NGFI-A Binding Protein 2 Promotes EGF-Dependent HNSCC Cell Invasion.

NGFI-A binding protein 2 (NAB2) represses the transcriptional activation of early growth response protein-1 (EGR1), a tumor-suppressor. However, Epidermal Growth Factor (EGF) promotes tumor progression even with significant EGR1 upregulation. The molecular mechanism through which NAB2 is involved in cancer is largely unknown. Therefore, we evaluated how the NAB2-mediated suppression of EGR1 facilitates head and neck squamous cell carcinoma (HNSCC) cancer progression, in association with Sp1, which competes with EGR1 as a transcriptional regulator. The effect of NAB2 on EGR1/SP1 binding to the consensus promoter sequences of MMP2 and MMP9 was evaluated by chromatin immunoprecipitation (ChIP) and promoter luciferase assay. The correlation between EGR1-NAB2 expression and metastatic status was investigated using The Cancer Genome Atlas (TCGA) for HNSCC patients. Our data showed that NAB2 knockdown in FaDu and YD-10B HNSCC cells alleviated EGF-dependent increase of Matrigel invasion. In addition, NAB2 upregulation in EGF-treated FaDu cell diminishes EGR1 transcriptional activity, resulting in the upregulation of Sp1-dependent tumor-promoting genes. TCGA data analysis of 483 HNSCC tumors showed that higher levels of both EGR1 and NAB2 mRNA were significantly associated with metastasis, corresponding to in vitro results. Our data suggest that NAB2 upregulation facilitates EGF-mediated cancer cell invasion through the transactivation of Sp1-dependent tumor-promoting genes. These results provide insight into the paradoxical roles of EGF-EGR1 in cancer progression.

Early Growth Response 1-Dependent Downregulation of Matrix Metalloproteinase 9 and Mouse Double Minute 2 Attenuates Head and Neck Squamous Cell Carcinoma Metastasis.

BACKGROUND/AIMS: The functional relevance of early growth response-1 (EGR1) on cancer invasion remains controversial. The effect of EGR1 on the expression of MMP9, which is important for HNSCC invasion, is still disputed. There is no previous data showing the effect of EGR1 on mouse double minute 2 (MDM2), an enhancer of matrix metalloproteinase 9 (MMP9) expression. Our aim is to clarify the negative correlation between EGR1 expression and head and neck squamous cell carcinoma (HNSCC) metastasis. METHODS: EGR1 mRNA and protein expressions were compared in normal and HNSCC tissues using The Cancer Genome Atlas (TCGA) dataset analysis or immunohistochemistry (IHC), respectively. In vitro cell invasion was evaluated Matrigel invasion assay. EGR1-dependent inhibition of MDM2 transcription was assessed by promoter-luciferase assay and chromatin immunoprecipitation (ChIP). RESULTS: TCGA data showed that EGR1 mRNA levels are significantly higher in normal oral tissues as compared with HNSCC tumor tissues (adjusted P = 1.64x10-16). In addition, nonmetastatic HNSCC tissues showed significantly higher EGR1 mRNA levels as compared with metastatic tissues (adjusted P = 0.023). IHC analysis showed that primary tumor tissues expressed significantly higher levels of nuclear EGR1 compared with paired metastatic lymph node tissues (P < 0.05). EGR1 overexpression downregulated MMP9 and MDM2 protein expression. Consistent with these observations, TCGA data analysis found significantly fewer metastatic patients among a subgroup of population presenting higher EGR1 expressions with lower MMP9 and/or MDM2. CONCLUSION: Our data suggests that EGR1 prevents HNSCC metastasis through downregulation of MMP9 and MDM2. EGR1 might be a potential candidate to attenuate HNSCC metastasis.

Morphometric Study of the Lumbar Posterior Longitudinal Ligament.

OBJECTIVE: Morphometric data for the lumbar posterior longitudinal ligament (PLL) was investigated to identify whether there is a difference in the morphometry of the PLL of the lumbar spine at each level with respect to the pattern of intervertebral disc displacement. METHODS: In 14 formalin-fixed adult cadavers (12 males and 2 females), from L1 to L5, the authors measured the width and height of the PLL and compared them with other landmarks such as the disc and the pedicle. RESULTS: Horizontally, at the upper margin of the disc, the central portion of the superficial PLL covered 17.8-36.9% of the disc width and the fan-like portion of the PLL covered 63.9-76.7% of the disc width. At the level of the median portion of the disc, the PLL covered 69.1-74.5% of the disc width. Vertically, at the level of the medial margin of the pedicle, the fan-like portion of the PLL covered 23.5-29.9% of the disc height. In general, a significant difference in length was not found in the right-left and male-female comparisons. CONCLUSION: This study presents the morphometric data on the pattern of intervertebral disc displacement and helps to improve the knowledge of the surgical anatomy of the lumbar PLL.

Geographic Analysis of Neurosurgery Workforce in Korea.

