PubMed Health⌕ Search

Biomedical subjects

S Joos

Publications and source records attributed to S Joos.

At least 19 recordsLinked to original sources
PubMed2007

Comparison of p16(INK4a) expression with p53 alterations in head and neck cancer by tissue microarray analysis.

We investigated whether there is a relationship between loss of p16(INK4a) protein expression and p53 alterations in head and neck squamous cell carcinomas (HNSCCs). For this purpose, immunohistochemistry was performed on tissue microarrays of 664 tumours; this represents the largest HNSCC cohort studied for molecular biomarkers. Loss of p16(INK4a) protein expression was associated with aberrant p53 expression (negative or overexpressed) in the total cohort, and with TP53 mutations in 200 tumours analysed (p < 0.0001 each). Both loss of p16(INK4a) expression and p53 alterations differed significantly across both tumour sites and stages, being more prevalent in the hypopharynx than in the other tumour sites and in advanced tumour stages. As a possible link between p53 status and p16(INK4a) loss, we found that increased DNA methyltransferase 1 protein levels occurred preferentially in tumours with aberrant p53 (p = 0.001) and negative p16(INK4a) expression (p = 0.0004). In the total cohort, there was a borderline significant difference in patient survival across three p16(INK4a) expression levels (negative, positive, high), with loss of p16(INK4a) expression showing shortest survival. It is suggested that loss of p16(INK4a) expression and p53 alterations should be viewed as related events involved in the early carcinogenic process.

Carcinoma, Squamous Cell↗
PubMed2006

Expression analysis of imbalanced genes in prostate carcinoma using tissue microarrays.

To identify candidate genes relevant for prostate tumour prognosis and progression, we performed an exhaustive gene search in seven previously described genomic-profiling studies of 161 prostate tumours, and four expression profiling studies of 61 tumours. From the resulting list of candidate genes, six were selected for protein-expression analysis based on the availability of antibodies applicable to paraffinised tissue: fatty acid synthase (FASN), MYC, beta-adrenergic receptor kinase 1 (BARK1, GRK2) the catalytic subunits of protein phosphatases PP1alpha (PPP1CA) and PP2A (PPP2CB) and metastasis suppressor NM23-H1. These candidates were analysed by immunohistochemistry (IHC) on a tissue microarray containing 651 cores of primary prostate cancer samples and benign prostatic hyperplasias (BPH) from 175 patients. In univariate analysis, expression of PP1alpha (P=0.001) was found to strongly correlate with Gleason score. MYC immunostaining negatively correlated with both pT-stage and Gleason score (P<0.001 each) in univariate as well as in multivariate analysis. Furthermore, a subgroup of patients with high Gleason scores was characterised by a complete loss of BARK1 protein (P=0.023). In conclusion, our study revealed novel molecular markers of potential diagnostic and therapeutic relevance for prostate carcinoma.

Biomarkers, Tumor↗
PubMed2006

[Obsessive compulsive disorder and the internet. An evaluation of Dutch-language websites and quality indicators].

BACKGROUND: The Internet is an important source of information about health matters. The quality of the information about Obsessive Compulsive Disorder (OCD) has not been investigated. Possible indicators of quality are the DISCERN rating tool, Google PageRank and cooperation from health care professionals. AIM: To investigate the quality of the information given on Dutch-language websites relating to OCD and to determine whether the quality of the contents is correlated with site characteristics, scores on DISCERN and Google PageRank. METHOD: We selected 27 Dutch-language websites via Google and Ixquick and investigated the correlation between the quality of the contents measured by 4 parameters and the presence of incorrect information, site characteristics, the DISCERN score and Google PageRank. RESULTS: The quality of the information was generally poor. The only investigated site characteristic that was found to be associated with basic criteria relating to symptoms and diagnosis was the size of the site. The DISCERN score was significantly correlated with the quality of the information. The occurrence of incorrect information was independent of the quality of the content, site characteristics, Google PageRank and DISCERN scores. CONCLUSION: The quality of Dutch-language websites on the subject of OCD is inadequate. Site characteristics and Google PageRank are not good predictors of the quality of information. The DISCERN rating tool is a potentially valuable indicator of content quality with regard to treatment options.

