PURPOSE: Recently the theory has been developed that host genetic factor affects interleukin (IL)-1beta might exert an influence on the divergent clinical outcomes. We evaluated the roles of H. pylori infection and polymorphism of IL-1beta in the carcinogenesis of gastric adenocarcinoma. METHODS: Gastric cancer tissues from 68 patients, peripheral blood from 43 controls, and various gastric cancer cell lines (MKN45, MKN74, SNU620, SNU638, SNU216, SNU601, and AGS) were used. Single nucleotide polymorphism (SNP) of IL-1beta-31 and the length of tandem repeat of IL-1RN were analyzed by PCR and automatic DNA sequencer. IL-1beta mRNA expressions from gastric cancer tissues were measured using semiquantitative RT-PCR and compared according to SNP of IL-1beta-31. We also investigated the IL-1beta-31 SNP from various cancer cell lines and measured IL-1beta mRNA and protein expressions using semiquantitative RT- PCR and ELISA. We constructed reporter systems for IL-1beta-31T/T and IL-1beta-31C/C and the responses to antigen PMA and H. pylori were compared. RESULTS: We couldn't find any significant difference in the frequencies of IL-1beta-31 SNP and IL-1RN polymorphism between the gastric cancer and control groups. IL-1beta mRNA and protein expression were significantly more highly responsive to PMA at IL-1beta-31 T/T type as compared with those of C/T or C/C type when studied in gastric cancer cell lines, although we couldn't find any significant difference of IL-1beta mRNA expression according to IL-1beta-31 SNP when studied in gastric cancer tissue. When we compared the activities of reporter systems, the basal luciferase activity, response to PMA, and response to H. pylori of reporter genes was 1.30-fold, 1.32-fold, and 1.62-fold higher respectively in pIL-1beta T/T type as compared with pIL-1beta C/C type. CONCLUSIONS: These findings indicate that SNP of IL-1beta exerts an influence on the expression of IL-1beta and there is a significant difference in response to environmental factors. They also suggest that the host with IL-1beta-31 T/T type has a higher risk of hypochlorhydria, gastric atrophy, and after all gastric cancer in response to H. pylori infection. However the relationship between polymorphism of IL-1beta and gastric adenocarcinoma require further study.
Achlorhydria ; Adenocarcinoma ; Atrophy ; Carcinogenesis ; Cell Line ; DNA ; Enzyme-Linked Immunosorbent Assay ; Genes, Reporter ; Helicobacter pylori* ; Helicobacter* ; Humans ; Interleukin-1beta* ; Interleukins ; Luciferases ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; RNA, Messenger ; Stomach Neoplasms* ; Tandem Repeat Sequences

The diagnosis of incracranial tuberculoma in immune-compromised hosts is often difficult because conventional magnetic resonance (MR) imaging of tuberculoma reveals various findings and neurologic symptoms are not typical. Here, we report a case of a 54-yr old man with multiple intracranial tuberculoma who was treated for acute myeloid leukemia. He complained of right-side paresthesia after the third consolidation chemotherapy without leukemic relapse and fever. MR imaging of the brain showed multiple ring-enhanced lesions in the cerebrum, cerebellar hemisphere, and pons. The lesions appeared to mimic a metastatic tumor or abscess. Cerebrospinal fluid analysis showed no abnormal cells, but the level of adenosine deaminase was elevated (28.8 IU/L, normal 0-8). Stereotactic brain biopsy was performed, but only reactive gliosis was observed. To confirm diagnosis, an open brain biopsy was performed. The histopathology demonstrated chronic granulomatous inflammation with caseous necrosis. Tuberculous-polymerase chain reaction of the biopsy showed a positive result. He was treated with anti-tuberculosis medication and a high dose of steroid. Paresthesia improved, and follow-up brain MR imaging showed the decreased size and numbers of ring-enhanced lesions and improvement of perilesional edema 1 month after treatment. Here, we report on an interesting case of intracranial tuberculoma in acute myeloid leukemia.
Antitubercular Agents/therapeutic use ; Brain Neoplasms/*diagnosis ; Diagnosis, Differential ; Humans ; Leukemia, Myeloid, Acute/*complications ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Sarcoma, Myeloid/*diagnosis ; Tuberculoma, Intracranial/complications/*diagnosis/drug therapy

Clinically detectable metastatic follicular thyroid carcinoma to the thymus is very rare in the literature and sometimes confused with false positive uptake of Iodine
Adenocarcinoma, Follicular/*secondary ; Adult ; Case Report ; Female ; Human ; Iodine Radioisotopes/diagnostic use ; Thymus Neoplasms/*secondary ; Thyroid Neoplasms/*pathology/radionuclide imaging/surgery ; Tomography, Emission-Computed

