PubMed Health⌕ Search

Biomedical subjects

W D Ryder

Publications and source records attributed to W D Ryder.

At least 19 recordsLinked to original sources
PubMed2001

Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides.

OBJECTIVE: Circulating insulin-like growth factor (IGF)-II and IGF binding protein-2 (IGFBP-2) are frequently altered, often in parallel, in numerous pathologies including neoplastic disease but little is known about their normal regulation. This study compared serum IGF-II and IGFBP-2 distributions between acromegalics and a large normal adult population to explore possible determinants. PATIENTS: Sixty acromegalic patients undergoing screening colonoscopy (age range 25-81 years); normative data from 306 healthy adults (age range 20-89 years). MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were measured in healthy adults and acromegalics. Mean growth hormone (GH) levels were obtained for acromegalic patients. Differences were compared using t-tests (unadjusted) and multiple regression models (adjusted for age and gender). Correlations were expressed as Pearson's coefficient (r). RESULTS: For acromegalic patients, GH was significantly correlated with IGF-I (r = 0.50; P < 0.001) and IGFBP-3 (r = 0.29; P = 0.03) but not IGF-II or IGFBP-2. Contrary to expectations, mean IGF-II and IGFBP-2 levels were significantly raised in the acromegalics compared with normals [adjusted mean difference (95% CI) = 226 (181, 271) microg/l and 305 (200, 410) microg/l, respectively]. Ten acromegalic patients had colorectal neoplasia but their presence did not contribute to the elevations in serum IGF-II and IGFBP-2. The (IGF-I + IGF-II)/IGFBP-3 molar ratios were remarkably constant in both healthy adults and acromegalics, but the relationships of the ligands individually with IGFBP-3 were not linear: as IGFBP-3 increased, IGF-I also increased whereas IGF-II initially increased but then decreased. IGFBP-2 did not correlate with IGF-II, but molar concentration significantly correlated with the IGF-II/IGFBP-3 molar ratio (r = 0.40; P = 0.001). CONCLUSIONS: Serum IGF-II and IGFBP-2 levels were paradoxically elevated in acromegalics, independent of the presence of colorectal neoplasia. The (IGF-I + IGF-II)/IGFBP-3 molar ratio appears to be pivotal in determining IGF-II values, which, in turn, expressed as a ratio of IGFBP-3, is related to IGFBP-2. These observations offer new insights into the regulation of these peptides.

Acromegaly↗
PubMed2001

The assessment of irradiated bladder carcinoma using dynamic contrast-enhanced MR imaging.

AIM: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) in distinguishing residual or recurrent tumour from radiation change in patients with bladder carcinoma. MATERIALS AND METHODS: Forty patients with biopsy proven bladder carcinoma were imaged before and at 4 and 12 months after radiotherapy (XRT) using conventional and dynamic contrast-enhanced magnetic resonance imaging at 0.5 Tesla. An enhancement of >1.54 times above baseline at 80 s post-contrast injection proved a reliable indicator of tumour before radiotherapy and was therefore applied to the assessment of patients after XRT. Conventional MR images and dynamic enhancement profiles (DEPs) from the site of previous tumour were scored by three radiologists for the presence of tumour at 4 and 12 months after XRT. Findings were compared with cystoscopic biopsy. RESULTS: Dynamic contrast-enhanced magnetic resonance imaging had negative predictive values of 100% and 93% for tumour recurrence at 4 and 12 months, respectively. The positive predictive values, sensitivity and specificity were 48, 100 and 48% at 4 months and 50, 80 and +76% at 12 months post XRT, respectively. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging may prove reliable in excluding the presence of persistent or recurrent tumour up to 12 months after XRT.

Contrast Media↗
PubMed2001

The relationship between serum GH and serum IGF-I in acromegaly is gender-specific.

