Loss of heterozygosity of DPC4 tumor suppressor gene in human sporadic colon cancer

We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer. Thirty-six cases of human sporadic colon carcinoma and corresponding normal tissue samples were examined to evaluate loss of heterozygosity at the DPC4 tumor suppressor locus using variable nucleotide tandem repeat (VNTR) analysis and three polymorphic markers. From 36 analyzed samples 35 (97%) were heterozygous or informative. Loss of heterozygosity at the DPC4 locus was detected in 18 (51%) of informative tumor DNAs. The DPC4 LOH was more frequent in smaller tumors (<5 cm) than in larger ones. There was no correlation between DPC4 LOH and age or sex of patients. There was a negative correlation between DPC4 LOH and histological grade or Dukes' stage of tumors, but without statistic significance. Observed results are in agreement with the view that malignant progression is consequence of many genetic changes. It can be concluded that inactivation of the DPC4 gene plays a role in a multistep process of outgrowth and progression of colon cancer.     

Recent advances in molecular genetics of breast cancer

Breast cancer is among the most common tumors affecting women. It is characterized by a number of genetic aberrations. Some 5-10% of cases are thought to be inherited. The hereditary breast and ovarian cancer syndrome includes genetic alterations of various susceptibility genes, particularly BRCA1 and BRCA2. Breast tumors of patients with germ-line mutations in the BRCA1 and BRCA2 genes have more genetic defects than sporadic breast tumors. Here we review new findings in the function of BRCA1 gene function. Accumulation of somatic genetic changes during tumor progression map follows a specific and more aggressive pathway of chromosome damage in these individuals. A major BRCA1 downstream target gene is the DNA damage-responsive gene GADD45. Induction of BRCA1 triggers apoptosis by activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). BRCA1 interacts with SWI/SNF, a chromatin remodeling complex important in gene expression. Recent advances in genomics and bioinformatics, particularly in DNA-sequencing approaches and DNA-chip technology are expected to improve identification of small molecules, which might be drugable targets. New knowledge about the genetic portrait of breast tumor is coming from differential gene expression profiling using microarrays. Human genome studies, as well as development of "DNA chips," provide a window for observing patterns of gene activity in cells, which will contribute to more accurate cancer classification. However, substantial work connected with analytical and statistical tools must still be carried out to confirm the function of differentially expressed genes. Knowledge of the molecular characteristics of breast tumor has already started to make possible the identification of breast cancer patients who could benefit from therapies that target those features. Progress in basic research into signaling provides the opportunity to attack at least some signal-transduction targets involved in proliferation, survival, invasion, angiogenesis, metastasis, and resistance. Exciting knowledge in breast cancer biology is rapidly accumulating in parallel with recent developments in rational selection and validation of relevant targets that provide unique opportunities for development of "intelligent" therapeutics.     

Validation of the Croatian version of the Oswestry Disability Index

Purpose

To translate, cross-culturally adapt, and validate the Croatian version of the Oswestry Disability Index (ODI).

Methods

The original English-language ODI was cross-culturally adapted into Croatian and then evaluated in a group of 114 patients with chronic low back pain (LBP) at the Department of Neurosurgery, Zagreb University School of Medicine. Confirmatory factor analysis (CFA) was conducted with three models: two were theory driven (unidimensional and two dimensional—static and dynamic factors); the other was based on our exploratory factor analysis (EFA). Internal consistency and test–retest reliability were evaluated using Cronbach’s α and the intraclass correlation coefficient (ICC), respectively. Construct validity was assessed by evaluating the correlation between the ODI and Visual Analogue Scale (VAS), and between the ODI and 36-item short form survey (SF-36) scores.

Results

The EFA-derived two-dimensional structure explained 82.7% of the total variance and was significantly better than the other models (P?<?0.001); however, none of the models had acceptable fit. Internal consistency (Cronbach α?=?0.84) and test–retest reliability (ICC?=?0.94) were satisfactory. The ODI was positively correlated with VAS (r_s?=?0.54, P?<?0.001) and negatively correlated with all of the SF-36 sections (r_s?=???0.35 to ??0.64, P?<?0.001, all), apart from the role-physical (r_s?=???0.02, P?=?0.767).

