PubMed Health⌕ Search

Biomedical subjects

I O Ellis

Publications and source records attributed to I O Ellis.

At least 55 records · Page 3Linked to original sources
PubMed2003

A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma.

BACKGROUND: The aim of this study was to determine in a randomised trial whether there is any significant difference in toxicity between modified CHOP and MCOP chemotherapy in elderly patients with aggressive non-Hodgkin's lymphoma (NHL) and to determine whether this reduced dose chemotherapy can be administered with full dose intensity, low toxicity and produce acceptable survival. PATIENTS AND METHODS: Between 1993 and 2000, 155 eligible patients were randomised into this trial mainly from three centres (Nottingham, Birmingham and Leeds, UK). The patients were newly diagnosed with aggressive NHL and had a median age of 74 years (range 65-91 years). Ninety-six patients (62%) had bulky stage I or II disease; 59 patients (38%) had either stage III or IV disease; 77% had one or more extranodal sites involved at presentation; and 31% showed B symptoms. Seventy-seven patients were randomised to receive six cycles of modified CHOP (cyclophosphamide 600 mg/m(2) i.v., doxorubicin 30 mg/m(2) i.v., vincristine 1 mg i.v. all on day 1 with prednisolone 20 mg bd for days 1-5) every 21 days and 78 patients to MCOP (mitozantrone 10 mg/m(2) i.v. substituted for doxorubicin). Growth factors were not used routinely. After completion of chemotherapy, 39 patients received involved field radiotherapy (35-40 Gy) in 20 fractions. RESULTS: One hundred and one patients (65%) completed all six cycles of chemotherapy. The median course dose intensity was 97%. The median follow-up for 53 surviving patients was 51 months. The median survival was 19 months (95% confidence interval 10-36 months) with an actuarial survival of 47% at 2 years and 42% at 3 years (CHOP versus MCOP, P = 0.79). There was no significant difference in any of the toxicities experienced with either CHOP or MCOP, except for white cell count (46 patients on MCOP and 27 patients on CHOP had grade 3 or 4 toxicity, P = 0.002) and red cell transfusion (37 patients, MCOP; 17 patients, CHOP; P = 0.001). Grade 3 or 4 neutropenia was documented in 75 patients (50%). One patient died from toxicity whilst in remission and seven patients died with septicaemia and persistent NHL. CONCLUSION: This multicentre randomised trial provides further information on the dose intensity achievable with CHOP or MCOP regimens in elderly patients (median age 74 years) with aggressive NHL. These dose-reduced regimens can be given with nearly 100% dose intensity with 65% of patients completing all the treatment. Survival is comparable to that observed with the more intensive regimens given in this age group.

Administration, Oral↗
PubMed2003

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 5 cases.

Five cases of a hitherto undescribed breast tumor having histologic features similar to those of the tall cell variant papillary thyroid carcinoma are described. They were composed of columnar mitochondrion-rich to oxyphilic cells arranged in nests, papillae, and follicle-like structures. In addition, the neoplastic cells showed numerous nuclear grooves and, in two cases, nuclear pseudo-inclusions. None of the patients had previous concomitant or subsequent evidence of a thyroid tumor. Immunohistochemistry further excluded a metastasis from the thyroid in the four cases tested, as they were consistently thyroglobulin and thyroid transcription factor 1 negative.

Aged↗
PubMed2003

X-ray refraction effects: application to the imaging of biological tissues.

The purpose of this study was to explore the potential of refraction contrast X-ray imaging of biological tissues. Images of dissected mouse lungs, heart, liver and legs were produced using the medical beamline at the Elettra Synchrotron at Trieste, Italy. The technique used was diffraction enhanced imaging. This utilizes a silicon crystal positioned between the tissue sample and the detector to separate refracted X-rays from transmitted and scattered radiation by Bragg diffraction. The contrast in the images produced is related to changes in the X-ray refractive index of the tissues, resulting in remarkable clarity compared with conventional X-ray images based on absorption effects. These changes were greatest at the boundaries between different tissues, giving a marked edge enhancement effect and three-dimensional appearance to the images. The technique provides a way of imaging a property of biological tissues not yet exploited, and further studies are planned to identify specific applications in medical imaging.