In patients with acromegaly, there is a linear association between log10 serum GH and IGF-I. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and in adult GH deficiency, the dose of exogenous GH required to achieve a given serum IGF-I is significantly greater in females than males. We report the influence of gender on the relationship between serum GH and IGF-I in subjects with active acromegaly. A single, fasted, serum sample was obtained from 153 subjects with active disease (87 males; median age, 47.8 yr; range, 20-82 yr) in whom serum IGF-I was at least 30% above the upper limit of an age-related reference range after washout from medical therapy. A linear correlation between serum IGF-I and log10 serum GH was observed (r = 0.53; P < 0.0001), but this relationship was significantly influenced by gender. For a given serum GH value, females were estimated to have serum IGF-I values 82 ng/ml less than males [P < 0.02; 95% confidence interval (CI), 15.2-149]. In females receiving oral E, mean serum IGF-I for a given GH value was 130 ng/ml lower than in males (P = 0.01; 95% CI, 29.8-230.2) but only 60 ng/ml less than the remaining 45 females (NS; P = 0.2). This study demonstrates a gender difference in the relationship between serum GH and IGF-I in patients with active acromegaly consistent with relative GH resistance observed in normal and GHD females, which may, in part, be mediated by E. This observation has important implications for the use of IGF-I as a measure of disease activity.

Acromegaly↗
PubMed2000

Relationship of MRI and clinical staging to outcome in invasive bladder cancer treated by radiotherapy.

AIM: To compare MRI and clinical staging of invasive bladder cancer prospectively and identify additional prognostic features on MRI before radiotherapy. METHODS AND MATERIALS: 143 patients with a pathological diagnosis of transitional cell carcinoma underwent MRI (1.0 T) of the abdomen and pelvis before radical radiotherapy. Tumour size, site, degree of infiltration, presence of adenopathy and hydronephrosis were assessed and an appropriate radiological stage assigned. Following radiotherapy all patients received regular cystoscopic follow-up. Date of first relapse and date of death were recorded. RESULTS: The median follow-up was 2.8 years for survivors. Those patients upstaged from T2a clinically to T3b on MRI had a significantly worse outcome (P = 0.0078). In univariate analysis a number of MRI features were significantly associated with adverse outcome: tumour size, circumferential tumour extent, and presence of hydronephrosis (all P < 0.05). After adjustment for clinical T stage and histological grade, all these MRI features and the MRI T stage were found to confer additional prognostic information in predicting early disease relapse and death (P < 0.05). CONCLUSION: This study demonstrates that MRI before radiotherapy provides valuable additional prognostic information compared to clinical staging.

Aged↗
PubMed2000

Requirement for expert histopathological assessment of ovarian cancer and borderline tumors.

The distinction between borderline ovarian tumours (BOT) and ovarian carcinoma is made by histopathological assessment. Of 64 patients managed according to institutional BOT protocols, 27 (42%) had been referred with a diagnosis of ovarian carcinoma that was subsequently changed to BOT following histopathological review. The 70% 6-year event-free survival of the patients with a revised diagnosis was not significantly different from those who were referred with a diagnosis of BOT. This change in diagnosis is important as it avoids the need for chemotherapy for most patients and results in patients receiving appropriate information concerning prognosis. Interestingly, 24 patients (38.1%) reported a family history of epithelial cancer, a finding that has not been reported previously. Campaign

Adult↗
PubMed2000

Changes in lipoprotein(a) levels measured by six kit methods during growth hormone treatment of growth hormone-deficient adults.

Lipoprotein(a) [Lp(a)], an independent risk factor for cardiovascular disease, has previously been reported to increase, decrease or show no change in growth hormone (GH)-deficient individuals receiving GH replacement. To assess whether these inconsistencies could be attributed to differences in immunoassay methods, Lp(a) was measured by six commercial kits at 0, 3, 6 and 9 months in nine GH-deficient individuals (median age 68.3 years, six male) during 9 months GH therapy. There was a significant rise in Lp(a) with the INCStar immunoturbidimetric (IT) method and the Mercodia enzyme linked immunosorbent assay (ELISA) (P</=0.05, two-tailed Wilcoxon signed rank test), a non-significant rise with the Pharmacia immuno-radiometric assay and the Biopool ELISA methods (P =0.06), and no change with the Immuno ELISA and WAKO IT kits. There was also considerable variation in the values reported within each individual. These results suggest that the previously reported inconsistencies may in part be due to methodological differences, and that the effect of GH on Lp(a) remains unknown. This study highlights the need for a more common approach to the standardization of Lp(a) methods and the selection of antibodies used in them. Better performing methods may allow a more reliable interpretation of the effects of GH on Lp(a)

Aged↗
PubMed2000

Growth hormone treatment of children with brain tumors and risk of tumor recurrence.