PURPOSE: The goal of this study was to evaluate the clinicopathologic characteristics and to investigate the expression of p53, c-erbB2, and nm23 protein in gastric remnant cancer. MATERIALS AND METHODS: We evaluated the clinicopathologic characteristics and expression of p53, c-erbB2, and nm23 protein in 37 cases gastric remnant cancer (GRC) that detected at least 5 years after initial surgery, and compare them with adenocarcinoma from intact stomach. Twenty-seven patients among the 37 patients of GRC and 271 patients of primary gastric cancer (PGC) were chosen for immunohistochemical staining against p53, c-erbB2, and nm23. RESULTS: The median age was 59 years, male was predominant and median time interval between operations were 15 years. GRC initially operated for benign disease were detected later after initial gastrectomy and had a tendency toward lymph node metastasis than those initially operated for malignant disease. Resection was performed in 31 patients (81.0%) in whom 28 patient (71.0%) with curative intent. The overall 5-year survival rate was 44.8%. Multivariate analysis had revealed that depth of invasion was the most significant prognostic factor. p53, c-erbB2, and nm23 protein expression rates of GRC were 44.4%, 14.8%, and 66.7%, respectively and those of PGC were 45.4%, 16.2%, and 85.1%, respectively. p53 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in both GRC and PGC. p53 protein expression and depth of invasion had an inverse relationship only in GRC. c-erbB2 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in PGC. nm23 protein expression was more frequently expressed in the group of positive lymph node metastasis in GRC. CONCLUSION: Early detection by periodic endoscopic follow-up and radical resection is a reasonable treatment policy for GRC. The results of p53, c-erbB2, and nm23 expression suggest that they might have somewhat different roles in the pathogenesis and progression in GRC and PGC, so further study may be of benefit hereafter.
Adenocarcinoma ; Gastrectomy ; Gastric Stump* ; Humans ; Lymph Nodes ; Male ; Multivariate Analysis ; Neoplasm Metastasis ; Stomach ; Stomach Neoplasms ; Survival Rate

Checkpoint kinase 1 (Chk1) and Chk2 are effector kinases in the cellular DNA damage response and impairment of their function is closely related to tumorigenesis. Previous studies revealed several substrate proteins of Chk1 and Chk2, but identification of additional targets is still important in order to understand their tumor suppressor functions. In this study, we screened novel substrates for Chk1 and Chk2 using substrate target motifs determined previously by an oriented peptide library approach. The potential candidates were selected by genome-wide peptide database searches and were examined by in vitro kinase assays. ST5, HDAC5, PGC-1alpha, PP2A PR130, FANCG, GATA3, cyclin G, Rad51D and MAD1alpha were newly identified as in vitro substrates for Chk1 and/or Chk2. Among these, HDAC5 and PGC-1alpha were further analyzed to substantiate the screening results. Immunoprecipitation kinase assay of full-length proteins and site-directed mutagenesis analysis of the target motifs demonstrated that HDAC5 and PGC-1alpha were specific targets for Chk1 and/or Chk2 at least in vitro.
Amino Acid Motifs ; Amino Acid Sequence ; *Consensus Sequence ; Genome, Human/*genetics ; Heat-Shock Proteins/chemistry/metabolism ; Histone Deacetylases/chemistry/metabolism ; Humans ; Molecular Sequence Data ; Peptide Fragments/chemistry/metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Protein Kinases/*metabolism ; Protein-Serine-Threonine Kinases/*metabolism ; Substrate Specificity ; Transcription Factors/chemistry/metabolism

Dermatomyositis (DM) is an uncommon inflammatory myopathy with characteristic rash accompanying, or more often preceding, muscle weakness. There is a well-recognized association between DM and several cancers, such as ovarian cancer, breast cancer, melanoma, colon cancer, and non-Hodgkin lymphoma. We report the first case of cancer of unknown primary site associated with DM. A 62-yr-old woman presented to us with both shoulder painful swelling and facial edema. She was diagnosed previously as cancer of unknown primary site, histologically confirmed with squamous cell carcinoma in a pelvic mass. For the following days, she complained of erythematous face followed by progressive weakness of the proximal muscles of upper and lower limbs. The laboratory tests showed an increased muscle enzyme and acute phase reactants. The electromyogram showed the typical findings of DM. After the treatment with high dose steroid and methotrexate, the proximal motor weakness improved, and she received palliative radiation therapy.
Carcinoma, Squamous Cell/complications/diagnosis/pathology ; Dermatomyositis/*complications/diagnosis/pathology/therapy ; Female ; Humans ; Middle Aged ; Neoplasms, Unknown Primary/*complications/diagnosis/pathology

A study on fibronectin, which is synthesized in response to inflammatory process of joint destruction, can be of great value in identifying the mechanism of inflammation or disease activity of rheumatoid arthritis (RA). This study attempts to measure the concentrations of total fibronectin in synovial fluid of patients with RA and osteoarthritis (OA), and compare it with the clinical disease activity parameters of RA available. A total 68 patients suffering from knee pain and joint effusion was examined. Synovial fluids of thirty-eight RA patients and thirty OA patients were measured by using monoclonal fibronectin antibody. Cross-sectional analysis was undertaken to correlate the fibronectin levels of the RA patients with the clinical disease activity parameters available. RESULTS: 1. Mean synovial fibronectin level of RA (148.4+/-72.6 microgram/ml) was significantly higher than that of OA (39.5+/-16.9 microgram/ml)(p<0.001). 2. The fibronectin levels in RA do not seem to have significant relationship with the parameters such as disease duration, the duration of morning stiffness, Ritchie index, ESR, CRP, and rheumatoid factor. CONCLUSION: In conclusion, the synovial total fibronectin concentration can clearly distinguish RA from OA. However, it would be unlikely to be used as a parameter of disease activity.
Arthritis, Rheumatoid* ; Cross-Sectional Studies ; Fibronectins* ; Humans ; Inflammation ; Joints ; Knee ; Osteoarthritis ; Rheumatoid Factor ; Synovial Fluid