Animals↗
PubMed2002

HER-2 in breast cancer--methods of detection, clinical significance and future prospects for treatment.

The Human Epidermal Growth Factor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the Epidermal Growth Factor Receptor (EGFR) which is the prototypal member of this family of receptor tyrosine kinases. HER-2 gene amplification is found in 20-30% of breast cancers. Various methods such as immunohistochemistry, southern and slot blotting, enzyme immunoassays and fluorescence in situ hybridization have all been employed to evaluate HER-2 gene and protein abnormalities. Of these immunohistochemistry is the most frequently employed but there are valid indications for the other avaliable methods. However, it is prudent that whichever methods employed are standardized, especially those that possess may have a degree of subjectivity in their assesment.

Animals↗
PubMed2002

Neuroendocrine differentiation and prognosis in breast adenocarcinoma.

AIMS: Neuroendocrine differentiation has been detected, and its prognostic value studied, in a number of common human carcinomas. To date there are few detailed studies examining its relevance in breast carcinoma. In this study we evaluate the frequency and prognostic importance of neuroendocrine differentiation in breast adenocarcinoma. METHODS AND RESULTS: The presence of neuroendocrine differentiation, defined as positive reactivity for three markers, neuron-specific enolase (NSE), chromogranin A and/or synaptophysin, has been evaluated in 99 patients with primary operable breast cancer using standard immunocytochemical techniques. A consecutive cohort of patients were selected from the Nottingham/Tenovus series. Comprehensive patient and tumour records have been maintained, and patients were followed up according to a defined protocol. Eighteen cases were positive for NSE, 10 for chromogranin A and 13 for synaptophysin. Eleven percent were positive with more than one neuroendocrine marker. No significant association was found between neuroendocrine differentiation and tumour size, grade, stage or the prevalence of vascular invasion. There was no significant difference in either overall or disease-free survival between patients with or without neuroendocrine differentiation. CONCLUSIONS: In this study we confirm that neuroendocrine differentiation can be identified in a subset (10-18%) of human breast carcinomas. This phenomenon appears to have no relationship to established prognostic factors or patient outcome.

Adenocarcinoma↗
PubMed2002

An integrated approach utilizing artificial neural networks and SELDI mass spectrometry for the classification of human tumours and rapid identification of potential biomarkers.

MOTIVATION: MALDI mass spectrometry is able to elicit macromolecular expression data from cellular material and when used in conjunction with Ciphergen protein chip technology (also referred to as SELDI-Surface Enhanced Laser Desorption/Ionization), it permits a semi-high throughput approach to be taken with respect to sample processing and data acquisition. Due to the large array of data that is generated from a single analysis (8-10000 variables using a mass range of 2-15 kDa-this paper) it is essential to implement the use of algorithms that can detect expression patterns from such large volumes of data correlating to a given biological/pathological phenotype from multiple samples. If successful, the methodology could be extrapolated to larger data sets to enable the identification of validated biomarkers correlating strongly to disease progression. This would not only serve to enable tumours to be classified according to their molecular expression profile but could also focus attention upon a relatively small number of molecules that might warrant further biochemical/molecular characterization to assess their suitability as potential therapeutic targets. RESULTS: Using a multi-layer perceptron Artificial Neural Network (ANN) (Neuroshell 2) with a back propagation algorithm we have developed a prototype approach that uses a model system (comprising five low and seven high-grade human astrocytomas) to identify mass spectral peaks whose relative intensity values correlate strongly to tumour grade. Analyzing data derived from MALDI mass spectrometry in conjunction with Ciphergen protein chip technology we have used relative importance values, determined from the weights of trained ANNs (Balls et al., Water, Air Soil Pollut., 85, 1467-1472, 1996), to identify masses that accurately predict tumour grade. Implementing a three-stage procedure, we have screened a population of approximately 100000-120000 variables and identified two ions (m/z values of 13454 and 13457) whose relative intensity pattern was significantly reduced in high-grade astrocytoma. The data from this initial study suggests that application of ANN-based approaches can identify molecular ion patterns which strongly associate with disease grade and that its application to larger cohorts of patient material could potentially facilitate the rapid identification of validated biomarkers having significant clinical (i.e. diagnostic/prognostic) potential for the field of cancer biology. AVAILIBILITY: Neuroshell 2 is commercially available from ward systems.

