Direct identification of differentially expressed genes by cycle sequencing and cycle labelling using the differential display PCR primers

Differential display PCR (DD-PCR) is an mRNA fingerprinting technique to identify differentially expressed genes by comparative display of arbitrarily amplified cDNA subsets. This attractively simple screening method was, however, followed by a labour intensive multistep identification procedure for DD-PCR products. In this report we demonstrate for the mouse mast cell protease 2 (MMCP-2) and the cytotoxic T-lymphocyte associated gene transcript CTLA-1 a streamlined approach by (i) direct cycle sequencing with the upstream differential display (DD) primer, followed by (ii) the PCR based generation of an antisense northern probe with the downstream anchor prime

Biosensors in Biomedical Research: Development and Applications of Gene Chips

Nucleic-acid hybridisation techniques are a central tool for the genetic analysis of biological systems. Gene chips are complex arrays of recombinant plasmids or oligonucleotides immobilised on a glass chip of only 1 cm2. This technology allows, for the first time, the multiparallel expression-analysis of thousands of genes. Gene chips will be indispensable tools for the upcoming analysis of the human genome, once the entire sequence is known

Role of Versican, Hyaluronan and CD44 in Ovarian Cancer Metastasis

There is increasing evidence to suggest that extracellular matrix (ECM) components play an active role in tumor progression and are an important determinant for the growth and progression of solid tumors. Tumor cells interfere with the normal programming of ECM biosynthesis and can extensively modify the structure and composition of the matrix. In ovarian cancer alterations in the extracellular environment are critical for tumor initiation and progression and intra-peritoneal dissemination. ECM molecules including versican and hyaluronan (HA) which interacts with the HA receptor, CD44, have been shown to play critical roles in ovarian cancer metastasis. This review focuses on versican, HA, and CD44 and their potential as therapeutic targets for ovarian cancer

IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.</p> <p>Methods</p> <p>We used an <it>ex vivo </it>culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. <it>In vitro </it>data were correlated with <it>in vivo </it>findings by comparing the results with published expression datasets on human cancer biopsies.</p> <p>Results</p> <p>Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (<it>P </it>= 0.029 - Norway/Stanford and <it>P </it>= 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (<it>P </it>= 0.007 - Bhattacharjee and <it>P </it>= 0.008 - Garber dataset).</p> <p>Conclusion</p> <p>Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.</p> <p>See the related commentary by Werner and Bruchim: <url>http://www.biomedcentral.com/1741-7015/8/2</url></p

Outcome of Hospitalized Cancer Patients with Hypernatremia: A Retrospective Case-Control Study

Hypernatremia (>145 mmol/L) is a relatively rare event, and the data regarding its role in the outcome of inpatients on an oncology ward are weak. The aim of this study was to describe the prevalence, prognosis, and outcome of hospitalized cancer patients with hypernatremia. We performed a retrospective case-control study of data obtained from inpatients with a solid tumor at the St. Claraspital, Basel, Switzerland, who were admitted between 2017 and 2020. The primary endpoint was overall survival. Hypernatremia was found in 93 (3.16%) of 2945 inpatients bearing cancer or lymphoma. From 991 eligible normonatremic control patients, 93 were matched according to diagnosis, age, and sex. The median overall survival time (OS) of patients with hypernatremia was 1.5 months compared to 11.7 months of the normonatremic controls (HR 2.69, 95% CI 1.85–3.90, p p p p < 0.001). These results suggest hypernatremia to be associated with an unfavorable outcome and a very short OS

Much has changed in the last decade except overall survival: A Swiss single center analysis of treatment and survival in patients with stage IV non-small cell lung cancer.

BACKGROUND:Molecular therapies for cancers with targetable driver mutations and immunotherapies have revolutionized treatment of non-small cell lung cancer (NSCLC) during the last decade. International treatment guidelines began integrating targeted therapies in 2009 and immunotherapies in 2015. The aim of this study was to examine whether the benefits described for these new therapies in pivotal phase III trials have been translated to a real world patient population. PATIENTS AND METHODS:Data from all consecutive patients diagnosed with stage IV NSCLC diagnosed at a community hospital in Switzerland between 2007 and 2018 were analyzed. Three groups of patients were compared, namely patients diagnosed before 2009 (group 1), between 2009 and 2015 (introduction of targeted therapies, group 2) and after 2015 (introduction of immunotherapies, group 3). The primary outcome was overall survival (OS). Time to treatment failure was a secondary outcome. Both endpoints were estimated using the Kaplan Meyer method and compared by log-rank test. RESULTS:408 patients were included. Patient characteristics were similar in the three groups. Median OS in groups 1, 2, and 3 was 9.8 (95% CI, 6.2 to 13.4), 9.9 (95% CI, 7.6 to 12.1) and 8.6 (95% CI, 6.6 to 10.5) months, respectively (p = 0.5). Across groups patients treated with targeted- and immunotherapies had a significantly better outcome than those treated with chemotherapy or best supportive care (p<0.001). Nevertheless, OS remained unchanged between groups despite adequate molecular testing and integration of targeted- and immunotherapies. Over time, the patient population got more morbid with respect to tumor burden (p = 0.02) and co-morbidities (p = 0.02). CONCLUSIONS:While selected subgroups of patients may benefit from new therapies, outcome in this unselected population of patients with stage IV NSCLC treated in daily practice has not improved over the last decade

Global Gene Expression Analysis of the Interaction between Cancer Cells and Osteoblasts to Predict Bone Metastasis in Breast Cancer

Background: Bone metastasis is a main cause of morbidity in breast cancer. Since breast cancer is a heterogeneous disease, the interactions of cancer cells with the skeletal host cells might also be diverse. We hypothesized that gene expression signatures induced by heterotypic interaction of breast cancer cells and osteoblasts might be of clinical relevance. Methodology/Principal Findings: We established an ex vivo co-culture model using benign breast epithelial cells or a panel of 5 malignant breast epithelial cells in combination with primary human osteoblasts and determined associated gene expression changes with HEEBO microarrays. Pretreatment gene expression profiles of 295 early stage breast cancers published from the Netherlands Cancer Institute with a median follow up of 12.6 years allowed evaluating in vitro effects in the in vivo situation.The effects of the interaction between osteoblasts and breast cancer cell lines of different origin were very heterogeneous. Hs578T cells started to proliferate in co-culture with osteoblasts, SKBR-3 induced a TGF-b response and MDA-MB231 cells showed two distinct sets of up-regulated genes: A set of interferon response genes associated with an upregulation of STAT1 was in vivo remarkably coherent providing a basis for segregation of tumors into two groups. In a univariate analysis, early stage tumors with high expression levels (n = 136) of this gene set had a significantly lower overall survival rate (p = 0.005) (63 % at 10 years) than tumors with low expression levels (n = 159) (overall survival: 77 % at 10 years). The second gene set was associated with IL-6 and did not significantly change the overall survival rate (p = 0.165), but wa