click here to download
Saturday, November 13, 2010
Diagnostic and Therapeutic Applications of Epigenetics
Epigenetic abnormalities, such as aberrant methylation of CpG islands, are inherited over cell
divisions, and play important roles in carcinogenesis. Aberrant methylation ofCpGislands specific
to tumor cells can be used as a marker to detect cancer cells or cancer-derived DNA, taking
advantage of the high sensitivity of methods to detect aberrant methylation. Methylations of
specific genes or methylation patterns of groups of genes were found to be associated with
responses to chemotherapeutics and prognosis. Methylation in non-cancerous tissues is now
attracting attention as a tumor risk marker, and is emerging as a target for cancer prevention.
Epigenetic alterations are potentially reversible. The use ofDNAdemethylating agents has turned
out to be effective for hematological malignancies, and is being tested in solid tumors. Histone
deacetylase inhibitors and methods for gene-specific epigenetic modification are being
developed. Application of epigenetics to cancer diagnostics and therapeutics, and possibly to
cancer prevention, is coming into clinics.
for more details click here
Epigenetics in cancer
Epigenetic mechanisms are essential for normal development and
maintenance of tissue-specific gene expression patterns in mammals.
Disruption of epigenetic processes can lead to altered gene
function and malignant cellular transformation. Global changes
in the epigenetic landscape are a hallmark of cancer. The initiation
and progression of cancer, traditionally seen as a genetic
disease, is now realized to involve epigenetic abnormalities along
with genetic alterations. Recent advancements in the rapidly
evolving field of cancer epigenetics have shown extensive reprogramming
of every component of the epigenetic machinery in
cancer including DNA methylation, histone modifications, nucleosome
positioning and non-coding RNAs, specifically microRNA
expression. The reversible nature of epigenetic aberrations has
led to the emergence of the promising field of epigenetic therapy,
which is already making progress with the recent FDA approval
of three epigenetic drugs for cancer treatment. In this review, we
discuss the current understanding of alterations in the epigenetic
landscape that occur in cancer compared with normal cells, the
roles of these changes in cancer initiation and progression, including
the cancer stem cell model, and the potential use of this knowledge
in designing more effective treatment strategies.
full article- click here
Friday, November 12, 2010
Wednesday, November 10, 2010
Tuesday, November 9, 2010
Gonadal effects of irradiation-Males
The testes are directly irradiated in the treatment of leukaemic relapse, tumours of the
lower pelvis and carcinoma in situ (CIS) of the testis. The germinal epithelium is highly sensitive
to irradiation and unlike most tissues is not spared by fractionation. The threshold dose for
effect is low, and with increasing dose there is a rapid increase in damage. The degree of risk will
be dose- and technique-dependent.
Transient suppression with subsequent recovery of spermatogenesis occurs with doses as
low as 0.5 Gy. Following 2–3 Gy there is a period of azoospermia after which full recovery is
expected within three years; at doses of 4–6 Gy recovery is not universal and may take up to five years; after 6 Gy there is a high risk of permanent sterility. Total body irradiation (TBI) with high-dose chemotherapy will sterilise men.
The Leydig cell is more resistant to irradiation. Nevertheless, a dose of irradiation in excess
of 15 Gy may be sufficient to affect Leydig cell function and production of testosterone, and a
dose of 24 Gy will irreversibly damage the Leydig cells in prepubertal boys.
When directly in the irradiation field the testes cannot be protected. The dose from
scattered irradiation from nearby beams can, however, be reduced by moving the gonad away
from the beam and, in some circumstances, by applying thick shielding cups directly over the
scrotum. Displacement of the scrotum away from lateral pelvic and proximal thigh fields with
taping during radiotherapy may be the most effective means available.
The beneficial effect of specific testicular shielding in reducing the dose from scattered
irradiation has been debated and depends on the position and nature of the radiation field.
Irradiation to the pelvic lymph node areas, as in the treatment of testicular tumours or lymphoma, results in a scattered dose to the testis of 1.5–3 Gy. In this situation, testicular shielding may be used and the dose reduced to the order of 0.5–0.8 Gy.11,12 Shielding placed directly on and around the scrotum is required and needs to be of a thickness to reduce an incident dose to 5% or less. The practical difficulties of this are considerable and the shield may impede the more effective measure of displacing the scrotum away from the beam, as described above.
courtesy-treatment on reproductive functions,Guidance on management
Report of a Working Party,November 2007.
Subscribe to:
Posts (Atom)