CD105 (endoglin), a receptor for transforming growth factor beta (TGFbeta), is highly expressed in tissue-cultured, activated endothelial cells vitro and tissues undergoing angiogenesis vivo. The absence of knockout mice leads to their death from defective vascular development, but the role modulation has not been elucidated. TGFbeta1 well-recognized regulator angiogenesis. Using an antisense approach, we have shown that inhibition protein translation cultured human enhances ability suppress...

In contrast to the developed nations, invasive cervical cancer (ICC) is most common womens malignancy in Kenya and many other locations sub-Saharan Africa. However, studies on survival from this disease area of world are severely restricted by lack patient follow-up. We now report a prospective cohort study ICC Kenyan women analysing factors affecting tumour response overall patients undergoing radiotherapy.

Masataka Sugimoto, Takeshi Nakamura, Naoko Ohtani, Lynne Hampson, Ian N. Akira Shimamoto, Yasuhiro Furuichi, Ko Okumura, Shinichiro Niwa, Yoichi Taya, and Eiji Hara Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, M20 4BX, UK; Juntendo University School of Medicine, Tokyo, Japan; Sumitomo Electric Industries, Yokohama, St. Mary's Hospital, Agene Research Institute, Kamakura, Center Japan

After i.p. infection of mice with the intracellular bacterium Mycobacterium bovis bacillus Calmette-Guérin, macrophages recovered from peritoneal cavity display classical signs immune activation. We have identified a member serine protease inhibitor (serpin) family which is highly induced in during Calmette-Guérin infection. Serpin 2a (spi2a) expression also vivo Salmonella typhimurium and Listeria monocytogenes, vitro by variety bacteria bacterial products. The cytokine IFN-gamma induces...

Background Cervical cancer is the most common female malignancy in developing nations and third women globally. An effective, inexpensive self-applied topical treatment would be an ideal solution for of screen-detected, pre-invasive cervical disease low resource settings. Methods Between 01/03/2013 01/08/2013, attending Kenyatta National Hospital's Family Planning Gynaecology Outpatients clinics were tested HIV, HPV (Cervista®) liquid based cytology (LBC -ThinPrep®). HIV negative diagnosed...

Abstract The β-endoglucuronidase heparanase plays an important role in tumor invasion, a process that is significantly enhanced by hypoxia. We have used strategy of stable transfection with antisense to derive ovarian carcinoma cell lines express different levels and these demonstrate invasion correlates activity. Secreted activity was increased reduction, hypoxia, growth cells under reduced oxygen (1%) augmented both which are inhibited treatment antiheparanase antibodies. This the first...

Although HIV protease inhibitor (PI) drugs predominantly target proteases 1 and 2, it is also known that part of their efficacy due to selective inhibition the proteasome. The pathogenicity high-risk human papilloma virus (HPV) dependent on expression viral E6 proteins which inappropriately activate 26S proteasome degrade p53 other cellular are detrimental replication. Comparison ability PIs indinavir, ritonavir, amprenavir, lopinavir, atazanavir, nelfinavir saquinavir inhibit E6-mediated...

SPECIFIC AIMSWe have devised an in vivo experimental model to investigate the role of human papilloma virus (HPV) type 16 E6 and E7 oncoproteins development radiation resistance advanced cervical carcinoma. HPV negative C33A carcinoma cells were transfected with cDNAs transfectants subcutaneously (s.c.) transplanted into scid mice. Tumor growth under normal hypoxic conditions assessed male female recipients. Patterns gene expression investigated radiation-resistant vs. radiation-sensitive...

Guanidine exchange factor (GEF)-catalysed activation of Rho proteins such as Cdc42 has been shown to have a crucial role in cellular transformation, malignant progression and invasion. We previously that the HPV16 E6 oncoprotein binds PDZ domain protein Tax-interacting-protein 1 (Tip-1) we now report identification functional analysis novel Tip-1 binding GEF. Yeast two-hybrid, vitro pull-down, site-directed mutagenesis, semiquantitative PCR, co-immunoprecipitation western blotting were used...