Astrocytoma↗
PubMed2001

Phosphorylation of ERK1/2 mitogen-activated protein kinase is associated with poor response to anti-hormonal therapy and decreased patient survival in clinical breast cancer.

It is believed that growth factor phosphorylation cascades interact closely with oestrogen receptor (ER) signaling to regulate breast cancer growth, and that alterations in these pathways may underlie resistance to anti-hormones such as tamoxifen. There is an increasing body of experimental evidence implicating the mitogen-activated protein kinase extracellular signal-regulated-kinases ERK1 and ERK2 (ERK1/2 MAPK) in these events. The present study is the first to address the relationship between ERK1/2 MAPK phosphorylation (p-MAPK) and response to anti-hormonal agents in clinical breast cancer (n = 90). Immunocytochemical analysis using a phosphorylation state-specific ERK1/2 MAPK antibody revealed 72% of breast tumors to have considerable nuclear p-MAPK immunostaining (designated p-MAPK positive), whereas staining was barely detectable or absent in the remaining 28% (designated p-MAPK negative). Comparison with staining in normal breast material obtained from reduction mammoplasty patients (n = 10) demonstrated an increased frequency of higher intensity p-MAPK immunostaining cells within carcinomas (p = 0.002). Significant relationships were revealed between p-MAPK positivity and poorer quality (p = 0.001) and shortened duration (p = 0.006) of anti-hormonal response, as well as with decreased survival time from the initiation of therapy (p = 0.022). These associations were retained in ER positive disease (p = 0.013, p = 0.037 and p = 0.048 respectively), where multivariate analysis demonstrated p-MAPK status to be a significantly independent predictor for response duration (p = 0.034) and patient survival (p = 0.029). Phosphorylated ERK1/2 MAP kinase is thus potentially prognostic for prediction of response to anti-hormonal agents and survival, data providing further evidence that ERK1/2 MAP kinase plays a role in circumvention of anti-hormonal response in breast cancer.

Adult↗
PubMed2001

Growth pattern of ductal carcinoma in situ (DCIS): a retrospective analysis based on mammographic findings.

The aim of this study was to obtain information concerning the direction and rates of growth of ductal carcinoma in situ (DCIS). The previous mammograms of 124 women diagnosed with DCIS were examined. If in retrospect calcifications were present on the previous examination, the exact size and position were recorded on both diagnostic and previous imaging. The rates of change and direction of change in extent of calcifications were calculated. 39 women with a diagnosis of DCIS in retrospect had calcifications visible on both their current and prior examinations; these formed the study group. For individual clusters of calcification, change occurred along an axis to the nipple at a mean of 5.5 mm y(-1)and along an axis at 90 degrees to the nipple at 2.6 mm y(-1). Increase in calcifications along the axis to the nipple occurred at 2.6 mm y(-1)toward and 2.8 mm y(-1)away from the nipple. Increase in the axis to the nipple occurred at 1.8 mm y(-1)for low grade, 4.2 mm y(-1)for intermediate grade and 7.1 mm y(-1)for high grade. DCIS growth along an axis to the nipple occurs at over twice the rate of growth in the other direction(s) and growth toward and away from the nipple occurred equally. Growth rates increased with increasing nuclear grade of DCIS. These results validate nuclear grading of DCIS. Additionally, the results suggest that increased importance should be placed on identifying the 'nipple' and 'anti-nipple' margins of DCIS represented by calcifications for both surgical excision and pathological scrutiny.

