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R Leake

Publications and source records attributed to R Leake.

At least 19 recordsLinked to original sources
PubMed2004

A prognostic index for operable, node-negative breast cancer.

Clinical data and samples from patients diagnosed, more than 10 years previously, with operable node-negative breast cancer (participants in the Scottish Adjuvant Tamoxifen trial), were revisited. Cases with two distinct categories of outcome were selected; more than 10 years disease-free survival ('good outcome') or distant relapse within 6 years of diagnosis ('poor outcome'). An initial set of cases was analysed for a range of putative prognostic markers and a prognostic index, distinguishing the two outcome categories, was calculated. This index was then validated by testing its predictive power on a second, independent set of cases. A combination of histological grade plus immunochemical staining for BCL-2, p27 and Cyclin D1, generated a useful prognostic index for tamoxifen-treated patients but not for those treated by surgery alone. The value of the index was confirmed in a second set of tamoxifen-treated, early stage breast cancers. Overall, it correctly predicted good and poor outcome in 79 and 74% of cases, respectively (odds ratio 11.0). Other markers assessed added little to prediction of outcome. In the case of molecular assays, sensitivity and reliability were compromised by the age of the tissue specimens and the variability of fixation protocols. In selecting patients for adjuvant systemic chemotherapy, the proposed index improves considerably on current international guidelines and matches the performance reported for 'gene-expression signature' analysis.

Biomarkers, Tumor↗
PubMed2000

Detection of the oestrogen receptor (ER). immunohistochemical versus cytosol measurements.

Oestrogen receptor (ER) content gives a direct indication of the chances that a breast cancer patient will show a sustained response to endocrine therapy. Thus, an ER value should be recorded for every breast cancer patient. ER was traditionally measured by a ligand binding assay (LBA). LBA is not suitable for all routine hospitals in which breast cancer is treated. More appropriate is immunohistochemistry (IHC). This paper identifies advantages and disadvantages of both assays, suggests that both methods predict equally response to endocrine therapies and describes a simple, semi-quantitative IHC for which external quality assurance works successfully.

Biomarkers, Tumor↗
PubMed2000

Immunohistochemical detection of steroid receptors in breast cancer: a working protocol. UK Receptor Group, UK NEQAS, The Scottish Breast Cancer Pathology Group, and The Receptor and Biomarker Study Group of the EORTC.

The biochemical assay for the oestrogen receptor has shown the clinical value of knowing the concentration of the receptor within tissue. The immunohistochemical assay is rapidly taking over from the biochemical assay. Therefore, it is vital to have an equivalent scoring system that will have the same predictive value. This paper reports both a practical protocol and a scoring system that should achieve this aim. This approach should be applicable to many more biomarkers detected by immunohistochemistry.

Biomarkers, Tumor↗
PubMed2000

Twenty years of experience with the steroid receptor external quality assessment program - the paradigm for tumour biomarker EQA studies. On behalf of the EROTC Receptor and Biomarker Study Group.

Estrogen receptor (ER) assays have clinical relevance in selecting women who would benefit from endocrine intervention. As the degree of benefit from endocrine therapy is directly related to the quantity of receptor present in the tumour, the quality of the steroid receptor assays is important. Moreover, since patients entered in multi-centre trials often include stratification based on the receptor status, receptor assays should be comparable between different institutes. ER- and progesterone receptor (PgR)-assays have been evaluated in quality assessment studies for almost 20 years by the EORTC Receptor and Biomarker Study Group. This study analyses our findings over these years and concludes with a recommended minimum structure on which QA schemes for any biomarker could be based.

Biomarkers, Tumor↗
PubMed1999

Improving adjustment to chronic illness through strategic self-presentation: an experimental study on a renal dialysis unit.

