ABSTRACT
Peripheral Tcell lymphomas (PTCLs) are heterogeneous malignancies that are types of nonHodgkin lymphomas; patients with this disease have poor prognoses. The IL2inducible Tcell kinasespleen tyrosine kinase (ITKSYK) fusion gene, the first recurrent chromosome translocation in PTCLnot otherwise specified (NOS), can drive cellular transformation and the development of Tcell lymphoma in mouse models. The aim of the current study was to investigate the signal transduction pathways downstream of ITKSYK. The authors constructed a lentiviral vector to overexpress the ITKSYK fusion gene in Jurkat cells. By using SignalNet and cluster analyses of microarray data, the authors identified the tyrosineprotein kinase JAK (JAK)3/STAT5 signalling pathway as a downstream pathway of ITKSYK, activation of which mediates the effects of ITKSYK on tumourigenesis. JAK3selective inhibitor tofacitinib abrogated the phosphorylation of downstream signalling molecule STAT5, supressed cell growth, induced cell apoptosis and arrested the cell cycle at the G1/S phase in ITKSYK+ Jurkat cells. In a xenograft mouse model, tumour growth was significantly delayed by tofacitinib. Since JAK3 associates with interleukin2 receptor subunit γ (IL2RG) only, siRNAspecific knockdown of IL2RG showed the same effect as tofacitinib treatment in vitro. These results first demonstrated that the activation of the IL2RG/JAK3/STAT5 signalling pathway contributed greatly to the oncogenic progress regulated by ITKSYK, supporting further investigation of JAK3 inhibitors for the treatment of PTCLs carrying the ITKSYK fusion gene.
Subject(s)
Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Interleukin Receptor Common gamma Subunit/metabolism , Janus Kinase 3/metabolism , Lymphoma, T-Cell, Peripheral/pathology , Oncogene Proteins, Fusion/metabolism , STAT5 Transcription Factor/metabolism , Tumor Suppressor Proteins/metabolism , Animals , Apoptosis , Biomarkers, Tumor/genetics , Cell Proliferation , Female , Gene Expression Profiling , Genome, Human , Humans , Interleukin Receptor Common gamma Subunit/genetics , Janus Kinase 3/genetics , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell, Peripheral/genetics , Lymphoma, T-Cell, Peripheral/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Oncogene Proteins, Fusion/genetics , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , STAT5 Transcription Factor/genetics , Syk Kinase/genetics , Syk Kinase/metabolism , Tumor Cells, Cultured , Tumor Suppressor Proteins/genetics , Xenograft Model Antitumor AssaysABSTRACT
Pyoderma gangrenosum (PG) is a rare, noninfectious, inflammatory disease characterized by neutrophilic infiltration and destruction of tissue. Extracutaneous involvement in PG is unusual. Myelodysplastic syndrome (MDS) is the most frequent hematologic disease associated with PG. We present a case diagnosed with MDS-EB-I. He had a large ulcer in his buttocks. Tissue culture and microscopy showed no evidence of fungi, bacteria, or mycobacteria. Histology showed granulation tissue, inflammatory infiltrate, abscess formation, and focal necrotizing vasculitis. Dermatology opinion confirmed PG. The skin lesions responded well to corticosteroid treatment at first, but it relapsed quickly with involvement of skin and lungs. In the meantime, MDS progressed to acute myeloid leukemia. The patient received chemotherapy and immunosuppressive therapy at the same time. After achievement of complete remission (CR), he had allogeneic hematopoietic stem cell transplantation. Two years later, the patient is still in CR status with no sign of PG relapse.
