Supplementary Figure 2 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer

Supplementary Methods and Figures 1-2 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer

Supplementary Figure 1 from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer

Lyon et al. recently examined survival outcomes among patients with metastatic renal cell carcinoma (mRCC) treated with or without complete surgical metastasectomy (SM) during an era when targeted therapy and checkpoint inhibitors were available (1).

Study Design. Quantitative analysis of endogenous messenger ribonucleic acid ( mRNA) expression of anabolic cytokines in the anulus fibrosus and nucleus pulposus tissue from the intervertebral discs of young and old rabbits was performed.Objectives. To measure the expression of anabolic cytokines bone morphogenetic protein-2 (BMP-2), BMP-7, transforming growth factor-beta (TGF-beta), and insulin-like growth factor-I (IGF-I) in the anulus fibrosus and nucleus pulposus tissue from young and old rabbits to determine if there are differences with age.Summary of Background Data. Disc degeneration increases with age and is associated with compromised disc chondrocytic function. Molecules such as BMP-2, BMP-7, TGF-beta, and IGF-I are known to up-regulate disc cell synthesis of key chondrocytic matrix molecules in vitro, and have been proposed as therapeutic agents to prevent disc degeneration. Previous studies have shown that exogenous anabolic cytokines can up-regulate disc-cell function both in vitro and in vivo, however, the endogenous expression of anabolic cytokines in the disc is still unknown.Methods. New Zealand white rabbits aged 3 years (old) and 6 months (young) were used. Quantitative realtime polymerase chain reaction was performed to measure the mRNA levels of BMP-2, BMP-7, TGF-beta 1, and IGF-I from anulus fibrosus and nucleus pulposus tissue from young and old rabbits. The discs form the young rabbits represent nondegenerated discs, and the discs from the old rabbits represent discs at the onset of degeneration.Results. In the nucleus pulposus, the mRNA levels, given as a ratio of old to young, were 3.6 for BMP-2 (P = 0.004), 61 for BMP-7 ( P = 0.02), 4.0 for TGF-beta 1 ( P = 0.3), and 0.6 for IGF-I (P = 0.2). In the anulus fibrosus, the mRNA levels, given as a ratio of old to young, were 1.6 for BMP-2 ( P = 0.07), 4.6 for BMP-7 ( P = 0.004), 2.9 for TGF-beta 1 (P = 0.01), and 2.0 for IGF-1 (P = 0.1). Conclusion. The disc tissue from the old rabbits as compared to the young rabbits showed, in general, significantly higher mRNA levels of endogenous BMP- 2, BMP- 7, and TGF-beta in both the anulus fibrosus and nucleus pulposus. The similar patterns of up-regulation in gene expression with age shown by these 3 anabolic cytokines suggest a common pathway in terms of regulation and transcription in the early stage of disc degeneration. The knowledge of the age-related pattern in endogenous gene expression of these anabolic cytokines could provide important information for clinical interventional therapy.

BACKGROUND CONTEXT: The cellular and molecular basis of age related disc degeneration is poorly understood. One possibility is that cells from older individuals may have a decreased synthetic capacity for key molecules such as sulfated-glycosaminoglycans (sGAG), aggrecan (a key proteoglycan), and collagen II (a key disc collagen). In experiment (1), we determined whether there is a difference in the synthetic metabolism of matrix components between disc cells from young and old rabbits. Then in experiment (2) we tested whether cells from older animals could upregulate their synthetic function in respond to stimulation by LMP-1 overexpression, in hopes of developing a method of compensating for any decrease in synthetic capacity of cells from older animals.

Background: The hypothesis that injecting bone cement adjacent to one or both endplates would bring about degeneration in the intervening disc was tested. nucleus and the annulus and clear histologic changes in some of the discs.Methods: In 11 dogs, bone cement was injected just below the superior endplates of L1, L2, and L3 to block the nutritional supply through these endplates to the three intervertebral discs T13-L1, L1-L2, and L2-L3. In one other dog, both the superior and the inferior endplates of the same discs (T13-L1, L1-L2, and L2-L3) were blocked with bone cement. All 12 dogs were euthanized between 31 and 70 weeks after the Surgery. The three experimental discs (T13-L1, L1-L2,and L2-L3) and two control discs (T12-T13 and L4-L5) were excised and assessed using enzyme-linked immunosorbent assay (ELISA) and histology.Results: Radiographs of the lumbar spine at the time of death did not show any signs of disc bulging, disc space narrowing, or peripheral osteophyte formation in any of the 12 dogs. The experimental discs as well as the control discs appeared normal in every dog. After the discs were bisected, they were carefully inspected for any visible signs of degeneration. The experimental discs showed no clear signs of disc degeneration and were not distinguishable from the control discs on a gross level. The numerical results from the ELISA showed that in the experimental discs as opposed to the control discs, there were significant increases in proteoglycan content in both the nucleus (P = 0.033) and annulus (P = 0.01) and clear histologic changes in some of the discs.Conclusion: The results show that injecting bone cement adjacent to one or both endplates for up to 70 weeks does not produce degeneration in any visible form in the intervening disc. There were no disc bulging, no apparent annular fissures, and no disc spacing narrowing. There were, however, increases in protoglycan content in both the nucleus and the annulus and clear histologic changes in some of the discs.