GH is increasingly used for treatment of children and adults. It is mitogenic, however, and there is therefore concern about its safety, especially when used to treat cancer patients who have become GH deficient after cranial radiotherapy. We followed 180 children with brain tumors attending three large hospitals in the United Kingdom and treated with GH during 1965-1996, and 891 children with brain tumors at these hospitals who received radiotherapy but not GH. Thirty-five first recurrences occurred in the GH-treated children and 434 in the untreated children. The relative risk of first recurrence in GH-treated compared with untreated patients, adjusted for potentially confounding prognostic variables, was decreased (0. 6; 95% confidence interval, 0.4-0.9) as was the relative risk of mortality (0.5; 95% confidence interval, 0.3-0.8). There was no significant trend in relative risk of recurrence with cumulative time for which GH treatment had been given or with time elapsed since this treatment started. The relative risk of mortality increased significantly with time since first GH treatment. The results, based on much larger numbers than previous studies, suggest that GH does not increase the risk of recurrence of childhood brain tumors, although the rising trend in mortality relative risks with longer follow-up indicates the need for continued surveillance.

Adolescent↗
PubMed1999

Treatment outcome and prognostic factors for relapse after high-dose chemotherapy and peripheral blood stem cell rescue for patients with poor risk high grade non-Hodgkin's lymphoma.

The aim of the study was to determine treatment outcome and identify a particularly high risk group in a consecutive series of 66 patients with poor prognosis high grade lymphoma (NHL) treated with conventional induction chemotherapy followed by high-dose chemotherapy (HDCT) and peripheral blood stem cells (PBSC) rescue. Fifty-one patients with intermediate grade NHL (Kiel) and two or three adverse prognostic features as defined by the age-adjusted International Prognostic Index (IPI) received induction treatment with 7 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone and methotrexate (VAPEC-B) followed by three cycles of ifosfamide/cytarabine. Fifteen patients with high grade Burkitt's and lymphoblastic NHL received 11 weeks of VAPEC-B followed by three cycles of high-dose methotrexate. HDCT for all 66 patients consisted of busulphan/cyclophosphamide followed by autologous PBSC rescue. Thirty-one patients (47%) received HDCT in first complete remission (CR/CRu) and 34 patients (52%) in first partial remission (PR) after conventional chemotherapy. Following HDCT, 42 patients (64%) were in CR/CRu, 19 patients (29%) in PR and one patient had progressive disease. There were four toxic deaths. After a median follow-up period of 27 months (range 7-73) in 46 surviving patients, the actuarial 3-year estimates of overall survival, event-free survival (EFS) and freedom from progression (FFP) were 67%, 65% and 70%, respectively. In univariate analysis, prognostic factors associated with reduced EFS were mediastinal bulk (P = 0.02), > or = 3 extra-nodal sites (P = 0.02), remission status prior to HDCT (P = 0.05), low albumin (P = 0.08) and raised ESR (P = 0.09). No significant difference was observed between patients with intermediate or high grade NHL or between patients with two or three adverse IPI features. Multivariate analysis identified mediastinal bulk (P = 0.01), > or = 3 extra-nodal sites (P = 0.01) and low albumin (P = 0.03) as joint predictors of poor EFS. Remission status prior to HDCT was not found to be significantly associated with reduced EFS, FFP or survival, suggesting early introduction of HDCT may benefit patients with a PR. Based on these three adverse features, three groups (0, 1 or > or = 2 features) could be identified with differing EFS, survival and freedom from progression (FFP) rates at 3 years; 85%, 63% and 20%, respectively for EFS, 84%, 64% and 25% for survival and 85%, 66% and 33%, respectively for FFP. This prognostic model may identify patients with a particularly poor prognosis despite HDCT, who may benefit from other therapeutic approaches.

Adolescent↗
PubMed1999

Content of long-term culture-initiating cells, clonogenic progenitors and CD34 cells in apheresis harvests of normal donors for allogeneic transplantation, and in patients with acute myeloid leukaemia or multiple myeloma.

