ABSTRACT
Homeobox (HOX) genes encode proteins that function as transcription factors during embryogenesis and tumorigenesis. We have previously reported upregulation of HOXC10 in gastric cancer (GC) tissues using cDNA microarray analysis. Though the functional role of HOXC10 in GC has been briefly reported, its specific mechanism is not fully understood. We analyzed the expression of HOXC10 in GC tissues, as well as its correlation with the survival outcome. By in vitro and in vivo assays, we further investigated the role of HOXC10 on cell cycle control and proliferation. Finally, we screened potential downstream targets of HOXC10 by cDNA microarray and explored the role of HOXC10 in p21 transcriptional repression through a dual luciferase reporter and chromatin immunoprecipitation. We illustrated the upregulation of HOXC10 in GC tissues and high HOXC10 expression related to poor survival outcome. Multivariable COX regression analysis showed that HOXC10 was an independent predictor of survival (HR=1.863; 95% CI: 1.076-3.225). Functionally, HOXC10 could promote GC cell proliferation and tumor growth in nude mice. Overexpression of HOXC10 accelerated G1/S cell cycle transition, whereas knocking down HOXC10 induced cell cycle arrest at the G1 phase. Critical factors of G1/S cell cycle transition including p21, CDK2, and c-Myc, were regulated by HOXC10. Importantly, an inverse correlation between p21 and HOXC10 expression in GC cell lines and tissues was observed. HOXC10 could directly bind to the promoter region of p21 and repress its transcriptional activity. Collectively, we identified HOXC10 as a predictor of poor prognosis in GC patients, and a novel transcriptional regulator of p21 in the G1/S cell cycle transition.
Subject(s)
Genes, Homeobox , Homeodomain Proteins , Stomach Neoplasms , Animals , Mice , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Mice, Nude , Stomach Neoplasms/pathology , HumansABSTRACT
We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient's condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in mainland China. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.
Subject(s)
Klebsiella Infections/microbiology , Klebsiella pneumoniae/pathogenicity , Liver Abscess/microbiology , Meningitis, Bacterial/microbiology , Shock, Septic/microbiology , Anti-Bacterial Agents/therapeutic use , Bacteriological Techniques , China , Disease Progression , Drainage , Fatal Outcome , Female , Humans , Klebsiella Infections/diagnosis , Klebsiella Infections/therapy , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/isolation & purification , Liver Abscess/diagnosis , Liver Abscess/therapy , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/therapy , Middle Aged , Shock, Septic/diagnosis , Shock, Septic/therapy , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
OBJECTIVE: To summarize the current evidence on the biomarkers associated with DNA methylation in the screening and diagnosis of colorectal cancer (CRC). METHODS: A literature search was conducted on the databases of PubMed and Web of Science to identify articles published from 1 January 2000 to 6 June 2015 with language striction. Stuides focusing on the association between noninvasive biomarkers indicating DNA methylation and CRC were included. RESULTS: Altogether 74 studies were finally included in the study. Varied genetic markers in the feces and blood samples were hypermethylated in patients with CRC than in the healthy controls. Some of them could even be detected at the early stage of the tumors. The sensitivity of the genetic markers was superior to that of fecal occult blood test and carcinoembryonic antigen. Multitarget DNA assays using a combination of different methylated genes could improve the diagnostic sensitivity. CONCLUSIONS: Genetic markers might be minimally invasive, economical and accurate for the screening and surveillance of CRC. Large multicenter studies evaluating these biomarkers systematically and prospectively not only in CRC but also in other types of cancers are needed in the future.