Laboratory studies show that strategic self-presentations strongly influence private self-evaluations. The present study experimentally manipulated self-presentations of dialysis patients' coping skills in order to influence their adjustment. In all, 42 renal dialysis patients matched for diabetes, gender, and dialysis years were randomly assigned to 3 conditions; adjustment was assessed at baseline, post-intervention, and 1 month follow-up. Patients in a self-presentation condition selectively presented themselves as successful copers in a videotaped interview, ostensibly as part of a training program for new patients. Patients in a problem disclosure condition discussed problems with managing their illness. Control group patients viewed a medical videotape about adjusting to dialysis. Patients in the self-presentation condition reported better adjustment, fewer physical symptoms, and more coping skills 1 month later, compared with patients in the other 2 conditions. In addition, coping skills were shown to mediate the relationship between strategic self-presentation and adjustment.

Adaptation, Psychological↗
PubMed1999

Current licensure for acupuncture in the United States.

This article reviews current licensure and certification standards for the practice of acupuncture in the United States. It serves as a current reference for the regulation of the practice of acupuncture, the licensing of acupuncturists, and the certification and training of physicians, chiropractors, dentists, podiatrists, and naturopathic physicians to practice acupuncture. Two national accreditation bodies are responsible for certifying acupuncture training and practice. The Accreditation Commission of Acupuncture and Oriental Medicine establishes accreditation criteria and curriculum evaluation of acupuncture training programs. The National Certification of Acupuncture and Oriental Medicine certifies individuals to practice acupuncture in the United States. Although national standards have been established, regulations regarding training and the practice of acupuncture are determined individually by each state, and tend to vary widely. Typical acupuncture training curricula for physicians and chiropractors are discussed, and variations in training requirements by state for acupuncturists and each of the other 5 disciplines is provided.

Acupuncture Therapy↗
PubMed1999

Contents of HRT and mechanisms of action.

Formulation of HRT preparations has changed very significantly over the last few decades. The problems of unopposed oestrogens are now well recognised. Addition of progestins may overcome these problems in some target tissues. However, there is clear evidence for differential effects of both steroids in different target tissues. It is also vital to be clear on the dose-response to each steroid in each target tissue. Steroids given orally may undergo different metabolism from those given transdermally or subcutaneously. This can mean that, even given dose for dose, there can still be differences in the regulation of, for example, lipid profiles, depending on delivery route. The situation is further complicated by the discovery that there is more than one receptor for each steroid. Steroid receptors are members of the super-family of nuclear receptors. Steroid enters the cell, binds and activates empty receptors, inducing dimerisation and acquisition of high affinity for specific sequences of nucleotides within the hormone-response elements (HRE) of the target genes. Hormone-receptor complex interacts with the HRE to modulate transcription of the gene. The different receptors for each steroid (e.g. oestrogen receptors alpha and beta) help promote the differential responses in different target tissues. Analysis of the overall responses to HRT requires a knowledge of the dose and specificity of each steroid within the formulation, together with an understanding of how each steroid regulates the activities of each sub-group of receptors in each target tissue, allowing for the appropriate metabolism of the primary steroids. Additionally, there will be variations among different individuals.

Chemistry, Pharmaceutical↗
PubMed1996

The cell cycle and regulation of cancer cell growth.

There are two points (brake-points) through which the cell must pass before it can enter cell division. Progress through each brake-point requires the presence of an active cyclin-dependent kinase (Cdk). There are specific cyclins to activate the Cdk's at different parts of the cell cycle. Activation of the cyclin-Cdk complex is tightly regulated by the phosphorylation state of the Cdk. Exogenous growth stimulators (hormones, growth factors, and cytokines) all work through an intracellular kinase cascade that drives the production and activation of early nuclear proteins that, in turn, induce transcription of the genes for cyclins, Cdk's, and other cell cycle regulators. Retinoblastoma protein regulates cell division by inactivating specific growth-promoting proteins. Therefore, mutation of the Rb gene can lead to uncontrolled cell division and thus promotion of transformed cells. p53 protein will prevent replication of cells with damaged DNA. Hence, transformed cells can only readily progress to tumors if the p53 gene is mutated in a manner that inactivates the protein product. Members of the bcl-2 family act, in homodimers and heterodimers, to shunt cells either into cell division or into apoptosis. Understanding the mechanisms by which the balance of cell cycle: apoptosis can be manipulated will lead to new ways of controlling abnormal cellular growth. Most aspects of cellular function reflect changes in phosphorylation of critical serine, threonine, and tyrosine residues on the relevant regulatory proteins. The kinases the phosphatases involved are themselves under tight control.

