Search Results

You are looking at 101 - 110 of 431 items for :

  • "oestrogen" x
  • Refine by access: All content x
Clear All
M Dowsett Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by M Dowsett in
Google Scholar
PubMed
Close
,
C Archer Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by C Archer in
Google Scholar
PubMed
Close
,
L Assersohn Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by L Assersohn in
Google Scholar
PubMed
Close
,
R K Gregory Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by R K Gregory in
Google Scholar
PubMed
Close
,
P A Ellis Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by P A Ellis in
Google Scholar
PubMed
Close
,
J Salter Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by J Salter in
Google Scholar
PubMed
Close
,
J Chang Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by J Chang in
Google Scholar
PubMed
Close
,
P Mainwaring Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by P Mainwaring in
Google Scholar
PubMed
Close
,
I Boeddinghaus Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by I Boeddinghaus in
Google Scholar
PubMed
Close
,
S R Johnston Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by S R Johnston in
Google Scholar
PubMed
Close
,
T J Powles Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by T J Powles in
Google Scholar
PubMed
Close
, and
I E Smith Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.

Search for other papers by I E Smith in
Google Scholar
PubMed
Close

The interaction between cell death and cell proliferation determines the growth dynamics of all tissues. Studies are described here which relate the changes in proliferation and apoptosis that occur in human breast cancer during medical therapeutic manoeuvres. Xenograft studies strongly support the involvement of increased apoptosis as well as decreased proliferation after oestrogen withdrawal, and limited studies in clinical samples confirm the involvement of both processes. Cytotoxic chemotherapy induces increases in apoptosis within 24 h of starting treatment. However, after 3 months therapy the residual cell population shows apoptotic and proliferation indices much below pretreatment levels. Further molecular studies of this "dormant" population are important to characterise the mechanism of their resistance to drug therapy. The early changes in proliferation and apoptosis may provide useful intermediate response indices.

Free access
M Dowsett Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK.

Search for other papers by M Dowsett in
Google Scholar
PubMed
Close

The clinical development of aromatase inhibitors has been largely confined to postmenopausal breast cancer patients and strongly guided by pharmacological data. Comparative oestrogen suppression has been helpful in circumstances in which at least one of the comparitors has caused substantially non-maximal aromatase inhibition. However, the triazole inhibitors, letrozole and anastrozole, and the steroidal inhibitor, exemestane, all cause >95% inhibition. Comparisons between these drugs therefore require more sensitive approaches such as the direct measurement of enzyme activity by isotopic means. None of these three agents has significant effects on other endocrine pathways at its clinically applied doses. Pharmacokinetic analyses of the combination of tamoxifen and letrozole have revealed that these drugs interact, resulting in letrozole concentrations approximately 35-40% lower than when letrozole is used alone.

Free access
S Cleator Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. scleator@icr.ac.uk

Search for other papers by S Cleator in
Google Scholar
PubMed
Close
,
M Parton Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. scleator@icr.ac.uk

Search for other papers by M Parton in
Google Scholar
PubMed
Close
, and
M Dowsett Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. scleator@icr.ac.uk

Search for other papers by M Dowsett in
Google Scholar
PubMed
Close

Neoadjuvant/pre-surgical medical therapy of breast cancer provides a unique opportunity to derive biological information related to tumour response. Large clinical trials of neoadjuvant chemotherapy have established that pathological complete remission is an independent predictor of improved disease-free survival. Clinical response has been found to parallel substantial reductions in the proliferation of breast cancer cells. Increased apoptosis also occurs, but it is not closely associated with response. Numerous biological markers such as p53, bcl-2, oestrogen receptor (ER) and HER2 have been assessed for their possible role in chemoresistance/response, but the data are not clear at this stage. Continuing work using cDNA microarrays may yield new, more reliable indices of likely response and an improved insight into biological processes related to chemotherapeutic response.

Free access
M Baum
Search for other papers by M Baum in
Google Scholar
PubMed
Close
Restricted access
R C F Leonard
Search for other papers by R C F Leonard in
Google Scholar
PubMed
Close
,
A Ray
Search for other papers by A Ray in
Google Scholar
PubMed
Close
,
L Lee
Search for other papers by L Lee in
Google Scholar
PubMed
Close
,
T Leonard
Search for other papers by T Leonard in
Google Scholar
PubMed
Close
, and
P Hopwood
Search for other papers by P Hopwood in
Google Scholar
PubMed
Close
Restricted access
R Sainsbury
Search for other papers by R Sainsbury in
Google Scholar
PubMed
Close
Restricted access
J Marsden
Search for other papers by J Marsden in
Google Scholar
PubMed
Close
and
N P M Sacks
Search for other papers by N P M Sacks in
Google Scholar
PubMed
Close
Restricted access
Restricted access
R D Bulbrook
Search for other papers by R D Bulbrook in
Google Scholar
PubMed
Close
,
B S Thomas
Search for other papers by B S Thomas in
Google Scholar
PubMed
Close
, and
D Y Wang
Search for other papers by D Y Wang in
Google Scholar
PubMed
Close
Restricted access
M Dowsett
Search for other papers by M Dowsett in
Google Scholar
PubMed
Close
Restricted access