Recently, it has been reported that the anti-viral drug, lopinavir, which is currently used as a human immunodeficiency virus (HIV) protease inhibitor, could also inhibit E6-mediated proteasomal degradation of mutant p53 in E6-transfected C33A cells. In this study, parent control cells and HPV16 were exposed to lopinavir at concentrations ranging from 0 30 µM. The phenotypic response was assessed by Fourier transform infrared (FT-IR) spectroscopy directly on (the metabolic fingerprint) cell...

Previous work has indicated that the PDZ domain Tax interacting protein 1 (Tip-1) is a target of HTLV1 and potential RhoA effector. We have used yeast two-hybrid system to show Tip-1 also interacts with HPV16 E6 protein. This interaction was confirmed by co-immunoprecipitation from expressing C33A cervical carcinoma cells (C33A-E6) which showed not degraded oncoprotein. During routine passage we observed C33A-E6 had less compact morphology were adherent than control vector transfected C33A-V...

Background We have previously shown that the HIV protease inhibitor lopinavir has selective toxicity against human papillomavirus (HPV)-positive cervical carcinoma cells via an unknown mechanism. Methods SiHa were stably transfected with proteasome sensor vector pZsPro-Sensor-1 to confirm inhibits in these cells. The Panorama Xpress profiler 725 antibody array was then used analyse specific changes protein expression lopinavir-treated versus control untreated followed by PCR and western...

Background Cidofovir is currently being used off-licence to treat different viral infections, such as benign low-risk human papillomavirus (HPV)-related recurrent respiratory papillomatosis (RRP). There are concerns over the safety of this practice rat studies demonstrated a high malignant transformation rate. As yet, there no clinical reports cidofovir-induced changes in humans. Methods Telomerase immortalised keratinocytes (hTert) stably expressing E6 proteins from either HPV6b or...

Purpose: To examine the effect of human papillomavirus (HPV) type 16-E6 (HPV 'early' gene) oncoprotein on in vitro radiosensitivity HPV-negative/p53 mutant C33a cervical cancer cells.Methods and materials: The cell line was stably transfected with either HPV16 E6 cDNA cloned into vector pcDNA™3.0 (C33aE6) or empty-vector control (C33aV). Radiosensitivity, DNA damage, cycle measurements were made using standard clonogenic assays, immunofluorescent assessment nuclear histone H2AX...

Abstract Background. Cidofovir is a nucleoside analogue that used off‐license to treat recurrent respiratory papillomatosis (RRP) caused by HPV6/11. However, the effect of this drug upon low‐risk HPV 6/11 gene expression unknown. Methods. The E6 was evaluated RT‐PCR in HPV−ve C33A cervical carcinoma cells stably transfected with both low‐ and high‐risk cDNA's SiHa (HPV16+ve) after treatment 2 doses durations exposure cidofovir. Results. Compared vector only transcript, RNA levels showed an...

Although subclinical persistent infections with the human polyomaviruses BKV and JCV are ubiquitous worldwide, these known to vary in relation diseases present geographical location. DNAs from 220 cervical smears 109 invasive carcinomas obtained HIV positive negative Kenyan women of HPV status were analyzed by nested endpoint PCR for JCV. BKV-JCV DNA was detected 5/105 (4.7%) 6/37 (16%) infected whereas 9/115 (7.8%) 4/72 (5.5%) women. Nested showed that all 24 samples not BKV. more prevalent...

Abstract We investigate the accumulated microbial and autoantigen antibody repertoire in adult-onset dermatomyositis patients sero-positive for TIF1γ (TRIM33) autoantibodies. use an untargeted high-throughput approach which combines immunoglobulin disease-specific epitope-enrichment identification of human antigens. observe antibodies recognizing a wider antigens dermatomyositis. Antibodies viruses Poxviridae family species are significantly enriched. The identified autoantibodies recognise...