Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial.

Background: Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20-30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3.

Chemotherapy for metastatic and recurrent cervical cancer.

Background: Cervical cancer is the second most common cancer among women up to 65 years of age and is the most frequent cause of death from gynaecological cancers worldwide. A woman's risk of developing cervical cancer by 65 years of age ranges from 0.69% in developed countries to 1.

Small cell lung cancer treated in southeast Wales.

Aims: In small cell lung cancer (SCLC), consolidation thoracic irradiation (CTI) increases 3-year absolute survival by 5.4% in patients with limited disease and a complete response to chemotherapy. Early concurrent thoracic radiotherapy has been shown to improve local control and prolong survival compared with CTI in some trials.

Initial oxygen management in patients with an exacerbation of chronic obstructive pulmonary disease.

Background: The Norfolk and Norwich University Hospital (NNUH) is situated in rural Norfolk, and ambulance journey times are often >30 min. Longer ambulance journeys could lead to a greater risk of hypercapnia, if inappropriately high concentrations of oxygen are given during an exacerbation of COPD.

Aim: To investigate the effect of high concentration oxygen (HCO, FiO(2) > 0.

Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells.

Growth factor independence-1 (GFI1) and GFI1B are closely related, yet differentially expressed transcriptional repressors with nearly identical DNA binding domains. GFI1 is upregulated in the earliest thymocyte precursors, while GFI1B expression is restricted to T lymphopoiesis stages coincident with activation. Transgenic expression of GFI1 potentiates T-cell activation, while forced GFI1B expression decreases activation.

Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor.

The Gfi-1 proto-oncogene encodes a zinc finger protein with six C2H2-type, C-terminal zinc finger motifs and is activated by provirus integration in T-cell lymphoma lines selected for interleukin-2 independence in culture and in primary retrovirus-induced thymomas. Gfi-1 expression in adult animals is restricted to the thymus, spleen, and testis and is enhanced in mitogen-stimulated splenocytes. In this report, we show that Gfi-1 is a 55-kDa nuclear protein that binds DNA in a sequence-specific manner.

Replacement of interleukin-2 (IL-2)-generated mitogenic signals by a mink cell focus-forming (MCF) or xenotropic virus-induced IL-9-dependent autocrine loop: implications for MCF virus-induced leukemogenesis.

In earlier studies, we have shown that superinfection of an interleukin-2 (IL-2)-dependent, Moloney murine leukemia virus (MoMuLV)-induced rat T-cell lymphoma line (4437A) with mink cell focus-forming (also called polytropic) murine retroviruses induces rapid progression to IL-2-independent growth. In this report, we present evidence that the vast majority (> 90%) of the IL-2-independent lines established from polytropic or xenotropic virus-infected 4437A cells carry provirus insertions in the 3' untranslated region of the IL-9 receptor gene (Gfi-2 [for growth factor independence-2]/IL-9R). Prior to superinfection, the cells express neither IL-9 nor IL-9R.

Sequence-specific binding of a c-myc nuclear-matrix-associated region shows increased nuclear matrix retention after leukemic cell (HL-60) differentiation.

HL-60 cells, a human promyelocytic leukemia cell line, contain amplified c-myc DNA sequences and mRNA transcripts. These cells can be induced to undergo macrophage differentiation by phorbol esters, which results in suppression of c-myc expression and cessation of cell proliferation. The nuclear matrix (NM), a nuclear skeleton resistant to DNase I digestion and high salt extraction, is proposed to be involved in DNA replication, gene regulation, and the correct distribution of DNA at mitosis.

Identification of a nuclear matrix-associated region of the c-myc protooncogene and its recognition by a nuclear protein in the human leukemia HL-60 cell line.

A nuclear matrix (NM)-associated region (MAR) of the protooncogene c-myc is identified in a human leukemia cell line (HL-60). A binding assay between isolated NM and 32P-end-labeled c-myc fragments in the presence of unlabeled competitors was used, and a 3'-end DraI/DraI fragment of 172 base pairs containing the first of the two polyadenylation [poly(A)] signals was identified as an in vitro MAR. Direct detection of endogenous c-myc fragments remaining NM bound after restriction digestion was used, and an in vivo MAR has been identified as the ClaI/EcoRI 1.

Bleed fastness of fluorescent whitening agents in mass whitened paper.

Paper samples mass whitened with fluorescent whiteing agents (FWAs) of three different types (di-, tetra-, and hexasulfonated derivatives of 4,4'-diaminostilbene-2,2'-disulfonic acid) were examined for bleed fastness in five different eluents. Fluorescece intensity was measured by a sensitive spectrofluorimetric technique instead of the usual visual assessment. The degree of bleed obtained from each of the FWAs tested was less than 0.