ABSTRACT
PURPOSE: c-Met is an attractive potential target for novel therapeutic inhibition of human cancer, and c-Met tyrosine kinase inhibitors (TKIs) are effective growth inhibitors of various malignancies. However, their mechanisms in anticancer effects are not clear. In the present study, we investigated the possibility that blocking c-Met signaling induces p53-mediated growth inhibition in lung cancer. MATERIALS AND METHODS: The growth inhibitory effects of c-Met TKI (SU11274) on lung cancer cells and a xenograft model were assessed using the MTT assay, flow cytometry, and terminal deoxyribonucleotide transferase-mediated nick-end labeling staining. The role of p53 protein in the sensitivity of c-Met TKI (SU11274) was examined by Western blot analysis and immunohistochemistry. RESULTS: SU11274 significantly induced apoptosis in A549 cells with wild-type p53, compared with that in Calu-1 cells with null-type p53. SU11274 increased p53 protein by enhancing the stability of p53 protein. Increased p53 protein by SU11274 induced up-regulation of Bax and PUMA expression and down-regulation of Bcl-2 expression, subsequently activating caspase 3. In p53 knock-out and knock-in systems, we confirmed that SU11274 caused apoptosis through the p53-mediated apoptotic pathway. Likewise, in the A549 xenograft model, SU11274 effectively shrank tumor volume and induced apoptosis via increased p53 protein expression. Blocking c-Met signaling increased the level of p53 protein. CONCLUSION: Our finding suggested that p53 plays an important role in SU11274-induced apoptosis, and p53 status seems to be related to the sensitivity to SU11274 in lung cancer.
Subject(s)
Humans , Apoptosis , Blotting, Western , Caspase 3 , Down-Regulation , Flow Cytometry , Growth Inhibitors , Indoles , Lung , Lung Neoplasms , Molecular Targeted Therapy , Piperazines , Protein-Tyrosine Kinases , Puma , Sulfonamides , Transplantation, Heterologous , Tumor Burden , Tumor Suppressor Protein p53 , Up-RegulationABSTRACT
Subject(s)
Animals , Humans , Rabbits , Bone Marrow , Bone Regeneration , Calcium Phosphates , Fibrin , Osteogenesis , Platelet-Rich Plasma , Skull , TransplantsABSTRACT
Hepatic cysts are the most common extrarenal manifestations of adult polycystic kidney disease, but the hepatic cyst infection in a patient with polycystic kidney disease is rare. The infection may remain localized or may be followed by acute cholangitis or septicemia. The best management for infected hepatic cyst is drainage in combination with antibiotic therapy. We experienced a case of infected hepatic cyst in a patient with polycystic kidney disease in a 46-year-old man receiving hemodialysis. He presented with fever and abdominal pain and was found to have an infected liver cyst. Treatment with antibiotics and percutaneous drainage of the cyst resulted in clinical improvement. Thus, we report a case of infected hepatic cyst in a patient with polycystic kidney disease with review of the literature.
Subject(s)
Adult , Humans , Middle Aged , Abdominal Pain , Anti-Bacterial Agents , Cholangitis , Drainage , Fever , Liver , Polycystic Kidney Diseases , Polycystic Kidney, Autosomal Dominant , Renal Dialysis , SepsisABSTRACT
A 52-year-old woman was presented with 2-week history of increasing dyspnea and dry cough. The chest radiograph revealed bilateral reticular infiltrates. Radiographic infiltrates were rapidly progressed and symptoms from hypoxemia were aggravated. The patient was intubated and bronchoscopy with transbronchial lung biopsies was performed. Biopsies revealed lymphatic vessels plugged by nests of metastatic adenocarcinoma. She died 11 days after admission despite of intensive ventilatory support. We had difficulties in the diagnosis of lymphangitic lung carcinomatosis at initial presentation of her illness because the progression was unusually rapid. Lymphangitic lung carcinomatosis should be included in the differential diagnosis of patients showing rapidly progressive interstitial radiographic findings. Also, transbronchial lung biopsy may be a useful tool to confirm the diagnosis.
Subject(s)
Female , Humans , Middle Aged , Adenocarcinoma , Hypoxia , Biopsy , Bronchoscopy , Carcinoma , Cough , Diagnosis , Diagnosis, Differential , Dyspnea , Lung , Lymphatic Vessels , Radiography, ThoracicABSTRACT
T-cell lymphoma is heterogeneous with respect to clinical presentation, course, and morphology, but it is rarely associated with sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Syndrome). We report a case of T-cell lymphoma with Rosai-Dorfman Syndrome like feature in a 31-years-old woman who presented severe non-immune hemolytic anemia and massive retroperitoneal and cervical lymphadenopathy. Her cervical lymph node biopsy revealed histiocytic infiltration showing erythrophagocytosis without marked fibrosis in the capsular and pericapsular areas and distension of sinusoids. After 6 cycles of CHOP (Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) chemotherapy, cervical and retroperitoneal lymphadenopathy was completely disappeared and according to the resolution of lymphadenopathy hemolytic anemia was also improved.
