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1.
Epidemiol Infect ; 145(11): 2269-2279, 2017 08.
Article in English | MEDLINE | ID: mdl-28629484

ABSTRACT

Mycobacterium marinum, a bacterium found in freshwater and saltwater, can infect persons with direct exposure to fish or aquariums. During December 2013, the New York City Department of Health and Mental Hygiene learned of four suspected or confirmed M. marinum skin or soft tissue infections (SSTIs) among persons who purchased whole fish from Chinese markets. Ninety-eight case-patients with non-tuberculous mycobacteria (NTM) SSTIs were identified with onset June 2013-March 2014. Of these, 77 (79%) were female. The median age was 62 years (range 30-91). Whole genome sequencing of clinical isolates revealed two main clusters and marked genetic diversity. Environmental samples from distributors yielded NTM though not M. marinum. We compared 56 case-patients with 185 control subjects who shopped in Chinese markets, frequency-matched by age group and sex. Risk factors for infection included skin injury to the finger or hand (odds ratio [OR]: 15·5; 95% confidence interval [CI]: 6·9-37·3), hand injury while preparing fish or seafood (OR 8·3; 95% CI 3·8-19·1), and purchasing tilapia (OR 3·6; 95% CI 1·1-13·9) or whiting (OR 2·7; 95% CI 1·1-6·6). A definitive environmental outbreak source was not identified.


Subject(s)
Disease Outbreaks , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium marinum/isolation & purification , Skin Diseases, Bacterial/epidemiology , Soft Tissue Infections/epidemiology , Adult , Aged , Aged, 80 and over , Animals , Case-Control Studies , Female , Fishes , Humans , Incidence , Male , Middle Aged , Mycobacterium Infections, Nontuberculous/microbiology , New York City/epidemiology , Skin Diseases, Bacterial/microbiology , Soft Tissue Infections/microbiology
2.
Gene Ther ; 22(4): 305-15, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25588741

ABSTRACT

Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor-selective replication of oncolytic adenoviruses may be hindered by oxygen deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus, retaining its antitumor activity even in a hypoxic environment. We have previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven by nine copies of the Oct4 response element (ORE) for specifically killing Oct4-overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual-regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2α and Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF-2α was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells, while sparing normal cells. AdLCY exerted potent antitumor effects in mice bearing human bladder tumor xenografts and syngeneic bladder tumors. It could target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4 is expressed in various cancers, AdLCY may be further explored as a broad-spectrum anticancer agent.


Subject(s)
Antineoplastic Agents/metabolism , Octamer Transcription Factor-3/metabolism , Oncolytic Viruses/metabolism , Urinary Bladder Neoplasms/metabolism , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Hypoxia , Cell Line, Tumor , Heterografts , Humans , Mice
3.
Gene Ther ; 21(3): 309-16, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24451116

ABSTRACT

Salmonella have been demonstrated to inhibit tumor growth. However, the mechanism of Salmonella-induced tumor cell death is less defined. Autophagy is a cellular process that mediates the degradation of long-lived proteins and unwanted organelles in the cytosol. Tumor cells frequently display lower levels of basal autophagic activity than their normal counterparts and fail to increase autophagic activity in response to stresses. Autophagy is involved in the cell defense elimination of bacteria. The signaling pathways leading to activation of Salmonella-induced autophagy in tumor cells remain to be elucidated. We used autophagy inhibitor (3-Methyladenine) and apoptosis inhibitor (Z-VAD-FMK) to demonstrate that Salmonella may induce cell death via apoptosis and autophagic pathway. Meanwhile, we suggested that Salmonella induce autophagy in a dose- and time-dependent manner. The autophagic markers were increased after tumor cell infected with Salmonella. In addition, the protein express levels of phosph-protein kinase B (P-AKT), phosph-mammalian targets of rapamycin (P-mTOR), phosph-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased by western analysis after Salmonella infection. In conclusion, our results point out that Salmonella induce the autophagic signaling pathway via downregulation of AKT/mTOR pathway. Herein, our findings that Salmonella in controlling tumor growth may induce autophagic signal pathway.


Subject(s)
Apoptosis , Autophagy , Biological Therapy , Melanoma/therapy , Salmonella enterica/pathogenicity , Animals , Melanoma/metabolism , Melanoma/microbiology , Mice , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Ribosomal Protein S6 Kinases, 70-kDa/genetics , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism
4.
Osteoarthritis Cartilage ; 19(6): 728-36, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21376128

ABSTRACT

OBJECTIVE: Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein (MIP-1γ), on the progression of OA. DESIGN: Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4(+) T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. RESULTS: The number of CD4(+) T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4(+) T cells was evident at the later stage. The activation of CD4(+) T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4(+) T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4(+) T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4(+) T cell knockout (CD4(-/-)) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. CONCLUSIONS: CD4(+) T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4(+) T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.