Breast Neoplasms↗
PubMed2001

Effect of dietary GLA+/-tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts.

Gamma linolenic acid (GLA) possesses a number of selective anti-tumour properties including modulation of steroid receptor structure and function. We have investigated the effect of dietary GLA on the growth, oestrogen receptor (ER) expression and fatty acid profile of ER+ve human breast cancer xenografts. Experimental diets A, B, C, D were commenced after subcutaneous implantation of 40 female nude mice with the MCF-7 B1M cell line (Group A = control diet: B = control diet + GLA supplement: C = control diet + tamoxifen: D = control diet + GLA + tamoxifen; 10 mice/group). The mice were terminated when tumour cross-sectional area reached 250 mm(2). ER H-scores were assessed by immunohistochemical assay and fatty acid profiles by gas-liquid chromatography of termination tumour samples. Groups C and D displayed significantly slower tumour growth (p =.0002, p =.0006) with trend for slower growth in B (p =.065) compared to control Group A. ER was significantly reduced in all groups compared to A (p <.0001) with Group D (combined therapy) displaying markedly lower ER expression than with either therapy alone (p =.0002). There were significantly raised levels of tumour GLA and metabolites in the two groups (B and D) receiving GLA (p <.0001). This xenograft model of ER+ve breast cancer has demonstrated significantly lower tumour ER expression in those groups receiving GLA, an effect which appears to be additive to the reduced ER expression resulting from tamoxifen alone. The effects of GLA on ER function and the possibility of synergistic inhibitory action of GLA with tamoxifen via enhanced down-regulation of the ER pathway require further investigation.

Animals↗
PubMed2001

Pathological validation and significance of micrometastasis in sentinel nodes in primary breast cancer.

In embracing a multidisciplinary approach to the management of patients with sentinel node biopsy in breast cancer, the pathologist task is to screen sentinel nodes for possible metastasis. The consequences of missing sentinel node micrometastasis can directly influence treatment strategies, and this screening therefore has to be performed with more attention than usual. There is presently great diversity in the histopathological work-up of sentinel nodes, with many centres employing additional techniques such as immunohistochemistry, reverse transcription polymerase chain reaction or flow cytometry in addition to routine haematoxylin and eosin staining. In this review, we address the pathological validation and significance of micrometastasis in sentinel node biopsy in primary breast cancer.

Breast Neoplasms↗
PubMed2001

Prognostic significance of synchronous and metachronous bilateral breast cancer.

Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast, but the clinical significance of this development is unclear. The purpose of this study was to assess the impact of synchronous bilateral breast cancer or the development of a metachronous contralateral breast primary on the prognosis. In a series of 3210 women age < or = 70 years treated between 1975 and 1995 for primary operable breast cancer, 106 were identified to have bilateral breast cancer. Of these women, 26 were noted to have synchronous bilateral breast primaries (0.8%), and 80 developed a contralateral breast cancer after treatment for an initial primary breast cancer. Using life-tables analysis, there was a significant difference in survival between women with unilateral breast cancer, those with synchronous bilateral breast cancers, and those with metachronous contralateral breast with survivals at 16 years of 53.8%, 42.4%, and 60.1%, respectively (p < 0.0001), from the date of the diagnosis of the first primary tumor. There was no difference in survival seen between the three groups when survival was calculated from the date of diagnosis of the second primary in cases of metachronous contralateral breast cancer (p = 0.31). When contralateral breast cancer was incorporated as a time-dependent covariate in a Cox multivariate model together with the three factors used to determine the Nottingham Prognostic Index (invasive tumor size, grade, and lymph node stage), contralateral breast cancer continued to be a significant prognostic determinant (p = 0.02). The survival of women with synchronous bilateral breast cancer or metachronous breast cancers diagnosed within 2 years of the original primary was worse than those with unilateral disease. However, the time duration to metachronous contralateral breast cancer did not have prognostic significance in a multivariate model compared with the prognostic features of the original primary.