Evidence-Based Medicine↗
PubMed2005

Increased expression of high mobility group box 1 (HMGB1) is associated with an elevated level of the antiapoptotic c-IAP2 protein in human colon carcinomas.

BACKGROUND: High mobility group box 1 (HMGB1) is a non-histone chromosomal protein implicated in a variety of biologically important processes, including transcription, DNA repair, V(D)J recombination, differentiation, and development. Overexpression of HMGB1 inhibits apoptosis, arguing that the molecule may act as an antiapoptotic oncoprotein. Indeed, increased expression of HMGB1 has been reported for several different tumour types. In this study, we analysed human colon carcinoma for HMGB1 as well as for c-IAP2 expression levels. c-IAP2 is an antiapoptotic protein which may be upregulated as a consequence of nuclear factor kappaB (NFkappaB) activation via HMGB1. METHODS: A comparative genomic hybridisation (CGH) database comprising 1645 cases from different human tumour types was screened to detect cytogenetic changes at the HMGB1 locus. Immunohistochemical staining of human colon tissue microarrays and tumour biopsies, as well as western blot analysis of tumour lysates, were performed to detect elevated HMGB1 and c-IAP2 expression in colon carcinomas. The antiapoptotic potential of HMGB1 was analysed by measuring caspase activities, and luciferase reporter assays and quantitative polymerase chain reaction analysis were employed to confirm NFkappaB activation and c-IAP2 mRNA upregulation on HMGB1 overexpression. RESULTS: According to CGH analysis, the genomic locus containing the HMGB1 gene was overrepresented in one third (35/96) of colon cancers. Correspondingly, HMGB1 protein levels were significantly elevated in 90% of the 60 colon carcinomas tested compared with corresponding normal tissues evaluable from the same patients. HMGB1 increased NFkappaB activity and led to co-overexpression of the antiapoptotic NFkappaB target gene product c-IAP2 in vitro. Furthermore, increased HMGB1 levels correlated with enhanced amounts of c-IAP2 in colon tumours analysed by us. Finally, we demonstrated that HMGB1 overexpression suppressed caspase-9 and caspase-3 activity, suggesting that HMGB1 interferes with the apoptotic machinery at the level of apoptosomal caspase-9 activation. CONCLUSIONS: We identified in vitro a molecular pathway triggered by HMGB1 to inhibit apoptosis via c-IAP2 induction. Our data indicate a strong correlation between upregulation of the apoptosis repressing HMGB1 and c-IAP2 proteins in the pathogenesis of colon carcinoma.

Apoptosis↗
PubMed2005

Amplification of Cyclin L1 is associated with lymph node metastases in head and neck squamous cell carcinoma (HNSCC).

Overrepresentation of chromosomal bands 3q25-q29 has been associated with shortened disease-specific survival in head and neck squamous cell carcinoma (HNSCC). To assess the prevalence of copy number gains (>4 signals per cell) and high-level amplifications (>8 signals per cell) from putative oncogenes in this chromosomal region (CCNL1, SNO, PIK3CA, TP73L), tissue microarray analysis was applied on 280 HNSCCs by fluorescence in situ hybridization. Overall frequency of additional copy numbers was 34.3% for CCNL1, 31.8% for SNO, 39.0% for PIK3CA and 38.3% for TP73L, respectively. In general, gains were more frequently detected in stage IV compared to stage I-III tumours. Performing multivariate logistic regression analysis, a significant association of CCNL1 gains and the presence of lymph node metastases was found, which was independent of anatomical site and T-stage of the primary tumour (P=0.049). Site-specific subgroup analysis further showed that copy number gains of CCNL1 and SNO occurred more frequently in oral carcinomas in advanced clinical stages as compared to N0 oral lesions (CCNL1: P=0.03; SNO: P=0.03). Finally, Kaplan-Meier analysis revealed that high-level amplifications of CCNL1 correlated with shorter overall survival of the patients. Our results indicate that CCNL1 plays a critical role in the loco-regional progression of HNSCC and may serve as an indicator for occult advanced tumour stages.

