RADIO AND CHEMO SENSITIZATION DEPENDENCE ON OXYGEN
RADIO AND CHEMO SENSITIZATION DEPENDENCE ON OXYGEN
批准号:
3446480
负责人:
LAURIE A ROIZIN-TOWLE
金额:
$6.04万
依托单位国家:
美国
项目类别:
财政年份:
1983
资助国家:
美国
项目状态:
已结题
起止时间:
1983-07-01 至 1986-06-30
中文摘要
低氧细胞限制成功控制固体的可能性
英文摘要
The possibility that hypoxic cells limit the successful control of solid
tumors by x-rays has been recognized by radiation oncologists for more than
25 years. The realization that hypoxia may be a limiting factor in
chemotherapy is much more recent. Attempts to overcome the resistance of
hypoxic cells to radiotherapy have led to the development of "hypoxic cell
sensitizers", drugs that mimic oxygen and interact with radiation to
specifically increase the sensitivity of hypoxic cells. These sensitizers
preferentially kill hypoxic cells with a time-dependent cytotoxicity. This
cytotoxicity is the basis of the "preincubation effect" where prolonged
exposure of hypoxic cells to sensitizing drugs enhances their killing by
radiation and cancer chemotherapeutic agents. Exploitation of the
preincubation effect of these agents can be clinically advantageous where
lower doses of sensitizer can be used systemically to enhance the action of
radiation and chemotherapy drugs. The role of oxygen in this potentiation
is important because it may help to explain differences found between
animal and cell culture systems, and may mimic the intermediate levels of
oxygen expected to be found in solid tumors. Determination of the K factor
for radio- and chemo- sensitization would be of practical value in
evaluating the most effective use of these sensitizing compounds.
Experiments with mammalian cells of hamster and human origin are planned to
investigate and compare what levels of oxygen in a preincubation exposure
result in radio- and chemo- sensitization. Cells pretreated with several 2
and 4-nitroimidazoles will be subsequently exposed to increasing doses of
x-rays or Bleomycin, Cis-DDP, L-PAM, PALA, and BCNU. The plasma cell
membrane will also be analyzed as a target of the preincubation effect by
assaying for levels of Na, Kg Mg, and Ca-ATPase in pretreated cells. Use
of the preincubation effect, to enhance the killing of hypoxic cells
resistant to drug and radiation therapy, can make a significant
contribution in the treatment of solid tumors.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1007/978-3-642-75889-8_27
发表时间:
1990
期刊:
Current topics in microbiology and immunology
影响因子:
--
作者:
[M. Duyao;D. J. Kessler;D. Spicer;G. Sonenshein]
通讯作者:
M. Duyao;D. J. Kessler;D. Spicer;G. Sonenshein
HYPERTHERMIA STUDIES WITH HUMAN-DERIVED CARCINOMA CELLS
-
批准号:3185083
-
项目类别:
-
资助金额:$11.25万
-
财政年份:1986
-
负责人:LAURIE A ROIZIN-TOWLE
-
依托单位:
HYPERTHERMIA STUDIES WITH HUMAN-DERIVED CARCINOMA CELLS
-
批准号:3185081
-
项目类别:
-
资助金额:$10.9万
-
财政年份:1986
-
负责人:LAURIE A ROIZIN-TOWLE
-
依托单位:
HYPERTHERMIA STUDIES WITH HUMAN-DERIVED CARCINOMA CELLS
-
批准号:3185084
-
项目类别:
-
资助金额:$10.79万
-
财政年份:1986
-
负责人:LAURIE A ROIZIN-TOWLE
-
依托单位:
海外基金