Circulating vascular endothelial growth factor (VEGF) levels in advanced stage cancer patients compared to normal controls and diabetes mellitus patients with critical ischemia.

Anti-angiogenic therapy is emerging as a valuable tool in the treatment of patients with cancer. As VEGF is a central target in anti-angiogenic therapy, its levels in the circulation might be relevant in selecting tumor types or patients likely to respond to this treatment. Additional VEGF has been recognized as a key factor in the pathogenesis of diabetic retinopathy.

Prognostic significance of tumor necrosis factor-related apoptosis-inducing ligand and its receptors in adjuvantly treated stage III colon cancer patients.

Purpose: In preclinical models, there is synergism between chemotherapy and recombinant human tumor necrosis factor (TNF) -related apoptosis-inducing ligand (TRAIL) on apoptosis induction in tumor cells. Therefore, the prognostic relevance was analyzed of the expression of TRAIL and its death receptors DR4 and DR5 on disease-free survival and overall survival in stage III colon cancer patients treated with adjuvant chemotherapy.

Methods: Tissue microarrays were constructed of primary tumor tissue from 376 stage III colon cancer patients treated in a randomized adjuvant chemotherapy study (fluorouracil/levamisole v fluorouracil/levamisole/leucovorin) and stained immunohistochemically for TRAIL, DR4, and DR5.

[InterPro as a new tool for whole genome analysis. A comparative analysis of Mycobacterium tuberculosis, Bacillus subtilis and Escherichia coli as a case study].

InterPro was developed as a new integrated documentation resource for protein families, domains and functional sites to rationalize the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects and has applications in computational functional classification of newly determined sequences lacking biochemical characterization and in comparative genome analysis. InterPro contains over 3500 entries, with more than 1000000 hits in SWISS-PROT and TrEMBL. The database is accessible for text- and sequence-based searches at http://www.

Outcome of palliative care regimens in patients with advanced oesophageal cancer detected during explorative surgery.

Background: The outcome of different palliative regimens was investigated in patients with incurable oesophageal carcinoma identified during surgical exploration.

Patients And Methods: Between January 1992 and December 2002, 203 patients with oesophageal cancer underwent surgery after a standard staging procedure including computer tomography and endoscopic ultrasonography. The data from 78 patients, rendered incurable at exploration and who subsequently underwent palliative interventions, were analysed retrospectively.

Treatment with intramuscular vascular endothelial growth factor gene compared with placebo for patients with diabetes mellitus and critical limb ischemia: a double-blind randomized trial.

Despite advances in revascularization techniques, limb salvage and relief of pain cannot be achieved in many diabetic patients with diffuse peripheral vascular disease. Our objective was to determine the effect of intramuscular administration of phVEGF165 (vascular endothelial growth factor gene-carrying plasmid) on critical limb ischemia (CLI) compared with placebo (0.9% NaCl).

Systemic VEGF levels after coronary artery bypass graft surgery reflects the extent of inflammatory response.

Background: Circulating vascular endothelial growth factor (VEGF) was studied as a substitute endpoint for treatment response after VEGF plasmid therapy. The effect of coronary artery bypass surgery (CABG) with cardiopulmonary bypass (CPB) on systemic VEGF levels are however largely unknown, therefore, we studied the effect of this procedure to measure VEGF levels after surgery alone.

Methods: Fourteen patients requiring CABG were included.

Randomised Phase III study of biweekly 24-h infusion of high-dose 5FU with folinic acid and oxaliplatin versus monthly plus 5-FU/folinic acid in first-line treatment of advanced colorectal cancer.

Background: A phase III study was started to compare oxaliplatin/5FU/LV in the first-line with bolus FU/LV in metastatic colorectal cancer.

Patients And Methods: 302 patients were randomised and received bolus 5-FU 425 mg/m(2) day 1-5, FA 20 mg/m(2) day 1-5, q 4 wk or oxaliplatin 85 mg/m(2), 2 h-infusion, FA 200 mg/m(2), 1-h infusion. 5-FU 2600 mg/m(2), 24-h infusion day 1, q 2 wk.

18F-FEAU as a radiotracer for herpes simplex virus thymidine kinase gene expression: in-vitro comparison with other PET tracers.

Objective: The herpes simplex virus thymidine kinase (HSVtk) gene has frequently been applied as a reporter gene for monitoring transgene expression in animal models. In clinical gene therapy protocols, however, extremely low expression levels of the transferred gene are generally observed. Consequently, sensitive and selective radiotracers for imaging are required.

A review on pro- and anti-angiogenic factors as targets of clinical intervention.

Angiogenesis plays an important role in physiology and pathology. It is a tightly regulated process, influenced by the microenvironment and modulated by a multitude of pro- and anti-angiogenic factors. A thorough understanding of the angiogenic process may lead to novel therapies to target ischemic vascular diseases as well as diseases characterised by excessive angiogenesis such as rheumatoid arthritis, psoriasis or tumours.

Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study.

Purpose: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

Patients And Methods: Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score < or = 46 defined as fatigue), poor mental health using mental health scale (score < or = 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy.

The transcriptional landscape of the mammalian genome.

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins.