Conclusions

The Croatian version of the ODI has acceptable psychometric properties. It appears to be suitable for assessment of LBP and treatment outcomes in Croatian-speaking patients. Overall, there was no evidence to reject the original unidimensional structure in favor of a two-factor solution. As such, the unidimensional structure should continue to be used in future studies.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis

The objective of this report is to explore the balance between serum and synovial fluid levels of interleukin (IL)-18 in children with juvenile idiopathic arthritis (JIA). Blood samples were obtained from 81 children with JIA and 18 control children. Synovial fluid samples were collected from 16 children with oligoarticular JIA. Concentrations of IL-18 were determined using commercial kit. Patients with systemic JIA had higher serum levels of IL-18 than patients with other forms of JIA or control children, both during the active (median, range: 6,240, 1,600–78,750 pg/ml) and inactive (1,615, 513–3,270 pg/ml) phase of disease [analysis of variance (ANOVA), P < 0.05). Levels of IL-18 in sera of children with oligoarticular JIA (255, 89–4,342 pg/ml) were similar to the respective synovial fluid levels (217, 89–1,245 pg/ml). Serum levels of IL-18 were proportional to the erythrocyte sedimentation rate and levels of C-reactive protein, but inversely proportional to the haemoglobin levels. IL-18 appears to be an important mediator of systemic JIA, while it seems of a lesser relevance in pathogenesis of other JIA forms. Therefore, inhibition of IL-18 might be a base for a successful biological therapy for systemic JIA.     

Early fibrobronchoscopy and the microbial flora composition of bronchoalveolar lavage fluid in patients with concomitant injury during treatment in intensive care units

Resuscitative bronchofibroscopy in victims with severe injury and aspiration has been shown to be both a method for diagnosing damages to the bronchus and lung and that for recovering airway patency in them. The most common involvement (47% of cases) in chest injury has been noted to be the lower lung with the development of pyoinflammatory processes caused by etiologically significant microorganisms, such as Staphylococcus aureus and types of Enterobacteriacea, in most cases (more than 50%).     

Initial experience with prophylactic Proteus vaccine immunization in an emergency clinic

As early as the first 24 hours since a severe isolated locomotor trauma the patients were immunized with Proteus vaccine. Such vaccination is shown to stimulate the production of serum specific antibodies, to reduce contamination of the wound with gram-negative agents, to shorten hospital stay and healing of the wound versus subjects vaccinated with staphylococcal anatoxin and nonimmunized patients.     

Expression of erbB-3 protein in colorectal adenocarcinoma: correlation with poor survival

Background/aims: The family of erbB receptors includes four transmembrane glycoproteins with tyrosine kinase activity. These receptors are widely expressed in normal tissues, but they also have been implicated in the development of several human adenocarcinomas. c-erbB-3/HER-3 has been detected to a greater or lesser extent in many tissues from the digestive, urinary, reproductive and respiratory tracts. The overexpression of c-erbB-3/HER-3 protein has also been shown in 53%–88% of colorectal adenocarcinomas. In this study we investigated the expression of the c-erbB-3/HER-3 gene product in colorectal tumour samples, and compared the results obtained with several clinicopathological parameters, including the survival of patients. Methods: Paraffin-embedded tissue sections were analysed immunohistochemically, using monoclonal antibody RTJ1 to human erbB-3 protein. Antibody RTJ1 specificity was confirmed by immunoprecipitation followed by Western blotting analysis. Amplification of the erbB-3 oncogene was tested by dot-blot hybridization. Results: Adenocarcinomas of the colon were positive for erbB-3 protein in 78% of samples examined. Dot-blot analysis showed no amplification of the erbB-3 gene in colon adenocarcinomas. Statistical analysis showed that patients with tumours that could not be stained for erbB-3 protein survived significantly longer (P < 0.05) than patients with tumours staining positive for the erbB-3 protein. A Cox proportional-hazards model with stepwise variable selection identified age, sex and erbB-3 expression as important prognostic factors. Conclusion: These findings demonstrate that erbB-3 protein expression could serve as a prognostic factor in colorectal malignancies. Received: 7 August 1999 / Accepted: 8 November 1999