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  • Doctoral CRP on Clinical and Experimental Studies to Improve Radiotherapy Outcome in AIDS Cancer Patients

    Closed for proposals

    Project Type

    Coordinated Research Project

    Project Code

    E33022

    CRP

    1338

    Approved Date

    14 April 2003

    Status

    Closed

    Start Date

    15 June 2003

    Expected End Date

    14 June 2010

    Completed Date

    12 July 2011

    Objectives

    To develop more effective and less toxic radiation therapy for cancer of the Uterine Cervix in HIV/AIDS patients

    Specific objectives

    To develop strategies for sensitising tumour cells to radiation, specifically by down regulating specific viral proteins that are known to be factors associated with resistance to radiotherapy

    To perform laboratory studies including PhD projects, of the radiosensitivity of human fibroblasts and cervix cancer cell lines in culture, with or without the addition of various HIV proteins or protease inhibitors (used to treat HIV infections). This will determine the extent of any cellular radiosensitizing properties of these molecules, and help guide the radiotherapy dosage.

    To undertake clinical studies of radiotherapy for cervix cancer with or without the administration of the chemotherapeutic agent Cisplatin, known to be a radiosensitiser.

    Impact

    The doctoral component of the CRP was completed successfully.
    Regarding the clinical component; during the CRP, and particularly towards the end and following completion, scientific groups planning clinical studies on HIV+ cancer patients in the US, approached us interested in the possible findings of our study, to assist them in the design of new clinical trials. After deciding on possible publications, we will probably share our data with these groups.

    Relevance

    The topic is relevant since the combination of HIV+ and certain types of cancer is still a common clinical problem in target countries.
    The CRP shed light on a widespread problem in sub-Saharan Africa which is the deficient follow-up of treated patients in oncology facilities. This problem affects routinely treated patients but it becomes particularly critical when these centres attempt to participate in a clinical trial. A lesson learned from this CRP is that, in these circumstances, significant funds should be allocated to solve the problem of tracking and following patients treated under clinical research protocols. Some of the participating centres, creatively used Agency funds to solve the follow-up problem, while others did not.
    Additional research is needed to address this obstacle.

    CRP Publications

    Type

    Article submitted to peer review journal

    Year

    2006

    Description

    Sun Y, Huang YC, Xu QZ, Wang HP, Bai B, Sui JL, Zhou PK. HIV-1 Tat depresses DNA-PKcs expression and DNA repair, and sensitizes cells to ionizing radiation. Int J Radiat Oncol Biol Phys. 2006 Jul 1; 65(3):842-50.

    Country/Organization

    PR China/ Beijing Institute of Radiation Medicine

    Type

    PhD Thesis

    Year

    unknown

    Description

    Fan Rong, (male) . The effect of HIV-tat on the expression of DNA-PKcs.

    Country/Organization

    PR China/Beijing Institute of Radiation Medicine

    Type

    Article submitted to peer review journal

    Year

    2006

    Description

    Lynne Hampson*, Henry C Kitchener and Ian N Hampson. Specific HIV protease inhibitors inhibit the abilityof HPV16 E6 to degrade p53 and selectively killE6-dependent cervical carcinoma cells in vitro

    Country/Organization

    UK, University of Manchester, Gynaecological Oncology Laboratories

    Type

    Article in PLOS ONE

    Year

    October 2013 | Volume 8 | Issue 10 | e78411

    Publication URL

    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078411

    Description

    Analysis of Factors Contributing to the Low Survival ofCervical Cancer Patients Undergoing Radiotherapy inKenya

    Country/Organization

    1 University of Manchester, Viral Oncology, Research Floor, St Mary’s Hospital, Manchester, United Kingdom, 2 Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya, 3 Cancer Treatment Centre, Kenyatta National Hospital, Nairobi, Kenya, 4 Obstetrics and Gynaecology, Mansoura University Hospital, Cairo, Egypt