Biomarkers, Tumor↗
PubMed2004

Acupuncture and Chinese herbal medicine in the treatment of patients with seasonal allergic rhinitis: a randomized-controlled clinical trial.

BACKGROUND: Patients with allergic rhinitis (AR) increasingly use complementary medicine. The aim of this study was to determine whether traditional Chinese therapy is efficacious in patients suffering from seasonal AR. METHODS: Fifty-two patients between the ages of 20 and 58 who had typical symptoms of seasonal AR were assigned randomly and in a blinded fashion to (i) an active treatment group which received a semi-standardized treatment of acupuncture and Chinese herbal medicine, and (ii) a control group which received acupuncture applied to non-acupuncture points in addition to a non-specific Chinese herbal formula. All patients received acupuncture treatment once per week and the respective Chinese herbal formula as a decoction three times daily for a total of 6 weeks. Assessments were performed before, during, and 1 week after treatment. The change in severity of hay fever symptoms was the primary outcome measured on a visual analogue scale (VAS). RESULTS: Compared with patients in the control group, patients in the active treatment group showed a significant after-treatment improvement on the VAS (P = 0.006) and Rhinitis Quality of Life Questionnaire (P = 0.015). Improvement on the Global Assessment of Change Scale was noted in 85% of active treatment group participants vs 40% in the control group (P = 0.048). No differences between the two groups could be detected with the Allergic Rhinitis Symptom Questionnaire. Both treatments were well-tolerated. CONCLUSIONS: The results of this study suggest that traditional Chinese therapy may be an efficacious and safe treatment option for patients with seasonal AR.

Acupuncture Therapy↗
PubMed2003

[Gastrointestinal stromal tumors. A morphologic and molecular genetic independent tumor entity with new therapeutic perspectives].

Recent morphological and molecular genetic findings have greatly expanded our understanding of gastrointestinal stromal tumors (GISTs). GISTs are now defined by their overexpression of CD117 (KIT), the receptor for the stem cell factor, and can thus be discriminated from smooth muscle tumors. Cytogenetically, GISTs are characterized even in early lesions by frequent entire or partial loss of the chromosomes 14 and 22 and terminal deletions of the chromosomal arm 1p. During tumor progression further chromosomal imbalances accumulate. Following the first report on activating KIT mutations in GISTs, several studies have addressed the role of wild-type and mutant KIT in GISTs and demonstrated activating KIT mutations in the majority of cases. Moreover, KIT tyrosine phosphorylation is even present in KIT mutation-negative GISTs, implicating KIT activation as a central event in the pathogenesis of GISTs. Imatinib (STI571/Glivec) is a selective inhibitor of BCR/ABL, PDGFR and KIT receptor-tyrosine kinases. First therapeutic applications of imatinib in patients with progressive GISTs have yielded promising results. This review focuses on the morphological and molecular findings in GISTs which have opened up a new therapeutic perspective.

Antigens, CD↗
PubMed2003

[A new dimension of DNA analysis: genomic profiling by matrix CGH].

Analysis of genetic alterations in tumor cells represent a first step to understand the molecular mechanism of cancer etiology and development. Due to the progress in genome research, it is feasible to assess the complexity of genomic changes on a large scale. Protocols for gene expression profiling using cDNA arrays have been developed allowing to test the activity of almost all human genes in tumor cells. Another important approach is matrix-CGH which was recently developed to assess gains and losses on the genomic level with high resolution. This method not only allows to narrow down the position of novel oncogenes or tumor suppressor-genes but also contributes to a refinement of tumor classifications. Since matrix-CGH can be performed under highly standardized conditions in a fully automatized way, it is suited for diagnostics in clinical laboratories.

Chromosome Aberrations↗
PubMed2002

[Opportunities and chances for tissue chip microarrays in head and neck surgery. A novel technique for the rapid evaluation of potentially novel biomarkers].