Adult↗
PubMed2001

Sentinel node biopsy for breast cancer may have little to offer four-node-samplers. results of a prospective comparison study.

The aims of the study were to determine how often four node axillary sampling (4NAS) encompasses the sentinel node (SN) and to compare the relative sensitivity of 4NAS with sentinel node biopsy (SNB) for axillary node staging. 200 patients with breast cancer were preoperatively injected with 27 MBq 99m-Tc-labelled colloid adjacent to the tumour. At operation, standard 4NAS was performed. Each node was counted ex vivo using a probe. A search was then made to find a node with higher counts in vivo directed by the probe. If found, it was excised. Each node was submitted separately to pathology. A SN was identified in 191 patients (96%). The SN was contained in the 4NAS in 153 patients (80%) and identified separately in 38 patients (20%). Of 60 node-positive patients, 49 were positive by 4NAS and SNB, the SN was not identified in 2 and in 8 the SN was falsely negative compared with 4NAS. For 1 patient, the SN was positive and the 4NAS negative. SNB performed using radiolabelled colloid has no advantage over 4NAS when nodes are assessed by standard histological technique.

Axilla↗
PubMed2001

Mammographic size of ductal carcinoma in situ does not predict the presence of an invasive focus.

A proportion of women thought to have ductal carcinoma in situ (DCIS) on mammography and a core biopsy showing DCIS only, in fact have an invasive focus on surgical excision. This study aims to identify the percentage of such patients who harbour an invasive focus and to ascertain features which can predict the presence of invasion. 140 patients had a core biopsy diagnosis of DCIS without invasion. All patients had their core biopsy graded and mammography was performed on 128 patients. Mammographic findings were classified by a radiologist blinded to the surgical findings into normal, mass/distortion or microcalcification. The extent of the microcalcifications was measured. The core biopsies were graded into high, intermediate or low grade DCIS groups. The core biopsy and radiological findings were compared to see if they could predict the presence of invasive disease at surgical excision. Of the 140 patients, 61 (44%) had an invasive focus. 8 (47%) of 17 patients with normal mammography had an invasive focus. 4 (36%) of 11 patients with a mammographic mass had evidence of invasion. Of the 100 patients with mammographic microcalcifications 48 (48%) had an invasive focus. In the 10 patients with low grade DCIS on core biopsy, 3 (30%) had an invasive focus. Comparative studies in patients with intermediate and high grade DCIS, were 7 of 18 (39%) and 51 of 112 (46%), respectively. Thus, 44% of women thought to have DCIS only on preoperative investigation had an invasive focus. In contrast to previous expressed opinions, neither mammography or grade were predictive. We have not identified any factor capable of predicting a higher likelihood of an invasive focus.

Adult↗
PubMed2001

Change in expression of ER, bcl-2 and MIB1 on primary tamoxifen and relation to response in ER positive breast cancer.

Pre-treatment oestrogen receptor (ER) expression in breast cancer predicts for rate of response to endocrine therapy but not for the quality or duration of response (DofR). ER is known to be down-regulated by anti-oestrogens. This study has tested the hypothesis that the degree of down-regulation of ER and the ER-regulated marker bcl-2 are associated with the quality and duration of tamoxifen response. 80 patients with ER+ve breast cancer (H-score > 10) receiving primary tamoxifen (n = 51 Stage I-II elderly; n = 29 Stage III) underwent sequential tumour biopsies for immunocytochemical assessment of ER, bcl-2 and the proliferation marker MIB1. Median follow-up is 45 months. By 6-months on therapy three patients had attained complete response (CR), 27 partial response (PR); 44 static disease (SD) and six progression (PD) by UICC criteria. Greater decrease in ER and bcl-2 H-score from pre-treatment to 6 weeks (p = 0.035, p = 0.037) and ER and bcl-2 H-score from pre-treatment to 6 months (p = 0.058, p = 0.036) were significantly associated with better quality of response (CR/PR vs SD/PD). Greater 6-week and 6-month reduction in bcl-2 H-score (p = 0.041, p = 0.036) and 6-week reduction in MIB1 (p = 0.013) were significantly correlated with longer DofR. This study demonstrates that greater down-regulation of ER and the ER-regulated protein bcl-2 on primary tamoxifen are significantly associated with a better quality of response and bcl-2 and the proliferation marker MIB1 a longer duration of response in ER+ve breast cancer.

