Comparison of sexual function between sacrocolpopexy and sacrocervicopexy.

Objective: To compare sexual function before and 12 months after between sacrocolpopexy and sacrocervicopexy.

Methods: This retrospective study examined a cohort of 55 sexually active women who underwent either supracervical hysterectomy with sacrocervicopexy (n=28) or total abdominal hysterectomy with sacrocolpopexy (n=27) for stage II to IV pelvic organ prolapse. Pelvic floor support was measured with Pelvic Organ Prolapse-Quantification examination.

Polymorphisms in circadian genes, night work and breast cancer: results from the GENICA study.

Objectives: The role of genetic variants and environmental factors in breast cancer etiology has been intensively studied in the last decades. Gene-environment interactions are now increasingly being investigated to gain more insights into the development of breast cancer, specific subtypes, and therapeutics. Recently, night shift work that involves circadian disruption has gained rising interest as a potential non-genetic breast cancer risk factor.

Night work and breast cancer estrogen receptor status--results from the German GENICA study.

Objectives: The potential mechanisms that link night-shift work with breast cancer have been extensively discussed. Exposure to light at night (LAN) depletes melatonin that has oncostatic and anti-estrogenic properties and may lead to a modified expression of estrogen receptor (ER) α. Here, we explored the association between shift work and breast cancer in subgroups of patients with ER-positive and -negative tumors.

Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO-PK0104).

Objective: AIO-PK0104 investigated two treatment strategies in advanced pancreatic cancer (PC): a reference sequence of gemcitabine/erlotinib followed by 2nd-line capecitabine was compared with a reverse experimental sequence of capecitabine/erlotinib followed by gemcitabine.

Methods: 281 patients with PC were randomly assigned to 1st-line treatment with either gemcitabine plus erlotinib or capecitabine plus erlotinib. In case of treatment failure (eg, disease progression or toxicity), patients were allocated to 2nd-line treatment with the comparator cytostatic drug without erlotinib.

Early prediction of nonprogression in advanced non-small-cell lung cancer treated with erlotinib by using [(18)F]fluorodeoxyglucose and [(18)F]fluorothymidine positron emission tomography.

Purpose: Positron emission tomography (PET) with both 2'-deoxy-2'-[(18)F]fluoro-D-glucose (FDG) and 3'-[(18)F]fluoro-3'-deoxy-L-thymidine (FLT) was evaluated with respect to the accuracy of early prediction of nonprogression following erlotinib therapy, independent from epidermal growth factor receptor (EGFR) mutational status, in patients with previously untreated advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Thirty-four patients with untreated stage IV NSCLC were evaluated in this phase II trial. Changes in FDG and FLT uptake after 1 (early) and 6 (late) weeks of erlotinib treatment were compared with nonprogression measured by computed tomography after 6 weeks of treatment, progression-free survival (PFS), and overall survival (OS).

Enhancing adherence to capecitabine chemotherapy by means of multidisciplinary pharmaceutical care.

Purpose: In this prospective multi-centre observational cohort study, we investigated the effect of an intensified multidisciplinary pharmaceutical care programme on the adherence of cancer patients treated with capecitabine, a prodrug of fluorouracil.

Patients And Methods: Twenty-four colorectal and 24 breast cancer patients participated in this study. Patients of the control group (n = 24) received standard care, patients of the intervention group (n = 24) received intensified pharmaceutical care consisting of written and spoken information.

Night work and breast cancer - results from the German GENICA study.

Objectives: Some epidemiological and animal data indicate that night work might increase the risk for breast cancer. We have investigated the risk in a German population-based case-control study known as GENICA (gene environment interaction and breast cancer).

Methods: The GENICA study involved interviews to assess shift work information in 857 breast cancer cases and 892 controls.

Association of ESR1 gene tagging SNPs with breast cancer risk.

We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55,000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations.

Breast cancer risk reduction and membrane-bound catechol O-methyltransferase genetic polymorphisms.