Subject(s)
Female , Humans , Anemia, Hemolytic , Biopsy , Doxorubicin , Drug Therapy , Fibrosis , Histiocytosis, Sinus , Lymph Nodes , Lymphatic Diseases , Lymphoma, T-Cell , T-Lymphocytes , VincristineABSTRACT
We report a case of insufficiency fracture of the sternum in a 70-year-old female patient with a review of the literature. She complained of sudden onset chest pain and aggravating dyspnea. She has been managed with corticosteroid due to chronic obstructive pulmonary disease for 15 years. Diagnosis of sternal insufficiency fracture presented with thoracic kyphosis was made on the basis of absence of trauma history, radiologic findings of lateral chest radiograph, bone scintigraphy and chest computed tomography. Thoracic kyphosis and osteoporosis secondary to menopause, corticosteroid therapy and limited mobility due to chronic obstructive pulmonary disease were considered as predisposing factors of the sternal insufficiency fracture in this patient.
Subject(s)
Aged , Female , Humans , Fractures, Spontaneous/diagnostic imaging , Fractures, Spontaneous/diagnosis , Fractures, Spontaneous/complications , Kyphosis/complications , Lung Diseases, Obstructive/complications , Osteoporosis, Postmenopausal/complications , Sternum/diagnostic imaging , Sternum/injuriesABSTRACT
We report a case of 46-year-old women who suffered from delayed transfusion hemolytic anemia due to anti-Jkb antibody after renal transplantation. The patient had been treated with hemodialysis and had a past history of multiple transfusion. On the second postoperative day, she received 2 units of packed red cell. During transfusion, she complained of mild chest tightness only, but 10 days later, anemia of unknown origin developed. Irregular antibody was found in her serum and identified as anti- Jkb antibody. Together with other serologic findings, she was diagnosed as delayed hemolytic transfusion reaction due to anti -Jkb antibody. We thought that this reaction might be the amnestic response to previous exposure during delivery or remote multiple transfusion. Our patient responded to steroid and plasmapheresis and recovered without severe hemolytic transfusion reaction. In conclusion, antibody screening tests and identification test might be considered as a routine pretransfusion test for all renal recipients for safe transfusion practices.
Subject(s)
Female , Humans , Middle Aged , Anemia , Anemia, Hemolytic , Blood Group Incompatibility , Kidney Transplantation , Mass Screening , Plasmapheresis , Renal Dialysis , Thorax , TransplantationABSTRACT
Flexible fiberoptic bronchoscopy is a useful tool for the diagnosis and management for diseases of the airway. Although it has been known to be a relatively safe procedure; in some cases, mild complications can occur after fiberoptlc bronchoscopy. However, fatal complications such as bacteremia, pneumonia, myocardial infarction, severe obstruction of the airways, respiratory failure or death have been reported. Among them, infectious complications following flexible fiberoptic bronchoscopy occur sometimes, although most of them are self-limited. We recently experienced a case of severe Klebsiella pneumoniae pneumonia in a patient presenting with fever following flexible fiberoptic bronchoscopy, We report this case to discuss the potential complications of fiberoptic bronchoscopy with a review of literature.
Subject(s)
Humans , Bacteremia , Bronchoscopy , Diagnosis , Fever , Klebsiella pneumoniae , Klebsiella , Myocardial Infarction , Pneumonia , Respiratory InsufficiencyABSTRACT
The combined diagnostic modalities using abdominal ultrasound, endoscopic ultrasound and endascopic retrograde cholangiopancreatogram are useful for the diagnosis of gall bladder disease. But, these diagnostic methods have limitations for the detection of early flat-type gallbladder cancer. To cope with these problems, double contrast study of gallbladder disease is being recently used to diagnose the flat-type cancer of gallbladder in Japan. Herein we report a case of chronic cholecystitis confirmed histologically and assisted by double contrast method of gallbladder, which was diagnosed as a gallbladder polyp by abdominal sonogram at first. The method requires the cystic duct cannulation and placement of the catheter to the gallbladder. And then Barium sulfate and CO2 are injected through the catheter. The patient didnt experience any complication during and after this procedure except for hyperamylasemia. After the simple cholecystectomy, he improved completely. In conclusion, double contrast study of gallbladder can be useful in the diagnosis of the gallbladder disease and compensate for the other dignostic tools.