Using a limiting dilution assay the frequency of long-term culture-initiating cells (LTC-IC) in the apheresis products following mobilization by granulocyte-colony stimulating factor (G-CSP) with or without chemotherapy from 14 normal donors (ND) for allogeneic bone marrow transplantation, 16 patients with multiple myeloma (MM) and 15 patients with acute myeloid leukaemia (AML), where the aphereses were intended for autologous transplantation, were compared. The estimated median incidences of LTC-IC in the first apheresis products from ND, MM and AML were 1/3289, 1/1775 and 1/13075 mononuclear cells (MNC) respectively. The patients with AML had a significantly lower incidence compared with the other two groups (P < 0.0001). There was a positive correlation between the incidence of LTC-IC and the number of CD34+ cells, the number of GM-CFC, and the number of BFU-E. The positive association with GM-CFC or BFU-E was weaker. In these experiments the percentage of CD34+ cells was the best predictor for the frequency of LTC-IC in the peripheral blood progenitor cells (PBPC). In eight cases of MM the LTC-IC assay was performed for both the first and second harvest. All cases had a lower LTC-IC frequency in the second harvest compared with the first, an average of 23% (13-42%, 95% confidence interval) and this reduction was statistically significant (P<0 001); CD34+ cells were also lower (P< 0.001).

Acute Disease↗
PubMed1999

Testicular function after cytotoxic chemotherapy: evidence of Leydig cell insufficiency.

PURPOSE: To evaluate testicular function in men after treatment with cytotoxic chemotherapy. PATIENTS AND METHODS: We measured testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in 209 men after treatment with mechlorethamine, vinblastine, procarbazine, and prednisone, hybrid chemotherapy, or high-dose chemotherapy and in 54 healthy age-matched controls. RESULTS: The mean age of the patients was 38 years (range, 19 to 68 years), and all patients had received chemotherapy between 1 and 22 years previously. Patients had significantly higher mean LH (7.9 v 4.1 IU/L; P < .0001) and FSH levels (18.8 v 3.1 IU/L; P < .0001) than controls. There was no significant difference in mean total testosterone level between the patients and controls, but there was a trend toward a lower mean testosterone/SHBG ratio in the patients (0.63 v 0.7; P = .08). Analysis of the hormonal parameters using a model that allowed for the effects of increasing age on testicular function showed evidence of significant recovery of gonadal function in the first 10 years after treatment. Fifty-two percent of patients had LH levels at or above the upper limit of normal, and 32% of patients had increased LH with testosterone levels in the lower half of the normal range, suggesting a degree of Leydig cell impairment. CONCLUSION: In a significant proportion of men, there is good evidence of Leydig cell dysfunction after cytotoxic chemotherapy. The clinical significance of this Leydig cell dysfunction is not clear, but some of these men may benefit from testosterone replacement. Further studies are warranted.

Adult↗
PubMed1999

Assessment and significance of mediastinal bulk in Hodgkin's disease: comparison between computed tomography and chest radiography.

PURPOSE: In Hodgkin's disease (HD), mediastinal bulk is currently defined from chest radiograph (CXR) measurements as a ratio of the maximum transverse mass diameter to the internal thoracic diameter at T5/6 level > or = 0.33. We evaluated how computed tomographic (CT) measurements of bulk correspond to those obtained from the CXR and correlated nodal mass long axis diameter with freedom from progression. METHODS: Ninety-five adult patients who had a CXR thoracic ratio of greater than 0.3 and a CT scan within 28 days of the CXR were included in the study, provided that both investigations were performed before the start of treatment. Measurements of the widest mediastinal diameter and internal thoracic diameter were made on both CXR and CT scan. The thoracic ratio (TR) was calculated for each modality and compared using paired t tests. The longest diameter of the largest individual nodal mass (LIM(CT)) was also measured from the CT and correlated with freedom from progression using Cox regression. RESULTS: There was excellent correlation between CT and CXR for measurement of TR, with TR(CT) greater than TR(CXR) (mean difference of 2%). A TR(CT) of 0. 35 was found to be equivalent to a TR(CXR) of 0.33. No single measurement of nodal size correlated with the current definition of bulk. However LIM(CT) greater than 10 cm did correlate with increased risk of progressive HD (P =.03), even after adjustment for other prognostic variables (chemotherapy regimen and Hasenclever Prognostic Index). CONCLUSION: Excellent correlation was observed between assessment of TR by CXR and CT scan. The longest diameter of the LIM(CT) greater than 10 cm was found to be associated with an increased risk of disease progression.

Adult↗
PubMed1998

Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin's lymphoma: clinical benefits at no extra cost.