    Type

    Article submitted to peer review journal

    Year

    2005

    Description

    Sun Y, Xu QZ, Li JY, et al. Cloning of Tat gene of a HIV-1 B strain from Henan provence and homologous analysis of its encoding its encoding product. Letters in Biotechnology., 2005, 16: 245-248. (In Chinese)

    Country/Organization

    PR China/ Beijing Institute of Radiation Medicine

    Type

    Oral presentation at congress/meeting

    Year

    2011

    Description

    IPV, BERLIN, GERMANY September 2011: Paper Abstract: Maranga I.O, Hampson L, Oliver A, He X, Kitchener HC, Gichangi P, Rana F, Opiyo A, Hampson IN. Poor survival of cervical cancer patients undergoing radiotherapy in Kenya.

    Country/Organization

    UK, University of Manchester, Viral Oncology. Kenya, University of Nairobi, Obstetrics and Gynaecology

    Type

    PhD Thesis

    Year

    2006

    Description

    Sun Y. The studies of HIV Tat protein influencing cellular radiosensitivity and the acting mechanism.

    Country/Organization

    PR China/Beijing Institute of Radiation Medicine

    Type

    Article submitted to peer review journal

    Year

    2005

    Description

    Sun Y, Zhou PK. The effects of HIV-tat on cell cycle progression and expression of DNA repair gene. Journal of Toxicology., 2005, 19 (Supplement 3): 297-298 (In Chinese)

    Country/Organization

    PR China/ Beijing Institute of Radiation Medicine

    Type

    Presentation at national/international meeting

    Year

    2005

    Description

    Sun Y, Zhou PK. The effects of HIV-tat on cell cycle progression and the expression of DNA repair genes. Journal of Toxicology, 2005, 19 (Supplement 3): 297-298(In chinese).(This report obtained the award of the excellent presentation by young scientists in the 4th National Congress of the Chinese Society of Toxicology, September 18-21, 2005, in Shengyang )

    Country/Organization

    PR China/ Beijing Institute of Radiation Medicine /4th National Congress of the Chinese Society of Toxicology

    Type

    Presentation at national/international meeting

    Year

    2005

    Description

    Sun Y, Wang HP, Baibei, Huang YC, Sui JL and Zhou PK. Suppression of DNA-PKcs and radiosensitization in human fhabdomyosacoma cells by HIV-tat. The progressing of the 48th Annual Meeting of the Japan Radiation Research Society and the 1st Asian Congress of Radiation Research. Hiroshima, Japan. November 15-17, 2005, P129.

    Country/Organization

    PR China/Beijing Institute of Radiation Medicine / 48th Annual Meeting of the Japan Radiation Research Society and the 1st Asian Congress of Radiation Research. Hiroshima, Japan

    Type

    Article submitted to peer review journal

    Year

    2008

    Description

    Zhang SM, Sun Y, Fan R, Xu QZ, Liu XD, Wang Y, and Zhou PK. HIV-1 Tat interacts with and upregulates cyclin B1, and its involvement in apoptosis induction. (under submitted)

    Country/Organization

    PR China/ Beijing Institute of Radiation Medicine

    Type

    Oral presentation at congress/meeting

    Year

    2011

    Description

    IPV, BERLIN, GERMANY September 2011: Paper Abstract: Maranga I.O, Hampson L, Oliver A, He X, Kitchener HC, Gichangi P, Rana F, Hampson IN. HPV genotypes and HIV in cervical smears from Kenyan women

    Country/Organization

    UK, University of Manchester, Viral Oncology. Kenya, University of Nairobi, Obstetrics and Gynaecology

    Type

    Article submitted to peer review journal

    Year

    2006

    Description

    Sun Y, Huang YC, Xu QZ, Wang HP, Sui JL and Zhou PK. HIV-1 Tat protein inhibits repair of ionizing radiation-induced DNA double-strand breaks and increased cellular radio- sensitivity. Chinese Journal of Biochemistry and Molecular Biology., 2006, 22(8):666 -671.

    Country/Organization

    PR China/ Beijing Institute of Radiation Medicine

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