Aged↗
PubMed2001

Extent of ductal carcinoma in situ within and surrounding invasive primary breast carcinoma.

BACKGROUND: The aim of this study was to evaluate the pathological and morphological features of ductal carcinoma in situ (DCIS) within and surrounding invasive ductal carcinoma, and to investigate its relationship with clinical outcome and established prognostic variables. METHODS: One hundred and seven patients with primary operable invasive breast carcinoma and associated DCIS treated by simple or subcutaneous mastectomy or wide local excision with radiotherapy were assessed. Those with pure DCIS and insufficient tumour available for examination were excluded. The most representative haematoxylin and eosin-stained sections from the remaining 91 samples were selected and examined at x 100 magnification using a 45-point, 2-mm grid graticule. The entire section was assessed and the cell under each point of the graticule was classed as either normal (a), DCIS surrounded by normal tissue (b), invasive tumour (c) or DCIS surrounded by invasive malignancy (d). The volume ratio of DCIS in the normal (b/(a + b)) and invasive (d/(c + d)) tissue was then calculated. RESULTS: The DCIS volume within invasive tumour was not associated with outcome. The DCIS volume within adjacent normal tissue, however, was associated with local recurrence (P = 0.025), disease-free interval (P = 0.048), the occurrence of distant metastases (P = 0.019), death (P = 0.049) and disease-free survival (P = 0.048). Volume ratios of DCIS in normal and invasive tissue were not related to known prognostic factors including lymph node stage, grade, tumour size, vascular invasion or patient age. CONCLUSION: There is a significant prognostic effect relating to the extent of DCIS associated with an invasive cancer, particularly with respect to local recurrence of tumour. This effect is restricted to the volume of DCIS in the tissue surrounding the invasive lesion rather than the intratumoral component.

Adult↗
PubMed2001

An audit of "equivocal" (C3) and "suspicious" (C4) categories in fine needle aspiration cytology of the breast.

We have audited the frequency of use and outcome of the "equivocal/atypia probably benign" (C3) and "suspicious of malignancy" (C4) category for breast cytology in our Unit. A total of 14 935 cytological specimens were reported by at least one of the three pathologists with a special interest in breast pathology, according to five categories of the NHSBSP guidelines for cytology reporting, 1992; 3.7% (555 cases) and 3.9% (587 cases) of cases were classified as equivocal (C3) and suspicious (C4), respectively, giving a total rate (C3 + C4) of 7.6%. Of the C3 cases, 68% were subsequently benign and 32% were malignant. Of the C4 cases, 19% were subsequently benign and 81% malignant. The commonest benign lesions in both categories were fibroadenomas (7.6% of C3 and 19.8% of C4), fibrocystic change (14.3% of C3 and 12.5% of C4), radial scars (6.2% of C3 and 10.4% of C4) and papillomas (6.2% of C3 and 6.3% of C4). Of the malignant lesions (particularly those classified as C3), a high proportion were low grade or special type cancers. The categories of atypia probably benign (C3) and suspicious of malignancy (C4) in breast cytology provide a strategy for classification of problematic or uncertain cases; this maintains the predictive value of the benign (C2) and malignant (C5) categories, and allows separation of these difficult cases into clinically useful groups with differing probabilities of malignancy.

Biopsy, Needle↗