In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor (G-CSF, filgrastim) following peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy (HDCT), 23 consecutive patients aged less than 60 years with poor-prognosis, high-grade non-Hodgkin's lymphoma (NHL) were entered into a prospective randomized trial between May 1993 and September 1995. Patients were randomized to receive either PBPC alone (n = 12) or PBPC+G-CSF (n = 11) after HDCT with busulphan and cyclophosphamide. G-CSF (300 microg day[-1]) was given from day +5 until recovery of granulocyte count to greater than 1.0 x 10(9) l(-1) for 2 consecutive days. The mean time to achieve a granulocyte count > 0.5 x 10(9) l(-1) was significantly shorter in the G-CSF arm (9.7 vs 13.2 days; P<0.0001) as was the median duration of hospital stay (12 vs 15 days; P = 0.001). In addition the recovery periods (range 9-12 vs 11-17 days to achieve a count of 1.0 x 10(9) l[-1]) and hospital stays (range 11-14 vs 13-22 days) were significantly less variable in patients receiving G-CSF in whom the values clustered around the median. There were no statistically significant differences between the study arms in terms of days of fever, documented episodes of bacteraemia, antimicrobial drug usage and platelet/red cell transfusion requirements. Taking into account the costs of total occupied-bed days, drugs, growth factor usage and haematological support, the mean expenditure per inpatient stay was pound sterling 6500 (range pound sterling 5465-pound sterling 8101) in the G-CSF group compared with pound sterling 8316 (range pound sterling 5953-pound sterling 15,801) in the group not receiving G-CSF, with an observed mean saving of 1816 per patient (or 22% of the total cost) in the G-CSF group. This study suggests that after HDCT and PBPC rescue, the use of G-CSF leads to more rapid haematological recovery periods and is associated with a more predictable and shorter hospital stay. Furthermore, and despite the additional costs for G-CSF, these clinical benefits are not translated into increased health care expenditure.

Adult↗
PubMed1998

Factors which affect the CFU-GM content of the peripheral blood haemopoietic progenitor cell harvests in patients with acute myeloid leukaemia.

Autologous peripheral blood haemopoietic stem cells (PBSC) were harvested from 30 patients with de novo acute leukaemia, 29 of whom had entered remission following standard chemotherapy. Correlation of CD34+ cells/kg to CFU-GM/kg in the harvests was good (correlation coefficient = 0.72, P < 0.001). We demonstrated significant associations between the CFU-GM content of the harvest and the following: time to platelets >50 x 10(9)/l post final induction course (P < 0.001), days to harvest from day 1 of intensification/mobilization (correlation coefficient = -0.73, P < 0.001), platelets >20 x 10(9)/l at time of harvest (P = 0.02), time to WBC >1.0 x 10(9)/l post intensification/mobilization (correlation coefficient = -0.70, P < 0.001), and WBC on day of harvest (correlation coefficient = 0.60, P < 0.001). In contrast, we found no relationship between the CFU-GM content of the harvest and patient age up to 65 years, presence of absence of coexistent features of trilineage myelodysplasia at diagnosis, number of induction courses to remission or total number of courses of chemotherapy prior to intensification/mobilization. Haemopoietic recovery after reinfusion of PBSC was highly correlated to the number of CFU-GM infused (neutrophils >0.5 x 10(9)/l rs = -0.72, P = 0.001; platelets >20 x 10(9)/l unsupported rs = -0.71, P = 0.001). Our results show that the number of induction courses received, and thus exposure to cytotoxic agents received, made no significant difference to subsequent CFU-GM harvest content. We collected superior harvests from those patients with faster platelet recovery following mobilization therapy. We also found that faster platelet recovery following the final induction therapy was a better predictor of the CFU-GM harvest following mobilization than was the neutrophil recovery following final induction.

Acute Disease↗
PubMed1997

What is the value of the lateral chest radiograph in the follow-up thoracic lymphoma?

Lateral chest radiography in the investigation of thoracic lymphoma remains a feature of the current literature. This study assessed what information the lateral chest radiograph (CXR) adds in the follow-up of such patients. Eighty-eight patients with known lymphoma who had a CXR and thoracic CT within the same 4-week period were assessed. Five radiologists scored eight mediastinal and hilar nodal groups and eight extramediastinal regions on the frontal CXR as normal, equivocal or definitely abnormal (denoted 0, 1 and 2, respectively). This was repeated 1 week later with a combination of frontal and lateral films. Results were compared with the findings on CT which were scored similarly using accepted criteria for the presence of lymphadenopathy. Where the lateral CXR caused a change in score at any site, this change was compared with CT to determine the effect on diagnostic accuracy. For four of the five observers, the lateral film made no significant difference in diagnostic accuracy in the assessment of mediastinal lymph nodes. A fifth observer derived a small benefit from the addition of the lateral film, although almost 30 % of this was accounted for by changing from a wrong to an equivocal diagnosis. The lateral film did cause a small increase in the detection of pleuro-parenchymal lung lesions, although none of these were clinically significant. We conclude that routine lateral chest radiography is unhelpful in the follow-up of patients with lymphoma.