Oral squamous cell carcinomas (OSCC) are malignant tumors with a poor prognosis and low long-term survival rates, even when using modern adjuvant and neoadjuvant therapy forms in addition to surgery. For the clinical estimation of each tumor, it is necessary to define stage-dependent molecular and/or cellular parameters as it is known that OSCC develop along a multistep pathway including the loss of tumor suppressor genes and the amplification of oncogenes which result in changes in protein expression. In order to establish a reliable pattern of molecular and cellular biomarkers, a large number of tumor specimens from different stages of the disease need to be analysed. In this study, biopsies of a collective of 293 OSCC in different stages were screened with the novel technique of tissue chip microarrays by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). FISH-analysis was performed on the oncogene cyclin D1 and IHC-analysis on the proteins cyclin D1, p53, p16, cdk4, bcl2, mdm2 and rb. Tissue chip technology was shown to facilitate rapid screening for molecular and cellular alterations in different stages of OSCC and revealed reliable and reproducible results that may allow the definition of a multistep pathway model for tumor progression in OSCC.

Aged↗
PubMed2002

Topological organization of the MYC/IGK locus in Burkitt's lymphoma cells assessed by nuclear halo preparations.

In Burkitt's lymphoma (BL) cells characteristic chromosomal translocations juxtapose the MYC oncogene to one of the three immunoglobulin (IG) gene loci. This results in deregulation of MYC expression through IG gene enhancer elements. As enhancers and MYC promoters can be as much as several hundred kilobases apart, long-distance effects are to be postulated, which affect chromatin organization. Since transcriptionally active and inactive sequences can be distinguished based on their localization in nuclear halo preparations, we used this technique to assess the topology of wild-type and translocated MYC and IGK genes. Following visualization of these genes by fluorescence in situ hybridization, the signal distribution was determined in nuclear halo structures of human monocytes and the BL-derived cell line LY66. MYC signals derived from the non-translocated chromosome 8 were found equally distributed between the residual nucleus and the surrounding DNA halo. In contrast, the activated MYC and IGK genes on the translocated chromosome in LY66 cells were associated with the residual nucleus in 78 and 88% of cases, respectively. In LY66 cells, attachment to the residual nucleus was restricted to a DNA segment 30 to 50 kb downstream of MYC, while in monocytes it was dispersed over 80 kb around the MYC gene. These findings indicate a specific chromatin organization for the activated MYC locus. Distance measurements between MYC and IGK signals revealed shorter values than expected from their linear distance (325 kb), indicating a back folding of the DNA backbone. Thus, there is strong evidence for a specific topological organization, which is functionally related to the MYC activation status with the specific folding of the DNA strand likely reflecting maintenance of a spatial interaction between IGK enhancer and MYC promoter elements.

Burkitt Lymphoma↗
PubMed2001

Gain of chromosome arm 9p is characteristic of primary mediastinal B-cell lymphoma (MBL): comprehensive molecular cytogenetic analysis and presentation of a novel MBL cell line.

Primary mediastinal B-cell lymphoma (MBL) is an aggressive Non-Hodgkin's Lymphoma, which has been recognized as a distinct disease entity. We performed a comprehensive molecular cytogenetic study analyzing 43 MBLs. By comparative genomic hybridization (CGH), the most common aberrations were gains of chromosome arms 9p and Xq, which were present in 56% and 40% of cases, respectively. Based on the limited resolution of CGH, this technique may underestimate the real incidence of aberrations. Therefore, we also did an interphase cytogenetic study with eight DNA probes mapping to chromosome regions frequently altered in B-cell lymphomas. With this approach, both 9p and Xq gains were found in more than 70% of cases (75% and 87%, respectively). The findings were compared with results obtained in 308 other B-cell lymphomas. Gains in 9p were identified in only six of the 308 cases, and only one of these lymphomas with 9p gains was not primarily extranodal in origin (P < 10-(20) for CGH data and P < 10-(11) for fluorescence in situ hybridization data). We also present a novel MBL cell line, MedB-1, which carries the genetic aberrations characteristic of this entity.

