Elevated expression of cholesterol transporter LRP-1 is crucially implicated in the pathobiology of glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain tumor with a grave prognosis. The present study evaluated the expression of Cholesterol transporter [importer -Lipoprotein Receptor-related Protein-1 (LRP-1) and exporter -ATP-binding cassette transporters-1 (ABCA-1)] in GBM and their implications in tumor-biology, clinical outcome and therapeutic potentials. The mRNA and protein expression was assessed by qRT-PCR and immunohistochemistry, respectively, in 85 GBMs. For comparison, 25 lower-grade astrocytomas (IDH-mutant, grade-2/3) [LGA] 16 cases of high-grade astrocytomas (IDH-mutant, grade-4) [HGA] were also evaluated. In-vitro analysis was performed on U87MG and LN229 glioma cell line. The expression of LRP-1 (mRNA and protein) was significantly higher in GBM than LGA, HGA and normal brain (NB) [p-values 0.007, 0.003 and <0.001 for mRNA; 0.024, <0.001 and <0.001 for immunohistochemistry]. Majority of the GBMs (82.4%) showed strong immunoreactivity for LRP-1, and all tumor cases were positive while the normal brain was negative. LRP-1 immunoreactivity positively correlated with the MIB-1 labeling index (p-value-0.013). LRP-1 knockdown in-vitro was associated with decreased cell survival, proliferation, migration, invasion, and increased apoptosis. Similar effect was also demonstrated by Receptor Associated Protein (RAP), a LRP-1 inhibitory drug. The silencing of LRP-1 was also associated with decreased cholesterol level. The ABCA-1 expression was higher in GBM than LGA and NB (p-value 0.011 and <0.001), however there was no significant association with other parameters. LRP-1 showed a positive correlation with ABCA-1 and associated with decreased expression with LRP-1 knock-down in-vitro. The expression of LRP-1 and ABCA-1 didn't correlate with overall survival in GBMs. Hence, LRP-1 is crucial for the tumor cells' survival and aggressive biological behavior which is maintain through the regulation of high intracellular cholesterol import. Its expression is significantly higher in GBMs and also implicated in the regulation of ABCA-1 expression. Considering its immune-positivity only in the neoplastic cell and strong positivity in GBM it may be a useful adjunct to the diagnosis. For the first time, the present study emphasized its role as a potential therapeutic target in the form of RAP which is presently being used in other neurological diseases under clinical trials.

Recurrent Metastatic Choriocarcinoma Responsive to Etoposide and Cisplatin with Etoposide, Methotrexate, and Dactinomycin: A Case Report.

Choriocarcinoma is a malignant trophoblastic tumour usually of placental origin. It is characterized by early metastasis to the brain and lungs. With early detection, it has a better prognosis with treatment. We report a case of 18 years female at 26 weeks of gestation in her third pregnancy who had a history of treatment for metastatic gestational trophoblastic neoplasm with chemotherapy and radiotherapy two years back. Therefore, she was managed as a case of recurrent choriocarcinoma with brain metastasis with chemotherapy (etoposide and cisplatin with etoposide, methotrexate, and dactinomycin) and was responsive. Her symptoms resolved and ß-human chorionic gonadotropin dropped to normal value (<2.39 mIU/ml) which has shown that timely diagnosis and management can be vital for the successful treatment of brain metastasis. Keywords: chemotherapy; choriocarcinoma; metastasis; recurrence.

Contiguous-Level Unilateral Cervical Spine Facet Dislocation-A Report of a Less Discussed Subtype.

Unilateral facet dislocation of subaxial cervical spine trauma is characterized by dislocation of inferior facet of superior vertebra over the superior facet of inferior vertebra. The injury is due to high-velocity trauma and associated with instability of spinal column. Such unilateral facet dislocations occurring at multiple adjacent levels for some reason are not reported or studied frequently. We have reported two cases of multiple-level dislocation of unilateral facets managed in our hospital with a review of available literature. The injury occurs as one side of the motion segment translates and rotates around an intact facet on the contralateral side. The major mechanism of injury is distractive flexion injury with axial rotation component. The injury is associated with instability secondary to loss of the discoligamentous complex. In cases with multiple-level dislocations of unilateral cervical facets, there are multiple mechanisms associated with significant neurological injury and most of them succumb at the site of injury. Only three other cases are available in English language literature. The neurological outcome is invariably poor. Multiple-level facet dislocations of subaxial cervical spine are reported sparsely in literature. We suspect that due to high-velocity nature of these injuries, most of them succumb soon after injury and not often reported. This article reports two cases of contiguous-level unilateral facet dislocation of subaxial cervical spine with associated injuries and the outcomes with review of literature.

Takayasu's Arteritis with Subcutaneous Nodules in a 4-year -old Child: A Case Report.

A 4-year-old girl who presented with pain in the abdomen, subcutaneous nodule, fever and was later diagnosed with Takayasu arteritis . Oral corticosteroid and methotrexate were started. Childhood TA should be kept in differential diagnosis when presented with subcutaneous nodules and increased acute phase reactants.

Evaluation of outcome of corrective ulnar osteotomy with bone grafting and annular ligament reconstruction in neglected monteggia fracture dislocation in children.

INTRODUCTION: Neglected Monteggia fracture dislocation in the paediatric age group constitutes significant disability in respect to pain, stiffness, deformity, neurological compromise and restriction of activities of daily living. MATERIALS AND METHODS: A longitudinal prospective study was done on 21 children with old Monteggia fracture-dislocation which included 18 cases of Bado type I and 3 cases of Bado type III at the department of orthopaedics, IPGME&R,SSKM hospital, Kolkata, India between 2007 and 2012. All were treated by modified Hirayama corrective osteotomy of ulna with wedge bone grafting along with restoration of its length and reconstruction of annular ligament using Bell Tawse method and fixation of radial head with transcapitellar Kirschner wire. Average follow up period was 5.5 years. RESULTS AND ANALYSIS: Results were evaluated on the basis of 100 point Mayo Elbow Performance Index, radiology and questionnaire. The mean postoperative increase in Mayo Elbow Performance Index score was 30 with average increase in the range of movement by 30o. In three cases, there was subluxation of radial head and in addition one had transient palsy of posterior interosseous nerve. Three cases showed distortion of the radial head which were insignificant functionally. Results of improvement in mean MEPI were analysed by chi-square test and was significant at 0 .01 level of significance. CONCLUSION: Study showed good results with modified Hirayama osteotomy with annular ligament reconstruction using Bell Tawse procedure which is a more biological option for restoration of elbow biomechanics.