Adult↗
PubMed1997

Prognostic factors for disease progression in advanced Hodgkin's disease: an analysis of patients aged under 60 years showing no progression in the first 6 months after starting primary chemotherapy.

The aim of this study was to determine whether a very high-risk group based on presenting characteristics could be identified in patients with advanced Hodgkin's disease who may benefit from high-dose chemotherapy (HDCT). Between 1975 and 1992, 453 previously untreated patients aged under 60 years who did not progress in the first 6 months after the start of standard chemotherapy had their hospital notes reviewed. The outcomes analysed were early disease progression (in the 6- to 18-month window following the start of chemotherapy) and disease progression in the whole of the follow-up period. A Cox regression analysis was used to investigate the combined effects of a number of presenting characteristics on these outcomes. Despite the presence of factors with significant effects on the relative rate of progression, the absolute effects in a group identified as having the poorest prognosis were not especially poor. No group could be defined with a freedom from progression rate of less than 70% over 6-18 months, and the worst prognostic group, which included only 53 patients, had an overall freedom from progression rate of 57% at 5 years. Four other reported prognostic indices were evaluated using our data set, but none of the indices was more successful in identifying a very high-risk group. It has not been possible to define a sufficiently high-risk group of patients with Hodgkin's disease based on presenting characteristics for whom HDCT could be advised as part of primary treatment. The search for more discriminating prognostic factors identifying vulnerable patients with a high risk of relapse must continue before a role can be found for HDCT following conventional chemotherapy in patients without disease progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Measurement of long-term culture initiating cells (LTC-ICs) using limiting dilution: comparison of endpoints and stromal support.

Although much progress has been made in defining primitive cell phenotypes using flow cytometry and clonogenic assays, the direct study of marrow repopulating cells remains elusive. Long-term culture initiating cells (LTC-ICs) are arguably the most primitive human hematopoietic cells detectable by in vitro functional assays. Two endpoints have been reported for scoring LTC-ICs in limiting dilution assays. The first endpoint described was the generation of colony forming cells (CFCs) after 5 to 8 weeks of culture. An alternative method for scoring the LTC-IC assay is to identify cobblestone area forming cells. In the present study, estimations of LTC-IC frequency were made by measuring both endpoints and by comparing LTC-IC frequencies measured using limiting dilution assays of normal human bone marrow stroma with the measurements for murine bone marrow stromal cell line M2-10B4. For assays established on normal human bone marrow stroma, there was an equivalence between the two endpoint measures. Likewise, there was an equivalence between the two types of stroma when scoring CFC generation after 5 weeks. However, a consistently higher frequency of LTC-ICs was estimated when scoring cobblestone areas compared with that found when scoring CFC generation on the M2-10B4 stroma (p < 0.0001). Although the murine bone marrow stromal cell line M2-10B4 remains a very useful and consistently reliable alternative to normal human bone marrow stroma, these data indicate that the LTC-IC populations defined by scoring cobblestone areas or by measuring the generation of CFCs on this cell line are, in contrast to those measured using bone marrow stroma, not identical.

Animals↗
PubMed1996

Tumour angiogenesis as a prognostic marker in infiltrating lobular carcinoma of the breast.

The importance of angiogenesis, assessed by tumour microvessel density, as a marker of survival was examined in 160 patients with infiltrating lobular carcinoma of the breast (ILC). The median follow-up was 5.1 years. Of these patients, 46 were node-negative, 59 were node-positive, and in 55 the pathological lymph node status was not known. Tumour sections were immunohistochemically stained with Factor VIII-related antibody. Microvessels were identified using previously recommended methodology and counted in three separate fields, selected from areas of highest vascularity, at x 200 magnification (field area = 0.785 mm2). Only the highest count was considered in the analysis. No association was found between microvessel density and age, menopausal status, tumour size, histological subtype, peritumoural vessel invasion, and lymph node involvement at presentation. There was no association between microvessel density and overall survival or relapse-free survival. These results suggest that microvessel density assessment, using currently recommended methods, is unlikely to be of prognostic value in ILC.

Adult↗