Animals↗
PubMed1995

Production of transforming growth factor-alpha by normal and polycystic ovaries.

The mechanism of anovulation in polycystic ovary (PCO) syndrome remains unknown. As circulating concentrations of FSH are apparently normal, and in vivo, granulosa cells from anovulatory PCO are hyperresponsive to FSH, it has been suggested that the lack of follicular development in anovulatory PCO is caused by overexpression of a paracrine growth factor that inhibits steroidogenesis. Epidermal growth factor and the structurally homologous transforming growth factor-alpha (TGF alpha) are suitable candidates for this role, but although the production of the latter has been demonstrated in the ovary, no comparison has been performed between the levels in normal ovaries and PCO. We compared the levels of TGF alpha in follicular fluid and in granulosa cell- and theca- and stroma-conditioned media from normal ovaries and PCO. TGF alpha was present in the range of 0.2-200 ng/mL in follicular fluid. There was a significant inverse correlation of TGF alpha with follicle size, with no differences between follicles from normal ovaries and PCO. Granulosa cell-conditioned medium contained concentrations of TGF alpha ranging from 0.1-200 ng/1000 cells. There was a wide range of concentrations in theca- and stroma-conditioned media, with levels varying from 0.2-100 ng/mg tissue and no consistent effect of LH. There were no significant differences between the levels from normal ovaries or PCO in medium conditioned by any compartment of the ovary. We conclude that the failure of folliculogenesis in PCO syndrome is not likely to be due to overproduction of TGF alpha by the ovary.

Anovulation↗
PubMed1992

The prognosis of breast cancer patients in relation to the oestrogen receptor status of both primary disease and involved nodes.

Nodal involvement is accepted as the best single marker of prognosis in breast cancer. However, there is little information on the sub-division of node-positive patients according to the oestrogen receptor status of the nodal tissue. We have previously reported (Eur. J. Ca. 1987, 23, 31) that, in almost all cases, involved nodes are only oestrogen receptor positive (ER+) in patients whose primary tumours are uniformly ER+. This paper presents clinical follow-up on a larger group of patients with node positive breast cancer. For each patient, both soluble and nuclear receptor concentrations were determined in three separate parts of the primary tumour and in at least one involved node (we have previously defined tumours which contained ER in all six fractions of the primary as HS++, those lacking receptor in some fractions as HS+- and wholly receptor negative tumours as HS--). Median follow-up time was 71.5 months. As expected, patients whose tumours were HS++ had a significant (P less than 0.008) survival advantage. More importantly, patients with ER in both the soluble and nuclear fractions of their involved nodes survived significantly (P less than 0.003) longer than those with ER- nodes. Thus, full oestrogen receptor status of involved nodes will give sufficient prognostic information when adequate primary tissue is not available.

Biomarkers, Tumor↗
PubMed1991

A multicentre study into the reliability of steroid receptor immunocytochemical assay quantification. British Quality Control Group.

Qualitative and semiquantitative assessments of oestrogen receptor and progesterone receptor positivity determined on previously immunocytochemically stained slides were performed by eight independent assessors. Concordance between assessments of steroid receptor status was good (24/25, 96%). Interassessor variations in estimates of positive immunostaining levels were high, varying by between 10 and 75% for individual slides. In 2 cases estimates for the same section ranged between 15% nuclei positive and 90% nuclei positive. Wide variations were also recorded for slides stained for progesterone receptors. Results using an assessment procedure combining staining intensity and percentage positivity estimates were also subject to marked discordance. A computerised image analysis system, also used to assess slides gave results similar to the mean manually determined percentage positivity values. It is suggested that quality control of steroid receptor immunocytochemical quantification be considered and that automated image analysis may represent an accurate and valid means of achieving this.

Breast Neoplasms↗