Murine double minute homolog 2 (MDM2) is an oncoprotein that induces p53 degradation via ubiquitin-ligase activity. MDM4 cooperates with MDM2-mediated p53 degradation, directly inhibiting p53 transcription by binding to its transactivation domain. Our previous study reported that the simultaneous inhibition of MDM2 and MDM4 using nutlin-3 (an inhibitor of the MDM2-p53 interaction) and chimeric small interfering RNA with DNA-substituted seed arms (named chiMDM2 and chiMDM4) more potently activated p53 than the MDM2 or MDM4 inhibitor alone and synergistically augmented antitumor effects in various types of cancer cells with the wild-type (wt) .
View Article and Find Full Text PDFBackground/aim: The oncoproteins murine double minute (MDM) 2 and MDM4 inactivate tumor-suppressor protein p53. Their mutual relationship with the prognosis of gastric cancer (GC) remains unknown.
Patients And Methods: Expression of MDM2, MDM4, and p53 in tumors of 241 patients with GC were evaluated immunohistochemically.
Inactivation of the TP53 tumor suppressor gene is essential during cancer development and progression. Mutations of TP53 are often missense and occur in various human cancers. In some fraction of wild-type (wt) TP53 tumors, p53 is inactivated by upregulated murine double minute homolog 2 (MDM2) and MDM4.
View Article and Find Full Text PDFMDM2 and MDM4, a structurally related MDM2 homolog, negatively regulates expression and functions of TP53 tumor suppressor gene. To explore the precise expression patterns and function of MDM2 and MDM4 in wild-type (wt) TP53 cancer cells, we analyzed 11 various cancer cell lines with wt TP53. All cell lines exhibited deregulated expression of MDM2 and MDM4, and were divided into two distinct types; the one expressing high levels of MDM4 and another expressing low levels of MDM4.
View Article and Find Full Text PDFUp-regulated sirtuin 1 (SIRT1), an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer.
View Article and Find Full Text PDFIt has been reported that upregulated SIRT1 (NAD(+)-dependent class III histone deacetylase) deacetylates the p53 protein, represses its function, and allows for tumor cell growth in various cancers. Here we investigated antitumor effects of tenovin-6, a small-molecule inhibitor of SIRT1 and SIRT2, in various colon cancer cell lines. Tenovin-6 induced apoptosis in all five colon cancer cell lines investigated (two cell lines with wild-type p53 and three with mutant p53) regardless of the p53 mutation status.
View Article and Find Full Text PDFBackground/aim: Monoclonal antibodies against epidermal growth factor receptor (EGFR) can extend progression-free survival (PFS) and overall survival (OS) in patients with unresectable colorectal cancer; however, skin toxicity often interferes with therapy continuation.
Patients And Methods: We analyzed the polymorphisms in EGFR and IgG fragment C receptor (FCGR) genes and determined their associations with clinical outcomes including PFS, OS, and skin toxicity. Five polymorphisms in EGFR and FCGR genes in 32 patients with unresectable colorectal cancer who were treated with antibodies against EGFR were examined.
Papillomavirus genomes are thought to be amplified to about 100 copies per cell soon after infection, maintained constant at this level in basal cells, and amplified for viral production upon keratinocyte differentiation. To determine the requirement for E1 in viral DNA replication at different stages, an E1-defective mutant of the human papillomavirus 16 (HPV16) genome featuring a translation termination mutation in the E1 gene was used. The ability of the mutant HPV16 genome to replicate as nuclear episomes was monitored with or without exogenous expression of E1.
View Article and Find Full Text PDFThe tumor suppressor gene p53 is the most frequently mutated gene in human cancers. However, its mutation rate is relatively low in gastric cancer compared with other cancers. In this study, we investigated the mechanisms underlying the antitumor effects of nutlin-3, an inhibitor of human homolog of murine double minute 2 (MDM2).
View Article and Find Full Text PDFWe studied the effects of Q fever in hospital-acquired pneumonia. The subjects consisted of 121 cases with hospital-acquired pneumonia treated during the period from December 2004 till June 2007. Q fever was diagnosed using a PanBio Coxiella burnetii ELISA test kit.
View Article and Find Full Text PDFWe studied the clinical effects of intravenous ciprofloxacin (CPFX) on community-acquired pneumonia in patients with positive Immunocard Mycoplasma test results. The subjects were 35 patients (59.4 +/- 24.
View Article and Find Full Text PDFShort interfering RNA (siRNA)-based RNA interference (RNAi) is widely used for target gene knockdown in mammalian cells. To clarify the position-dependent functions of ribonucleotides in siRNA, siRNAs with various DNA substitutions were constructed. The following could be simultaneously replaced with DNA without substantial loss of gene-silencing activity: the seed arm, which occupies positions 2-8 from the 5'end of the guide strand; its complementary sequence; the 5'end of the guide strand and the 3'overhang of the passenger strand.
View Article and Find Full Text PDFA 45-year-old man who had hypertension, hyperthyroidism, and bronchial asthma was admitted to our hospital because of a low-grade fever and chest pain. The physical findings and laboratory data were almost all within normal limits except for evidence of mild inflammation and liver dysfunction. The chest X-ray findings seemed normal, but a computed tomography (CT) scan showed multiple nodules in both lower lung fields.