Adolescent↗
PubMed2001

MDM2 gene amplification and lack of p53 point mutations in Hodgkin and Reed-Sternberg cells: results from single-cell polymerase chain reaction and molecular cytogenetic studies.

Hodgkin's disease (HD) is the most common haematological malignancy after chronic lymphocytic leukaemia, but very little is known about its pathogenesis or the genetic events that contribute to the malignant phenotype of the tumour cells. p53 is assumed to play an important role in the pathogenesis of HD, based on the observation that p53 protein is frequently accumulated in Hodgkin and Reed-Sternberg (H & RS) cells. We investigated single H & RS cells from five different HD patients for point mutations at the genomic level using multiplex polymerase chain reaction amplification and subsequent sequencing. No point mutations were detected in 50 single H & RS cells analysed. Hence, accumulation of p53 protein cannot be explained by mutations within the gene. A genome-wide screening for genomic imbalances using comparative genomic hybridization revealed gain on chromosome 12q14, i.e. the mapping position of the MDM2 gene in several HD cases. Therefore, we assessed the copy number of the MDM2 gene using fluorescence in situ hybridization. In four out of six HD cases analysed, the copy number of the MDM2 gene was found to be increased. As gene amplification is frequently associated with protein overexpression, the observed accumulation of p53 in the nuclei of H & RS cells could be as a result of elevated MDM2 protein levels resulting in stabilization of p53 protein.

Adult↗
PubMed2000

Genomic imbalances including amplification of the tyrosine kinase gene JAK2 in CD30+ Hodgkin cells.

Comparative genomic hybridization was applied for a comprehensive screening of frequently occurring net gains and losses of chromosomal subregions in small populations of CD30+ Hodgkin cells and their morphological variants. In 12 Hodgkin's lymphomas, recurrent gains were detected on chromosomal arms 2p, 9p, and 12q (in six, four, and five tumors, respectively) and distinct high-level amplifications were identified on chromosomal bands 4p16, 4q23-q24, and 9p23-p24. In Hodgkin cells with 9p23-p24 amplification, fluorescence in situ hybridization revealed an increased copy number of chromosomal sequences spanning the tyrosine kinase gene JAK2. Several of the imbalances described, in particular a gain in chromosomal arm 9p that includes JAK2 amplification, are similar to the genomic changes detected in primary mediastinal B-cell lymphoma.

Adolescent↗
PubMed2000

Comparative genomic hybridization: uses and limitations.

Comparative genomic hybridization (CGH) has contributed significantly to the current knowledge of genomic alterations in hematologic malignancies. Characteristic patterns of genomic imbalances not only have confirmed recent classification schemes in non-Hodgkin's lymphoma, but they provide a basis for the successful identification of genes with previously unrecognized pathogenic roles in the development of different lymphomas. Based on its technical limitations, there is little reason to apply CGH to chromosomes of metaphase cells in routine diagnostic settings. However, the new approach of CGH to DNA microarrays, a procedure termed matrix-CGH, overcomes most of the limitations and opens new approaches for diagnostics and identification of genetically defined leukemia and lymphoma subgroups. Current efforts to develop leukemia specific matrix-CGH DNA chips, which are designed to meet the clinical needs, are presented and discussed.

Hematologic Neoplasms↗
PubMed2000

Immunomodulatory effects of acupuncture in the treatment of allergic asthma: a randomized controlled study.

