ABSTRACT
A 25-year-old man presented to the Emergency department in a rural South African hospital after a left, submental neck stab with a knife. Examination was deemed unremarkable, and the patient was discharged, but re-attended 2 days later complaining of a painful, swollen neck. Further examination identified Horner's syndrome, and further investigation revealed that the blade of the knife had remained in the patient's neck. This was successfully removed in theatre. This case illustrates the importance of careful history, examination and diagnostic imaging in the management of penetrating neck injuries. Horner's syndrome can be easily missed in a busy Emergency department and may indicate life-threatening pathology in the context of neck trauma. The difficulties in assessing and managing this type of injury are discussed.
Subject(s)
Foreign Bodies/surgery , Horner Syndrome/etiology , Neck Injuries/complications , Wounds, Penetrating/complications , Adult , Foreign Bodies/diagnostic imaging , Horner Syndrome/diagnosis , Humans , Male , Neck Injuries/diagnostic imaging , Radiography , Treatment Outcome , Wounds, Penetrating/diagnostic imagingABSTRACT
BACKGROUND: C35 is a 12 kDa membrane-anchored protein endogenously over-expressed in many invasive breast cancers. C35 (C17orf37) is located on the HER2 amplicon, between HER2 and GRB7. The function of over-expressed C35 in invasive breast cancer is unknown. METHODS: Tissue microarrays containing 122 primary human breast cancer specimens were used to examine the association of C35 with HER2 expression. Cell lines over-expressing C35 were generated and tested for evidence of cell transformation in vitro. RESULTS: In primary breast cancers high levels of C35 mRNA expression were associated with HER2 gene amplification. High levels of C35 protein expression were associated with hallmarks of transformation, such as, colony growth in soft agar, invasion into collagen matrix and formation of large acinar structures in three-dimensional (3D) cell cultures. The transformed phenotype was also associated with characteristics of epithelial to mesenchymal transition, such as adoption of spindle cell morphology and down-regulation of epithelial markers, such as E-cadherin and keratin-8. Furthermore, C35-induced transformation in 3D cell cultures was dependent on Syk kinase, a downstream mediator of signalling from the immunoreceptor tyrosine-based activation motif, which is present in C35. CONCLUSION: C35 functions as an oncogene in breast cancer cell lines. Drug targeting of C35 or Syk kinase might be helpful in treating a subset of patients with HER2-amplified breast cancers.
Subject(s)
Breast Neoplasms/genetics , Genes, erbB-2 , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor, ErbB-2/genetics , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antigens, CD , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cadherins/genetics , Cell Line, Tumor , Colony-Forming Units Assay , DNA Primers , Down-Regulation , Female , Gene Amplification , Humans , Immunohistochemistry , Neoplasm Proteins/genetics , Oligonucleotide Array Sequence Analysis , Open Reading Frames , RNA, Messenger/genetics , Receptor, ErbB-2/antagonists & inhibitors , Receptor, ErbB-2/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Syk Kinase , Transfection , TrastuzumabABSTRACT
A 25-year-old man presented to the Emergency department in a rural South African hospital after a left, submental neck stab with a knife. Examination was deemed unremarkable, and the patient was discharged, but re-attended 2 days later complaining of a painful, swollen neck. Further examination identified Horner's syndrome, and further investigation revealed that the blade of the knife had remained in the patient's neck. This was successfully removed in theatre. This case illustrates the importance of careful history, examination and diagnostic imaging in the management of penetrating neck injuries. Horner's syndrome can be easily missed in a busy Emergency department and may indicate life-threatening pathology in the context of neck trauma. The difficulties in assessing and managing this type of injury are discussed.