Catechol O-methyltransferase (COMT)-catalyzed methylation of catecholestrogens has been proposed to play a protective role in estrogen-induced genotoxic carcinogenesis. We have taken a comprehensive approach to test the hypothesis that genetic variation in COMT might influence breast cancer risk. Fifteen COMT single nucleotide polymorphisms (SNPs) selected on the basis of in-depth resequencing of the COMT gene were genotyped in 1,482 DNA samples from a Mayo Clinic breast cancer case control study.

Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera.

We report that TG101348, a selective small-molecule inhibitor of JAK2 with an in vitro IC50 of approximately 3 nM, shows therapeutic efficacy in a murine model of myeloproliferative disease induced by the JAK2V617F mutation. In treated animals, there was a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis, and, at least in some instances, evidence for attenuation of myelofibrosis. There were no apparent toxicities and no effect on T cell number.

Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men.

Objective: The combination of simvastatin, an HMG-CoA reductase inhibitor, and ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesterol synthesis and absorption and reduces circulating LDL-cholesterol concentrations. The molecular mechanisms underlying the pronounced lipid-lowering effects of this combination have not been fully elucidated in humans.

Methods And Results: One center, prospective, randomized, parallel three-group study in 72 healthy men (mean age 32+/-9 years, mean body mass index 25.

Tryptase detection in bone-marrow blood: a new diagnostic tool in systemic mastocytosis.

Background: The condition mastocytosis includes a heterogenous group of disorders that are characterized by abnormal growth and accumulation of mast cells. The detection of serum tryptase, an essential mast cell enzyme, is a widely used tool in the diagnosis of mastocytosis. The diagnosis of systemic mastocytosis is substantially based on the histologic examination of bone-marrow biopsy specimens.

Identification of differentially expressed genes involved in the formation of multicellular tumor spheroids by HT-29 colon carcinoma cells.

The multicellular tumor spheroid (MCTS) model represents a suitable in vitro model recreating in vivo tumor formation. The aim of this study was to identify differentially expressed genes that could potentially serve as predictive gene markers for MCTS and be involved in the formation of MCTS. Using the suppression subtractive hybridization (SSH) method, we identified ERBB2/HER2-interacting protein (Erbin), Tumor rejection gp96 (Tr-gp96), 12S ribosomal RNA (12S rRNA), ATP synthase, Kruppel-like transcription factor 5 (KLF5), transcription factor-like 5 (TCFL5), and the dual-specificity phosphatase 11 (DUSP11) to be overexpressed in 3-day-old HT-29 colon carcinoma MCTSs compared to HT-29 colon carcinoma cells grown in monolayer.

Randomized trial of single compared with tandem high-dose chemotherapy followed by autologous stem-cell transplantation in patients with chemotherapy-sensitive metastatic breast cancer.

Purpose: To compare progression-free survival between single and tandem high-dose chemotherapy (HDT) followed by autologous stem-cell transplantation in chemotherapy-sensitive metastatic breast cancer patients.

Patients And Methods: Between February 1997 and June 2001, 187 patients with complete and partial remission were randomly assigned to receive either one or two cycles of HDT, consisting of thiotepa (125 mg/m2/d for 4 days), cyclophosphamide (1,500 mg/m2/d for 4 days), and carboplatin (200 mg/m2/d for 4 days), followed by autologous stem-cell transplantation.

Results: One hundred seventy one of 187 randomly assigned patients completed first HDT, but only 52 of 85 completed the second HDT cycle in the tandem HDT arm.

Expression of xenobiotic and steroid hormone metabolizing enzymes in human breast carcinomas.

The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore, the authors investigated the protein expression of Glutathione S-transferase (GST) isoforms and cytochrome P450 (CYP) known to be involved in the metabolism of steroid hormones and endogenous as well as exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression. Expression of GST pi, mu, alpha and CYP1A1/2, 1A2, 3A4/5, 1B1, 2E1 was assessed by immunohistochemistry for primary breast carcinomas of 393 patients from the German GENICA breast cancer collection.