Determination of TP53 mutation is more relevant than microsatellite instability status for the prediction of disease-free survival in adjuvant-treated stage III colon cancer patients.

Purpose: Microsatellite instability (MSI), TP53 mutation, and KRAS mutation status have been reported as prognostic factors in colon cancer. Most studies, however, have included heterogeneous groups of patients with respect to cancer stage. We determined the prognostic relevance of high-frequency MSI (MSI-H), TP53 mutations, and KRAS mutations in a well-defined group of patients with stage III colon cancer (N = 391), randomly assigned for adjuvant treatment with fluorouracil-based chemotherapy.

Influence of p53 status on the HSV-Tk/GCV-induced bystander effect in a panel of human ovarian carcinoma cell lines.

The p53 protein is mutated in 50% of all human tumors and plays a key role in apoptosis, cell cycle, and the expression of several genes. We investigated if p53 mutations influence the herpes simplex virus thymidine kinase (HSV-tk)/ganciclovir (GCV)-induced bystander effect (BE). Additionally, we studied some of the underlying mechanisms.

Antagonism of HSV-tk transfection and ganciclovir treatment on chemotherapeutic drug sensitivity.

Our study focused on the influence of herpes simplex virus thymidine kinase (HSV-tk) expression and ganciclovir (GCV) treatment on the sensitivity of C6 glioma cells to frequently used chemotherapeutic drugs, i.e. adriamycin (ADR), cisplatin (CDDP), 5-fluorouracil (5-FU), and methotrexate (MTX).

[New oncolytic agents and immunomodulators and their application].

After a long period without change, colorectal oncology has in recent years entered the frontline of progress in cancer treatment and research. Improved diagnostic techniques have brought forward the diagnosis of metastatic disease, enabling potential curative surgery in the case of liver metastases. Due to both the earlier start of systemic treatment and the increase in number of active drugs, survival of patients with metastatic disease has increased to a median of approximately 18 months.

InterProScan: protein domains identifier.

InterProScan [E. M. Zdobnov and R.

Relevance of high-dose chemotherapy in solid tumours.

Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates.

[18F]FHPG positron emission tomography for detection of herpes simplex virus (HSV) in experimental HSV encephalitis.

Herpes simplex virus type 1 (HSV-1) is one of the most common causes of sporadic encephalitis. The initial clinical course of HSV encephalitis (HSE) is highly variable, and the infection may be rapidly fatal. For effective treatment with antiviral medication, an early diagnosis of HSE is crucial.

Closed system generation of dendritic cells from a single blood volume for clinical application in immunotherapy.

Dendritic cells (DC) used for clinical trials should be processed on a large scale conforming to current good manufacturing practice (cGMP) guidelines. The aim of this study was to develop a protocol for clinical grade generation of immature DC in a closed-system. Aphereses were performed with the Cobe Spectra continuous flow cell separator and material was derived from one volume of blood processed.

Addition of oxaliplatin to neo-adjuvant radiochemotherapy for irresectable rectal cancer, a phase I study.

Background: The aim was to determine the maximum tolerable dose of oxaliplatin added to (oral) 5FU in irresectable rectal cancer.

Patients And Methods: Nineteen patients were treated; 13 patients received 5FU/LV and 6 patients capecitabine. Oxaliplatin was administered on days 1 and 29 at dose levels 85 and 130 mg/m2.

Consequences of chemoresistance for the herpes simplex virus thymidine kinase/ganciclovir-induced bystander effect in a human small cell lung cancer cell line model.

This paper focuses on the influence of chemoresistance on the herpes simplex virus (HSV-tk)/ganciclovir (GCV)-induced bystander effect (BE), as studied in a human small cell lung cancer (SCLC) cell line (GLC4) and its sublines with in vitro acquired resistance to adriamycin (GLC4/ADR), mitoxantrone (GLC4/MITO) and cisplatin (GLC4/CDDP). Chemoresistance for adriamycin, mitoxantrone and cisplatin significantly changed GCV sensitivity. A significant BE was found in all GLC4 cell lines.

Circulating vascular endothelial growth factor during the normal menstrual cycle.

Background: The purpose of the study was to investigate whether cycle-related variations in circulating Vascular Endothelial Growth Factor (VEGF) levels would increase the metastatic potential at specific times during the menstrual cycle.

Materials And Methods: VEGF levels in serum and whole blood were evaluated during the normal menstrual cycle in premenopausal women. Determination of the menstrual phase was based on hormonal measurements.

InterPro, progress and status in 2005.

InterPro, an integrated documentation resource of protein families, domains and functional sites, was created to integrate the major protein signature databases. Currently, it includes PROSITE, Pfam, PRINTS, ProDom, SMART, TIGRFAMs, PIRSF and SUPERFAMILY. Signatures are manually integrated into InterPro entries that are curated to provide biological and functional information.

Developments in treatment of primary irresectable rectal cancer.

Abstract The treatment options for primary irresectable rectal cancers are discussed. Assessment of tumour stage is the first step for an appropriate choice of treatment. Following a diagnosis of rectal cancer, a vast array of diagnostic procedures is available to determine its stage, and thereby its best treatment options.