OBJECTIVE: In respect of the health and safety of the public, universal access to health care is an issue of the greatest importance. The geographic distribution of doctors is one of the important factors contributing to access to health care. The aim of this study is to assess the imbalances in the geographic distribution of neurosurgeons across Korea. METHODS: Population data was obtained from the National Statistical Office. We classified geographic groups into 7 metropolitan cities, 78 non-metropolitan cities, and 77 rural areas. The number of doctors and neurosurgeons per 100000 populations in each county unit was calculated using the total number of doctors and neurosurgeons at the country level from 2009 to 2015. The density levels of neurosurgeon and doctor were calculated and depicted in maps. RESULTS: Between 2009 and 2015, the number of neurosurgeons increased from 2002 to 2557, and the ratio of neurosurgeons per 100000 populations increased from 4.02 to 4.96. The number of neurosurgeons per 100000 populations was highest in metropolitan cities and lowest in rural areas from 2009 to 2015. A comparison of the geographic distribution of neurosurgeons in 2009 and 2015 showed an increase in the regional gap. The neurosurgeon density was affected by country unit characteristics (p=0.000). CONCLUSION: Distribution of neurosurgeons throughout Korea is uneven. Neurosurgeons are being increasingly concentrated in a limited number of metropolitan cities. This phenomenon will need to be accounted when planning for a supply of neurosurgeons, allocation of resources and manpower, and the provision of regional neurosurgical services.

A Morphometric Study of the Obturator Nerve around the Obturator Foramen.

OBJECTIVE: Obturator neuropathy is a rare condition. Many neurosurgeons are unfamiliar with the obturator nerve anatomy. The purpose of this study was to define obturator nerve landmarks around the obturator foramen. METHODS: Fourteen cadavers were studied bilaterally to measure the distances from the nerve root to relevant anatomical landmarks near the obturator nerve, including the anterior superior iliac spine (ASIS), the pubic tubercle, the inguinal ligament, the femoral artery, and the adductor longus. RESULTS: The obturator nerve exits the obturator foramen and travels infero-medially between the adductors longus and brevis. The median distances from the obturator nerve exit zone (ONEZ) to the ASIS and pubic tubercle were 114 mm and 30 mm, respectively. The median horizontal and vertical distances between the pubic tubercle and the ONEZ were 17 mm and 27 mm, respectively. The shortest median distance from the ONEZ to the inguinal ligament was 19 mm. The median inguinal ligament lengths from the ASIS and the median pubic tubercle to the shortest point were 103 mm and 24 mm, respectively. The median obturator nerve lengths between the ONEZ and the adductor longus and femoral artery were 41 mm and 28 mm, respectively. CONCLUSION: The obturator nerve exits the foramen 17 mm and 27 mm on the horizontal and sagittal planes, respectively, from the pubic tubercle below the pectineus muscle. The shallowest area is approximately one-fifth medially from the inguinal ligament. This study will help improve the accuracy of obturator nerve surgeries to better establish therapeutic plans and decrease complications.

Morphometric study of the nerve roots around the lateral mass for posterior foraminotomy.

OBJECTIVE: Morphometric data on dorsal cervical anatomy were examined in an effort to protect the nerve root near the lateral mass during posterior foraminotomy. METHODS: Using 25 adult formalin-fixed cadaveric cervical spines, measurements were taken at the lateral mass from C3 to C7 via a total laminectomy and a medial one-half facetectomy. The morphometric relationship between the nerve roots and structures of the lateral mass was investigated. Results from both genders were compared. RESULTS: Following the total laminectomy, from C3 to C7, the mean of the vertical distance from the medial point of the facet (MPF) of the lateral mass to the axilla of the root origin was 3.2-4.7 mm. The whole length of the exposed root had a mean of 4.2-5.8 mm. Following a medial one-half facetectomy, from C3 to C7, the mean of the vertical distance to the axilla of the root origin was 2.1-3.4 mm, based on the MPF. Mean vertical distances from the MPF to the medial point of the root that crossed the inferior margin of the intervertebral disc were 1.2-2.7 mm. The mean distance of the exposed root was 8.2-9.0 mm, and the mean angle between the dura and the nerve root was significantly different between males and females, at 53.4-68.4 degrees . CONCLUSION: These data will aid in reducing root injuries during posterior cervical foraminotomy.

Sudden migration of a thalamic hemorrhage into the ventricles.

Spontaneous intracerebral hemorrhage (ICH) is a common condition that often leads to death or disability. Accurate prediction of the outcome and decisions regarding the treatment of ICH patients are important issues. We report a case of thalamic hemorrhage with an intraventricular hemorrhage that was suddenly migrated into the third and fourth ventricles in its entirety 8 hours after symptom onset. To our knowledge, this case is the first report of spontaneous migration of thalamic ICH into ventricles, and we suggest a possible mechanism for this case with a brief review of the literature.