View Article and Find Full Text PDFNihon Kokyuki Gakkai Zasshi
October 2007
We evaluated the clinical features of multidrug-resistant Pseudomonas aeruginosa cases determined by sputum culture between April, 2005 and December, 2006. The clinical features of most cases were: (1) pneumonia in the elderly with cerebrovascular diseases, (2) previous administration of carbapenems and antipseudomonal cephems, (3) PIPC, CAZ and ISP sensitve MDRP, (4) MRSA was isolated concurrently, (5) not necessary of therapy against MDRP, (6) good outcome.
View Article and Find Full Text PDFPurpose: We reported previously that reactive oxygen species (ROS) are key mediators of apoptosis induced by a polyphenol, (-)-epigallocatechin-3-gallate (EGCG), in myeloid leukemic cells. This study aimed to further examine the mechanism of ROS-mediated apoptosis induced by EGCG and its relationship to the heme enzyme myeloperoxidase (MPO).
Experimental Design: We established stably transfected K562 cells expressing wild-type and mutant MPO.
We evaluated the positive phase period of ImmunoCard Mycoplasma tests. The subjects were 74 penumonia patients (male : 38, female : 36, 17-94 years old) with positive ImmunoCard Mycoplasma tests. ImmunoCard Mycoplasma tests were performed every week for 8 weeks later, then every 4 weeks until negative conversion.
View Article and Find Full Text PDFThe aim of the present study was to determine the incidence of Q fever in patients with an acute exacerbation of a chronic lower respiratory tract infection. Eighty patients treated for acute exacerbation of chronic lower respiratory tract infections during a 30-month period were studied. Q fever was diagnosed by ELISA.
View Article and Find Full Text PDFNihon Kokyuki Gakkai Zasshi
March 2007
We evaluated the effectiveness of ImmunoCard Mycoplasma rapid tests in all patients admitted with community-acquired pneumonia (CAP) between January, 2004 and December, 2005. ImmunoCard Mycoplasma rapid tests were performed on the 1st day of admission and we analyzed the frequency of positive cases among CAP cases according to month and age. A total of 82 of 270 (33.
View Article and Find Full Text PDFWe demonstrated here for the first time that zerumbone (ZER), a natural cyclic sesquiterpene, significantly suppressed the proliferation of promyelocytic leukemia NB4 cells among several leukemia cell lines, but not human umbilical vein endothelial cells (HUVECs), by inducing G2/M cell cycle arrest followed by apoptosis with 10 microM of IC50. Treatment of NB4 cells with growth-suppressive concentrations of ZER resulted in G2/M cell cycle arrest that was associated with a decline of Cyclin B1 protein, but with the phosphorylation of ATM/ Chk1/Chk2. In addition, ZER induced the phosphorylation of Cdc25C at the Thr48 residue and Cdc2 at the Thr14/Tyr15 residues.
View Article and Find Full Text PDFp27KIP1 is known as a regulator of cellular differentiation and apoptosis in human cancer cells. We have previously reported that human chronic myeloid leukemia (CML) KU812 and K562 cells show inhibited cellular proliferation in response to treatment with activin A, a member of TGF-beta superfamily. Apoptosis and erythroid differentiation can be induced in KU812 and K562 cells, respectively.
View Article and Find Full Text PDFNihon Kokyuki Gakkai Zasshi
June 2006
We studied the clinical effect of continuous infusion over 24 hours of meropenem (MEPM) on bacterial pneumonia in the elderly (over 65). The subjects were 26 patients (community-acquired pneumonia: moderate, n = 9; severe, n= 4; hospital-acquired pneumonia: group III, n = 13) whose performance status was 3 or 4. MEPM 1.
View Article and Find Full Text PDFObjective: To identify sensitive clinical predictors for the detection of community-acquired pneumonia in adults as a guide to when to order a CXR.
Methods: In total, 79 outpatients presenting with at least one of the following clinical features of pneumonia: fever, cough, sputum, chest pain, dyspnoea and coarse crackles and who underwent CXR to detect pneumonia were examined retrospectively. The relationship between these clinical features and the presence of pneumonia on CXR was determined.
The clinical effect of gatifloxacin (GFLX) at 200 mg daily (half of common dosage) on bacterial community-acquired pneumonia in the elderly was examined. Subjects were 30 patients with bacterial community-acquired pneumonia aged 65 years or more (mild, 21 patients; moderate, 9 patients), and GFLX at 100 mg per dose was administered twice daily for 4-14 days. The results included clinical effectiveness in 21 of 21 mildly affected patients (efficacy rate, 100%), in 8 of 9 moderately affected patients (efficacy rate, 88.
View Article and Find Full Text PDFNihon Kokyuki Gakkai Zasshi
September 2005
We studied the effect of Q fever in acute exacerbation of chronic lower respiratory tract infection. The subjects consisted of 80 cases with acute exacerbation of chronic lower respiratory tract infection treated during the period from March 2002 till October 2004. Q fever was diagnosed using a PanBio Coxiella burnetii ELISA test kit.
View Article and Find Full Text PDFJ Infect Chemother
February 2005
The effect of intravenous ciprofloxacin (CPFX) on hospital-acquired pneumonia was examined. The subjects were 32 patients with hospital-acquired pneumonia classified as being in group I, group II, and group III, based on The Japanese Respiratory Society Guidelines for management of hospital-acquired pneumonia. None of the patients had received antibiotic treatment for the pneumonia.
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