Study Design. A case of idiopathic focal vertebral body osteonecrosis without vertebral collapse is reported. Objectives. To report a rare case of focal vertebral osteonecrosis and to clarify the features of imaging studies. Summary of Background Data There are no previous reports describing focal vertebral body necrosis without collapse in the literature. Methods. A case report and literature review are presented. Results. Imaging studies demonstrated: 1) sclerotic change on computed tomography scan; 2) low intensity on T1, high intensity on T2 with clear margin, and no gadolinium enhancement on magnetic resonance imaging; and 3) no uptake on bone scan. Histologic examination revealed empty lacunas, fatty necrosis with vacuolar degeneration, and cell debris compatible with bone marrow necrosis. Conclusion. Vertebral body osteonecrosis must be considered a possible diagnosis of patients presenting with low intensity on T1, high intensity on T2 with clear margin, and no gadolinium enhancement on magnetic resonance imaging.

Study Design. A chondroblastoma of the posterior component of the seventh cervical vertebra with tetraparesis was reported. Imaging studies showed an expansile destructive lesion with mineralization. Objectives. To emphasize the occurrence of tetraparesis caused by chondroblastoma in the cervical spine. Summary of Background Data. Chondroblastoma is a rare benign neoplasm of the bone. Only eight cases of chondroblastoma occurring in the vertebra are reported in the literature, including five in the cervical vertebrae. However, there was no reported case of tetraparesis in the literature. Methods. A 19-year-old man had a tetraparesis caused by chondroblastoma of the posterior component of the seventh cervical vertebra, which invaded the vertebral body with an extraosseous involvement. Imaging studies showed an expansile destructive lesion with mineralization. Curettage of the lesion was performed from both anterior and posterior approaches. The defect of the vertebral body was reconstructed by autologous iliac bone graft with posterior fusion using the Luque instrumentation system. Results. Histologically, the tumor cells were forming cartilage with round or oval nuclei, which often were indented or had a longitudinal groove. There was no sign of local recurrence, and the neurologic deficit had fully recovered 2 years and 3 months after surgery. Conclusions. Chondroblastoma should be included in the differential diagnosis of lytic expansile destructive lesion of the spine, although there is an extraosseous involvement. Prompt adequate surgery should be performed as soon as possible after establishment of the correct histologic diagnosis to restore the neurologic deficit.

STUDY DESIGN:A matched cohort clinical and radiographic retrospective analysis of laminoplasty and laminectomy with fusion for the treatment of multilevel cervical myelopathy.OBJECTIVES:To compare the clinical and radiographic outcomes of two procedures increasingly used to treat multilevel cervical myelopathy.SUMMARY OF BACKGROUND DATA:Traditional methods of treating multilevel cervical myelopathy (laminectomy and corpectomy) are reported to have a notable frequency of complications. Laminoplasty and laminectomy with fusion have been advocated as superior procedures. A comparative study of these two techniques has not been reported.METHODS:Medical records of all patients treated for multilevel cervical myelopathy with either laminoplasty or laminectomy with fusion between 1994 and 1999 at our institution were reviewed. Thirteen patients that underwent laminectomy with fusion were matched with 13 patients that underwent laminoplasty. All patients and radiographs were independently evaluated at latest follow-up by a single physician.RESULTS:Cohorts were well matched based on patient age, duration of symptoms, and severity of myelopathy (Nurick grade) before surgery. Mean independent follow-up was similar (25.5 and 26.2 months). Both objective improvement in patient function (Nurick score) and the number of patients reporting subjective improvement in strength, dexterity, sensation, pain, and gait tended to be greater in the laminoplasty cohort. Whereas no complications occurred in the laminoplasty cohort, there were 14 complications in 9 patients that underwent laminectomy with fusion patients. Complications included progression of myelopathy, nonunion, instrumentation failure, development of a significant kyphotic alignment, persistent bone graft harvest site pain, subjacent degeneration requiring reoperation, and deep infection.CONCLUSIONS:The marked difference in complications and functional improvement between these matched cohorts suggests that laminoplasty may be preferable to laminectomy with fusion as a posterior procedure for multilevel cervical myelopathy.