Subject(s)
Macrophage Inflammatory Proteins/metabolism , Osteoarthritis, Knee/immunology , Osteoarthritis, Knee/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Animals , Disease Progression , Flow Cytometry , Immunohistochemistry , Mice , NF-kappa B/metabolism
5.
Cancer Gene Ther ; 15(8): 526-34, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18497852

ABSTRACT

Cervical cancer is the second most common type of malignant tumor among women worldwide. When the disease is confined locally, it can be controlled with surgical resection and radiotherapy. However, patients with recurrent or metastatic disease often have a poor prognosis. Measurement of serum levels of squamous cell carcinoma (SCC) antigens has been widely used as serological markers for SCC of uterine cervix. Recently, it has been demonstrated that cervical cancer patients with elevated squamous cell carcinoma antigen-2 (SCCA2) expression in tumor cells carry a poor prognosis. Here, by using a luciferase reporter assay, we show that SCCA2 promoter was active in SCCA2-producing human cervical cancer cell lines, including Cx, Cxwj, SiHa and HeLa cells, but relatively quiescent in normal cervical epithelial cells. We then developed a conditionally replicating adenovirus, designated Ad-KFH, under the transcriptional control of the SCCA2 promoter. This E1B-55 kDa-deleted oncolytic adenovirus replicated specifically in and lysed SCCA2-producing cervical cancer cells. Furthermore, in a peritoneal metastatic tumor model, Ad-KFH retarded Cxwj tumor growth in NOD/severe combined immunodeficient mice and prolonged survival of tumor-bearing mice, especially when combined with cisplatin. These results suggest that Ad-KFH may provide a new strategy of gene therapy for advanced or recurrent uterine cervical cancer.


Subject(s)
Adenoviridae/genetics , Adenovirus E1B Proteins/genetics , Antigens, Neoplasm/genetics , Genetic Therapy , Promoter Regions, Genetic , Serpins/genetics , Uterine Cervical Neoplasms/therapy , Virus Replication , Adenoviridae/physiology , Animals , Base Sequence , Cell Line, Tumor , DNA Primers , Female , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Reverse Transcriptase Polymerase Chain Reaction , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology
6.
Br J Cancer ; 88(9): 1492-9, 2003 May 06.
Article in English | MEDLINE | ID: mdl-12778082

ABSTRACT

Mutations or loss of heterozygosity of p53 are detected in approximately 50% of bladder cancers. E1B-55 kD-deleted adenovirus has been shown to kill tumour cells with defective p53 function while sparing normal cells. Here, we examined the cytolytic effect and replication of E1B-55 kD-deleted adenovirus, designated Ad5WS1, on human bladder cancer cell lines with various p53 status. Ad5WS1 caused more severe cytolytic effect and replicated more efficiently in J82 and TCC-SUP bladder cancer cells carrying mutant p53 compared with TSGH-8301 and BFTC-905 bladder cancer cells retaining wild-type p53. Introduction of dominant negative p53 into BFTC-905 cells rendered them more susceptible to Ad5WS1-induced cytolysis. Furthermore, cells susceptible to lysis caused by Ad5WS1 were not attributable to their greater infectability by adenovirus. Finally, Ad5WS1 suppressed the growth of TCC-SUP bladder tumour xenografts, which could be augmented when combined with replication-defective adenoviral vector encoding kringles 1-5 of plasminogen (K1-5), an angiogenic inhibitor. Taken together, our results show that E1B-55 kD-deleted adenovirus replicates and hence lyses bladder cancer cells with mutant p53 much more efficient than those with wild-type p53. Thus, E1B-deleted adenovirus may have therapeutic potential, especially in combination with adenoviral vector expressing K1-5, for the treatment of bladder cancer.


Subject(s)
Adenoviridae/genetics , Adenovirus E1B Proteins/genetics , Genetic Therapy/methods , Urinary Bladder Neoplasms/therapy , Virus Replication/physiology , Adenoviridae/physiology , Cell Survival , Gene Deletion , Humans , Recombinant Proteins , Transfection , Tumor Cells, Cultured , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/virology
7.
Zhonghua Yi Xue Za Zhi (Taipei) ; 47(3): 187-91, 1991 Mar.
Article in Chinese | MEDLINE | ID: mdl-1848147

ABSTRACT

The mortality associated with 52128 anesthetics administered over two years (1988-1989) at Mackay Memorial Hospital, Taipei, was reported. The frequency of death to which anesthesia contributed was 0.4/10000 (2 cases in 52128 anesthetics). The total mortality rate from surgery within one week was 0.2% (105 cases in 52128 anesthetics). Anesthetic deaths were responsible for 1.9% of the total mortality. There were 25 cases of cardiac arrest with 18 fatal cases (7 cases were recovered after cardiopulmonary resuscitation). The causes of cardiac arrest during anesthesia included anesthetic factors (24%), surgical factors (24%) and patients' pathological factors (52%).


Subject(s)
Anesthesia/mortality , Surgical Procedures, Operative/mortality , Anesthesia/adverse effects , Anesthesia/statistics & numerical data , Anesthetics/adverse effects , Heart Arrest/mortality , Humans , Surgical Procedures, Operative/statistics & numerical data
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