Loss of RhoB expression in human lung cancer progression.

PURPOSE: RhoB is a low molecular weight GTPase belonging to the Ras protein superfamily. Whereas most Rho proteins have been shown to have a positive role in proliferation and malignant transformation, the specific role of RhoB appears more divergent. We reported previously that RhoB inhibits cell proliferation in various human cancer cells. Here, we studied the specific role played by RhoB in human lung cancer. EXPERIMENTAL DESIGN: We analyzed the expression of RhoB protein by immunostaining in human lung tissues ranging from normal to invasive carcinoma from different histological types in two large independent studies of, respectively, 94 and 45 samples. We then studied the cellular effect of RhoB overexpression in a model of lung cancer (A549, adenocarcinoma) and tumorigenicity in nude mice. RESULTS: We showed in both studies that RhoB protein was expressed in normal lung and decreased dramatically through lung cancer progression (P < 0.01). Interestingly, RhoB expression was lost in 96% of invasive tumors and reduced by 86% in poorly differentiated tumors compared with the nonneoplastic epithelium. Moreover, the loss of expression of RhoB correlated significantly with tumor stage and proliferative index, whereas no correlation was found between RhoB and p53 or Bcl-2 expression. We then showed that ectopic expression of RhoB in lung cancer cell line A549 suppressed cell proliferation, anchorage-independent growth, and xenograft tumor growth in nude mice. CONCLUSIONS: RhoB loss of expression occurs very frequently in lung carcinogenesis, reinforcing its putative tumor suppressive activity, and raising the value of its potential use in cancer therapy.     

Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: identification and characterization using proteomic profiling and mass spectrometry.

PURPOSE: The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays. Experimental Design: Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens. RESULTS: Using surface enhanced laser desorption and ionization, we found a serum biomarker at approximately 11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. ELISA indicated that Hp-alpha was 相似文献   

TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

Background  

Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive.     

Association of Pre-S/S and Polymerase Mutations with Acute and Chronic Hepatitis B Virus Infections in Patients from Rio de Janeiro,Brazil

Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.     

Resin infiltration of deproteinised natural occlusal subsurface lesions improves initial quality of fissure sealing

The aim of this ex vivo study was to evaluate the infiltration capability and rate of microleakage of a low-viscous resin infiltrant combined with a flowable composite resin (RI/CR) when used with deproteinised and etched occlusal subsurface lesions (International Caries Detection and Assessment System code 2). This combined treatment procedure was compared with the exclusive use of flowable composite resin (CR) for fissure sealing. Twenty premolars and 20 molars revealing non-cavitated occlusal carious lesions were randomly divided into two groups and were meticulously cleaned and deproteinised using NaOCl (2%). After etching with HCl (15%), 10 premolar and 10 molar lesions were infiltrated (Icon/DMG; rhodamine B isothiocyanate (RITC)-labelled) followed by fissure sealing (G-?nial Flo/GC; experimental group, RI/CR). In the control group (CR), the carious fissures were only sealed. Specimens were cut perpendicular to the occlusal surface and through the area of the highest demineralisation (DIAGNOdent pen, KaVo). Using confocal laser-scanning microscopy, the specimens were assessed with regard to the percentage of caries infiltration, marginal adaption and internal integrity. Within the CR group, the carious lesions were not infiltrated. Both premolar (57.9%± 23.1%) and molar lesions (35.3%± 22.1%) of the RI/CR group were uniformly infiltrated to a substantial extent, albeit with significant differences (P=0.034). Moreover, microleakage (n=1) and the occurrence of voids (n=2) were reduced in the RI/CR group compared with the CR group (5 and 17 specimens, respectively). The RI/CR approach increases the initial quality of fissure sealing and is recommended for the clinical control of occlusal caries.     

Surgical management of early pregnancy failure: history, politics, and safe, cost-effective care

Early pregnancy failure and induced abortion are often managed differently, even though safe uterine evacuation is the goal in both. Early pregnancy failure is commonly treated by curettage in operating room settings in anesthetized patients. Induced abortion is most commonly managed by office vacuum aspiration in awake or sedated patients. Medical evidence does not support routine operating room management of early pregnancy failure. This commentary reviews historical origins of these different care standards, explores political factors responsible for their perpetuation, and uses experience at University of Michigan to dramatize the ways in which history, politics, and biomedicine intersect to produce patient care. The University of Michigan initiated office uterine evacuations for early pregnancy failure treatment. Patients previously went to the operating room. These changes required faculty, staff, and resident education. Our efforts blurred the lines between spontaneous and induced abortion management, improved patient care and better utilized hospital resources.     

The levonorgestrel-releasing intrauterine system: an updated review of the contraceptive and noncontraceptive uses

The levonorgestrel containing intrauterine system is an effective and safe form of long-term yet reversible birth control. Intrauterine contraception use in the United States fell dramatically after early studies reported an association between intrauterine contraception use and later tubal infertility. Subsequent evaluation suggests that these early studies were biased. Users often experience menstrual disturbances. Informing patients of these common side effects is important to improve compliance. In addition to its contraceptive effect, the levonorgestrel intrauterine system offers potential therapeutic benefits in other clinical contexts, including menorrhagia, symptomatic fibroids, endometriosis, and endometrial suppression.     

A standardised ultrasonic diagnosis and an accurate prevalence for the retroverted uterus in general gynaecology patients

Transvaginal ultrasound with an empty bladder is recommended as a standardised ultrasonic technique for the accurate diagnosis of the retroverted uterus. Using this method, the prevalence of the retroverted uterus in 480 general gynaecological patients attending for subspecialist gynaecological ultrasound was 18%. The anteverting effect of the full bladder required for transabdominal ultrasound reduces the prevalence of the retroverted uterus to 13% (P < 0.001).