was taken and found that FABP5 knockdown TNBC cell lines express lesser EGFR protein compared to control, and upon EGFR activation express less phospho-FAK and phospho-Pyk2. We found that EGFR was not down regulated at the transcriptional level in FABP5 knockout cells. Further analysis indicated the role for Cbl, an E3 ubiquitin-protein ligase, as a potential mechanistic target for the down-regulation of EGFR protein in FABP5 knockdown cell lines. EGFR is over-expressed in aggressive breast cancers, especially TNBC. Though EGFR is highly expressed in aggressive subtypes of breast cancer, targeted therapeutic strategies have not been successful in clinic. EGFR has been shown to be involved in distant metastasis in aggressive breast cancers. We found a correlation between FABP5 and EGFR expression and metastasis-free survival using publically available datasets from The Cancer Genome Atlas. We next studied the functional consequence of FABP5 knockdown in TNBC cell lines. We showed that EGF-induced FABP5 knockdown cells migrated less compared to control. Additionally, FABP5 knockdown cells were significantly less able to migrate into a wound in response to EGF stimulation. EGF-induced cell attachment of FABP5 knockdown cells is significantly decreased compared to control. Our findings suggest FABP5 modulates metastatic potential of TNBC through alterations in EGFR expression and downstream migratory signaling molecules. Citation Format: Catherine A Powell, Mohd W Nasser, Jacob C Wochna, Konstantin Shilo, Xiaoli Zhang, Ramesh K Ganju. Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-35.