Loss of imprinting of the insulin-like growth factor 2 and the H19 gene in testicular seminomas detected by real-time PCR approach.

IGF2 and H19 are imprinted genes in normal human tissue, but many studies have observed a loss of imprinting (LOI) of these genes in tumors as an epigenetic alteration of the DNA, that leads to a biallelic expression predisposing cells to carcinogenesis and tumor growth. The aim of this study was to test the reliability of LightCycler-assisted Real-time PCR in detecting LOI of IGF2 and H19 in 39 patients with testicular germ cell tumors by comparing these results with the analysis generated by the golden standard restriction fragment length polymorphism (RFLP). With LightCycler-assisted Real-time PCR for IGF2 44% and for H19 49% of the patients were found to be heterozygous.

Role of exposure to radon and silicosis on the cell type of lung carcinoma in German uranium miners.

Background: In East Germany, uranium mining was undertaken on a large scale from 1946 to 1990. Poor working conditions led to a high level of exposure to ionizing radiation and quartz dust. This analysis evaluates the histopathology of lung carcinoma in uranium miners in relation to radon exposure and silicosis.

Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial.

Background: Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial.

German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer.

CHEK2*1100delC is associated with a twofold increased breast cancer risk. This was shown in a collaborative analysis of European populations, but not in other populations from Europe and the US. Accordingly, there is a need to clarify the role of CHEK2*1100delC in breast cancer.

Gemcitabine and paclitaxel in metastatic or recurrent squamous cell carcinoma of the head and neck: a phase I-II study.

The purpose of this study was to determine the maximum tolerated dose, toxicity profile and anti-tumor activity of paclitaxel in combination with gemcitabine when administered to patients with unresectable locally recurrent or metastatic squamous cell carcinoma of the head and the neck (SCCHN). Twenty-seven patients were treated in a phase I-II study with gemcitabine at a dose of 800 mg/m on days 1 and 8, escalating to a dose of 1,000 mg/m, plus escalating doses of paclitaxel (100, 135 and 175 mg/m) on day 2. Treatment consisted of 6 cycles repeated every 3 weeks.

Cellular retinoic acid-binding protein 2 is down-regulated in prostate cancer.

Prostate cancer is among the most frequent tumours in industrialized nations and many questions remain open concerning the molecular events underlying its development and progression. In the present study we have combined cDNA array hybridization to laser-assisted microdissection (LAM) in order to investigate differences in gene expression between epithelial and stromal cells of prostate cancer and normal peripheral prostate tissue. Results have been verified for selected candidate genes by quantitative real-time RT-PCR.

Factors modifying the association between hormone-replacement therapy and breast cancer risk.

Objectives: Hormone-replacement therapy (HRT) is an established risk factor for breast cancer. HRT users are different from non-users with respect to socio-economic and other characteristics. There may be women where the HRT-related risk could be modulated by other factors.

Identification of p54(nrb) and the 14-3-3 Protein HS1 as TNF-alpha-inducible genes related to cell cycle control and apoptosis in human arterial endothelial cells.

TNF-alpha plays a pivotal role in inflammation processes which are mainly regulated by endothelial cells. While TNF-alpha induces apoptosis of several cell types like tumor cells, endothelial cells are resistant to TNFa mediated cell death. The cytotoxic effects of TNF-alpha on most cells are only evident if RNA or protein synthesis is inhibited, suggesting that de novo RNA or protein synthesis protect cells from TNF-alpha cytotoxicity, presumably by NF-kappaB mediated induction of protective genes.

Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size.

Stem cells reside in a specialized niche that regulates their abundance and fate. Components of the niche have generally been defined in terms of cells and signaling pathways. We define a role for a matrix glycoprotein, osteopontin (OPN), as a constraining factor on hematopoietic stem cells within the bone marrow microenvironment.