ABSTRACT
The specimens of ductal carcinoma in situ (DCIS) with early invasion, and specimens collected by core needle biopsy (CNB) tend to contain limited amount of invasive component, so it is imperative to explore a new technique which can assess HER2 gene status accurately for the limited invasive cancer component in these specimens. Dual staining technique of combining immunohistochemistry (IHC) for myoepithelial cells and single or dual probe chromogenic in situ hybridization (CISH) for HER2 gene was performed on routinely processed paraffin sections from 20 cases diagnosed as having DCIS with invasive cancer. Among them, 10 had fluorescence in situ hybridization (FISH)-confirmed amplification of HER2 and 10 had FISH-confirmed non-amplification of HER2. We successfully detected HER2 genetic signals and myoepithelial IHC markers (SMM-HC or CK5/6) simultaneously on a single section in all 20 specimens. Myoepithelial markers and HER2 signals detected by dual staining assay were consistent with those by individual technique performed alone. HER2 gene amplification results determined by dual staining assay were 100% consistent with those of FISH. Dual staining technique which allows simultaneous detection of myoepithelial marker protein and cancerous HER2 gene is feasible, and it has potential to be used in clinical practice for effective determination of HER2 amplification in limited invasive component.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence/methods , Receptor, ErbB-2/metabolism , Breast Neoplasms/genetics , Chromogenic Compounds , Female , Gene Expression Profiling/methods , Humans , Neoplasm Invasiveness/pathology , Neoplasm Invasiveness/physiopathology , Receptor, ErbB-2/genetics , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Gastric carcinoma with osteoclast-like giant cells (OGCs) is an extremely rare tumor. So far, only six cases have been reported in the literature. Here we report an additional case of this tumor in a Chinese 78-year-old man presented with abdominal pain, vomiting, and hematemesis. Physical examination and gastroscopy revealed a tumor in the gastric antrum. The biopsy and pathological findings indicated a gastric adenocarcinoma with OGCs, which were present in both the tumor and the metastatic lymph nodes. Further immunohistochemical staining indicated that OGCs were reactive with CD68, CD45, and vimentin protein, but not with pancytokeratin, carcinoembryonic antigen, or epithelial membrane antigen, suggesting the monocytic/histiocytic derivation of these OGCs. In situ hybridization for Epstein-Barr virus showed no nuclear positivity in either adenocarcinoma or OGCs. Postoperative follow-up showed that the patient had survived for at least 6 months without recurrence. Further investigation is warranted to clearly define the prognostic significance of OGCs in gastric carcinoma.
Subject(s)
Giant Cells/pathology , Osteoclasts/pathology , Stomach Neoplasms/pathology , Aged , Giant Cells/metabolism , Humans , Immunohistochemistry , In Situ Hybridization , Male , Osteoclasts/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolismABSTRACT
AIM: To study the influence of high-frequency electric surgical knives on healing of abdominal incision. METHODS: Two hundred and forty white rats were divided into 10(0), 10(2), 10(5), and 10(8) groups and rat models of abdominal operation were induced by using electric surgical knives and common lancets respectively. Then they were respectively given hypodermic injections of normal saline and 0.2 mL quantitative mixture of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa at a concentration of 10(2), 10(5) and 10(8). On the basis of the animal experiment, 220 patients undergoing abdominal operations (above type II) were randomly allocated into one of following three groups: electric knife (EK, 93 cases), electro-coagulation (EC, 55 cases) and control (72 cases). High-frequency electric surgical knives were used to dissect abdominal tissues and electro-coagulation for hemostasis in EK group. Common lancets and electro-coagulation were applied in EC group. Common lancets and tying silk suture were used in the controls. RESULTS: In all the groups except group 10(0), infection rate of incisional wounds made by electric surgical knives were remarkably higher than that with common lancets. Furthermore, there were significant differences in groups 10(2), 10(5), and 10(8) (P<0.05), but not in group 10(0) (P>0.05) between EK and EC groups. Clinical studies showed a delayed wound healing in 16 cases (17.20%) in EK, 11 cases (16.36%) in EC and 2 cases (2.86%) in the control groups. A significant difference between EK and the control groups (chi2 = 8.57, P<0.01), and between EC and the control groups (chi2 = 5.66, P<0.05) was observed, but not between EK and EC (chi2 = 0.017, P>0.05). CONCLUSION: High-frequency electric knives may remarkably delay abdominal incision healing. Its application should be minimized so as to reduce the possibility of postoperative complications.