Citations

Abstract Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240–9. ©2011 AACR.

Abstract BACKGROUND: Ventral decompression with posterior stabilization is the preferred treatment for symptomatic irreducible basilar invagination. Endoscopic image-guided transcervical odontoidectomy (ETO) may allow for decompression with limited morbidity. OBJECTIVE: To describe the perioperative outcomes of patients undergoing anterior decompression of basilar invagination with the use of ETO. METHODS: Fifteen patients who had a follow-up of at least 16 months were retrospectively reviewed. Intraoperatively, the vertebral body of C2 was removed and the odontoid was resected in a “top-down” manner using endoscopic visualization and frameless stereotactic navigation. Posterior instrumented stabilization was subsequently performed. RESULTS: The average (± standard deviation) age of the patients was 42.6 ± 24.5 (range, 11–72) years. Postoperative complications occurred in 6 patients, including a urinary tract infection (n = 2), upper airway swelling (n = 2), dysphagia (n = 2), gastrostomy tube placement (n = 1), and an asymptomatic pseudomeningocele (n = 1). No patients required a tracheostomy, had bacterial meningitis, or developed a venous thromboembolic event; only 1 patient was intubated for more than 48 hours postoperatively. With a mean follow-up of 41.9 ± 14.4 (range, 16–59) months, myelopathy improved in all patients and no patient experienced late neurological deterioration. The mean modified Japanese Orthopedic Association (JOA) score increased from 11.2 ± 4.2 to 15.9 ± 1.4 (P = .002). Patients with a diagnosis other than rheumatoid arthritis or who had a higher preoperative JOA score had a significantly better postoperative neurological recovery (P = .005). CONCLUSION: ETO may be a valid treatment for patients with symptomatic irreducible basilar invagination that avoids some of the morbidity of transoral surgery and leads to long-term improvement in myelopathy.

Abstract Recent advances in understanding the epidemiology, genetics, diagnosis, clinical presentations, skeletal involvement, and therapeutic approaches to hypoparathyroidism led to the First International Workshop on Hypoparathyroidism that was held in 2009. At this conference, a group of experts convened to discuss these issues with a view towards a future research agenda for this disease. This review, which focuses primarily on hypoparathyroidism in the adult, provides a comprehensive summary of the latest information on this disease. © 2011 American Society for Bone and Mineral Research

With improved treatments and increasingly life expectancy, the burden of metastatic disease in the spine is expected to rise. The role of conventional surgery for spinal metastases is well established but often involves procedures of large magnitude. We describe minimally invasive techniques for spinal stabilization and decompression in patients with symptomatic metastatic disease of the spine.

Abstract Dendritic cells (DCs) are professional APCs that reside in peripheral tissues and survey the body for pathogens. Upon activation by inflammatory signals, DCs undergo a maturation process and migrate to lymphoid organs, where they present pathogen-derived Ags to T cells. DC migration depends on tight regulation of the actin cytoskeleton to permit rapid adaptation to environmental cues. We investigated the role of hematopoietic lineage cell-specific protein 1 (HS1), the hematopoietic homolog of cortactin, in regulating the actin cytoskeleton of murine DCs. HS1 localized to lamellipodial protrusions and podosomes, actin-rich structures associated with adhesion and migration. DCs from HS1−/− mice showed aberrant lamellipodial dynamics. Moreover, although these cells formed recognizable podosomes, their podosome arrays were loosely packed and improperly localized within the cell. HS1 interacts with Wiskott–Aldrich syndrome protein (WASp), another key actin-regulatory protein, through mutual binding to WASp-interacting protein. Comparative analysis of DCs deficient for HS1, WASp or both proteins revealed unique roles for these proteins in regulating podosomes with WASp being essential for podosome formation and with HS1 ensuring efficient array organization. WASp recruitment to podosome cores was independent of HS1, whereas HS1 recruitment required Src homology 3 domain-dependent interactions with the WASp/WASp-interacting protein heterodimer. In migration assays, the phenotypes of HS1- and WASp-deficient DCs were related, but distinct. WASp−/y DCs migrating in a chemokine gradient showed a large decrease in velocity and diminished directional persistence. In contrast, HS1−/− DCs migrated faster than wild-type cells, but directional persistence was significantly reduced. These studies show that HS1 functions in concert with WASp to fine-tune DC cytoarchitecture and direct cell migration.

Abstract After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and “in situ” lesions, disorders with limited capacity for clinical progression, lesions without current International Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency-associated lymphoproliferative disorders. WHO subtypes are defined in hierarchical groupings, with newly defined groups for small B-cell lymphomas with plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We suggest approaches for applying the hierarchical classification in various epidemiologic settings, including strategies for dealing with multiple coexisting lymphoma subtypes in one patient, and cases with incomplete pathologic information. The pathology materials useful for state-of-the-art epidemiology studies are also discussed. We encourage epidemiologists to adopt the updated InterLymph hierarchical classification, which incorporates the most recent WHO entities while demonstrating their relationship to older classifications.

Abstract The microanatomic distribution of several noncollagenous proteins (NCPs) in bone matrix was examined by immunohistochemical analysis of glycol-methyl methacrylate-embedded normal adult human bone biopsies. Osteopontin and bone sialoprotein stained throughout the lamellae of both trabecular and cortical bone. Cement lines (cortical and trabecular) and the mineralized matrix immediately adjacent to each Haversian canal were intensely stained. Osteocalcin was detected in cement lines; however, lamellar staining varied depending on the location within the individual unit of bone. In cortical bone, the inner concentric lamellae of osteons were often unstained but the outer lamellae were heavily stained for osteocalcin. Osteonectin was not detected in cement lines and in most specimens revealed a pattern similar to that of osteocalcin with respect to the absence of immunostaining within the inner concentric lamellae. Decorin was prominent in the perilacunar matrix, the canaliculi of osteocytes, and the matrix immediately adjacent to quiescent Haversian canals. Biglycan appeared evenly distributed throughout cortical and trabecular bone matrix. These results suggest that the incorporation of NCPs into matrix may vary depending on the stage of formation of individual bone units. The specific distribution and spatial relationship of these NCPs may be related to the function of each protein during bone resorption and formation. The distinct patterns of NCP localization in bone support the hypothesis that in addition to their structural and mineral-inducing properties, these proteins may influence the events associated with bone remodeling, such as recruitment, attachment, differentiation, and activity of bone cells.

Intracranial aneurysms in the pediatric population are relatively rare entities. Immunocompromised patients (often from HIV/AIDS or pharmacological immunosuppression) represent a significant fraction of children with cerebral aneurysms. One proposed mechanism of aneurysm formation in these patients is from direct infection of the affected arteries. In this study, the authors report on a case of a 14-year-old girl with common variable immunodeficiency with T-cell dysfunction and a CSF polymerase chain reaction test positive for varicella-zoster virus who underwent evaluation for carotid and basilar artery fusiform aneurysms.