OBJECTIVE: According to Traditional Chinese Medicine (TCM) acupuncture is a suitable treatment for complex chronic diseases such as bronchial asthma. In a randomized, controlled study we investigated immunologic effects of Chinese acupuncture on patients with allergic asthma. PATIENTS AND METHODS: The effects of acupuncture treatment given according to the principles of TCM (TCM group, n = 20) were compared with those of acupuncture treatment using points not specific for asthma (control group, n = 18). All patients were treated 12 times for 30 minutes over a time period of 4 weeks. Patients' general well-being and several peripheral blood parameters (eosinophils, lymphocyte subpopulations, cytokines, in vitro lymphocyte proliferation) were determined before and after acupuncture treatment. RESULTS: In the TCM group, significantly more patients indicated an improvement in general well-being (79% in the TCM group versus 47% in the control group; p = 0.049) after acupuncture treatment. The following changes were found in the TCM group: within the lymphocyte subpopulations the CD3+ cells (p = 0.005) and CD4+ cells (p = 0.014) increased significantly. There were also significant changes in cytokine concentrations: interleukin (IL)-6 (p = 0.026) and IL-10 (p = 0.001) decreased whereas IL-8 (p = 0.050) rose significantly. Additionally, the in vitro lymphocyte proliferation rate increased significantly (p = 0.035) while the number of eosinophils decreased from 4.4% to 3.3% after acupuncture (p > 0.05). The control group, however, showed no significant changes apart from an increase in the CD4+ cells (p = 0.012). CONCLUSION: The results imply that asthma patients benefit from acupuncture treatment given in addition to conventional therapy. Furthermore, acupuncture performed in accordance with the principles of TCM showed significant immune-modulating effects.

Acupuncture Therapy↗
PubMed2000

Detection of chromosomal imbalances in leiomyosarcoma by comparative genomic hybridization and interphase cytogenetics.

Leiomyosarcomas comprise a group of malignant soft-tissue tumors with smooth-muscle differentiation. In this study, 14 cases of leiomyosarcoma were screened for changes in relative chromosome copy number by comparative genomic hybridization. A high number of imbalances (mean, 16.3; range, 6-26) was detected, with chromosomal gains occurring about twice as much as losses. The most frequent gains were found in 5p15, 8q24, 15q25-->q26, 17p, and Xp (43% to 50%), whereas the most frequent losses were found in 10q and 13q (50% and 78%, respectively). Twenty high-level amplifications affecting 15 different chromosomal subregions were detected in nine different tumors. In three leiomyosarcomas, sequences on chromosome arm 17p were found to be highly amplified, with a minimal overlapping region on subbands 17p12-->p11. We further discovered that the Smith-Magenis syndrome critical region on 17p11.2 is included in the 17p amplicons of two leiomyosarcoma cases. Using probes flanking this genetically unstable region, a mean of 14 and 22 signals per nucleus, respectively, was detected in both leiomyosarcomas by fluorescence in situ hybridization. In conclusion, this analysis identifies a number of characteristic chromosomal imbalances in leiomyosarcomas and provides evidence for the localization of potential oncogenes and tumor suppressor genes active in leiomyosarcoma genomes.

Adult↗
PubMed1999

Mapping of the breakpoints on the short arm of chromosome 17 in neoplasms with an i(17q).

Isochromosomes are monocentric or dicentric chromosomes with homologous arms that are attached in a reverse configuration as mirror images. With an incidence of 3-4%, the i(17q) represents the most frequent isochromosome in human cancer. It is found in a variety of tumors, particularly in blast crisis of chronic myeloid leukemia (CML-BC), acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL), and medulloblastoma (MB), and indicates a poor prognosis. To determine the breakpoints on the molecular genetic level, we analyzed 18 neoplasms (six CML, four AML, one NHL, and seven MB) with an i(17q) and two MB with a pure del(17p) applying fluorescence in situ hybridization (FISH) with yeast artificial chromosome (YAC) clones, P1-artificial chromosome (PAC) clones, and cosmids from a well-characterized contig covering more than 6 Mb of genomic DNA. We identified four different breakpoint cluster regions. One is located close to or within the centromere of chromosome 17 and a second in the Charcot-Marie-Tooth (CMT1A) region at 17(p11.2). A third breakpoint was found telomeric to the CMT1A region. The fourth, most common breakpoint was detected in MB, AML, and in CML-BC specimens and was bordered by two adjacent cosmid clones (clones D14149 and M0140) within the Smith-Magenis syndrome (SMS) region. These results indicate that the low copy number repeat gene clusters which are present in the CMT and SMS regions may be one of the factors for the increased instability that may trigger the formation of an i(17q).

Adolescent↗