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Biomedical subjects

A Howell

Publications and source records attributed to A Howell.

At least 235 records · Page 13Linked to original sources
PubMed1986

Molecular expression of epitopes recognized by monoclonal antibodies HMFG-1 and HMFG-2 in human breast cancers: diversity, variability and relationship to prognostic factors.

Epitopes recognised by the monoclonal antibodies HMFG-1 and HMFG-2 are found on glycoprotein components in human breast cancers. This study used immunoblotting techniques to ascertain their molecular diversity, assess their relationship to known prognostic factors, and investigate their expression in sequential samples of breast tumours from individual patients. Both epitopes were expressed on components of a wide variety of molecular weights (HMFG-1, 130 to 450kDa; HMFG-2, 90 to 450kDa). The HMFG-2 epitope was expressed more frequently on components of less than 200kDa (p less than 0.0001). Progesterone receptors (PR), small tumour size and low histological grade correlated significantly with HMFG components greater than or equal to 300kDa. Higher staining intensity was associated with increased likelihood of PR positivity. Paired sequential samples were taken, with a median interval of 8 days, from 38 patients, 23 of whom were administered tamoxifen. In the majority of tumours profiles of expression of components carrying the epitopes were identical in both samples (HMFG-1, 30/38; HMFG-2, 22/38). Overall the results suggested that there was no consistent relationship between the differences observed and tamoxifen administration. We conclude that expression of the HMFG-1 and HMFG-2 epitopes is relatively constant in most tumours, but variable (and possibly subject to modulation) in others, and that their expression, particularly on high molecular weight components, is related to factors associated with good prognosis (PR, small size, low grade), and may be of independent prognostic value.

Antibodies, Monoclonal↗
PubMed1986

Occurrence of a fetal fibroblast phenotype in familial breast cancer.

We have previously shown that fetal and adult human skin fibroblasts display distinctive migratory phenotypes when cultured on 3-dimensional collagen gels in vitro. In the present study, we have used this information to assess the migratory behavior of fibroblasts obtained from patients with either benign or malignant breast disease, and correlated this with the presence of a family history of breast cancer. We have observed that fibroblasts from 17/34 patients with no previous family history of breast cancer displayed fetal-type behavior in our assay system; in contrast, fibroblasts from 15/16 patients with a positive family history of breast cancer behaved abnormally. This apparently increased probability of expressing a fetal-type migratory phenotype in the patients with a family history is statistically significant (p less than 0.008). Skin fibroblasts obtained from 2 healthy and unaffected first-degree relatives (one male and one female) of patients with a family history of breast cancer also exhibited a fetal-type migratory phenotype.

Breast Diseases↗
PubMed1986

A new hormonal therapy for prostatic cancer: long-term clinical and hormonal response.

Twenty-four patients with advanced prostatic cancer were treated with daily injections of the LHRH analogue ICI 118630 (Zoladex) for up to 2 1/2 years. Successful long-term suppression of LH (luteinising hormone) and testosterone was observed without any escape of testosterone. Immunoreactive LH concentrations rose significantly following the daily injection of LHRH analogue but there was no corresponding rise in testosterone concentrations, suggesting altered bioactivity of the LH. A long-term clinical response was obtained in 10 patients (41.6%) and the median duration of response in these patients was 25 months. Eight of the 10 had well to moderately differentiated tumours. The actuarial median survival of all patients was 22 months.

Aged↗
PubMed1986

Testosterone and gonadotrophin profiles in patients on daily or monthly LHRH analogue ICI 118630 (Zoladex) compared with orchiectomy.

Diurnal profiles of circulating gonadotrophins and testosterone have been measured in patients with prostatic carcinoma on long-term treatment with the LHRH agonist analogue ICI 118630, which was administered either by subcutaneous daily injection or monthly injection of the depot preparation. These have been compared with profiles in patients who had undergone orchiectomy. Daily injection of the analogue induced a significant rise in the level of LH but this was not associated with a significant rise in circulating testosterone. There was no diurnal variation of LH or testosterone concentration in patients receiving the depot preparation and this did not differ in patients who were "mid-cycle" compared with those who were "end-cycle". The depot preparation did, however, induce significantly lower circulating levels of testosterone than did daily injection of the analogue and the levels were comparable with those achieved after orchiectomy.

Aged↗
PubMed1986

A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer.

We randomized 122 premenopausal women to receive tamoxifen or to undergo a surgical oophorectomy. Of 54 evaluable women treated with tamoxifen, 24% had an objective response, as compared with 21% of 53 women having an oophorectomy. The median duration of response for tamoxifen (20 months) was longer than that for surgical oophorectomy (7 months), but this did not achieve statistical significance (P = .056). Overall median survival was 15 months for 58 patients receiving tamoxifen and 25 months for 53 patients undergoing oophorectomy (P = .18). Toxicity was greater in those undergoing oophorectomy, though both treatments were well tolerated. In those premenopausal women for whom hormonal therapy is indicated, tamoxifen is a suitable alternative to surgical oophorectomy.

Adult↗
PubMed1986

Intralobular stromal fibroblasts in the resting human mammary gland: ultrastructural properties and intercellular relationships.

The intralobular stroma of the resting human mammary gland was studied by thin-sectioning transmission electron microscopy on tissue obtained from reduction mammoplasty or adjacent to fibroadenomas. The arrangement of delimiting fibroblasts around the epithelium and their possession of contacts as shown by earlier studies were confirmed. Observations on other ultrastructural aspects show these cells to have abundant rough endoplasmic reticulum, a well developed Golgi apparatus and vesicles considered to contain collagen-precursor, and conflict with earlier data. The fine structure of those fibroblasts without close epithelial proximity has been described for the first time and was similar to that of delimiting fibroblasts. Other features applicable to both categories of fibroblast included: variation in overall staining intensity, structures resembling hemi-desmosomes, simple junctions, and close juxtapositions of cell surfaces forming 'contacts' with other fibroblasts as well as with mononuclear cells (lymphocytes, plasma cells, mast cells, macrophages). These cell contacts have not been documented previously. Contacts were structurally undifferentiated, forming spaces 20-50 nm wide which were occluded by lanthanum nitrate. Intralobular stromal cells were therefore organised into a kind of reticulum. The possible functions of this network are discussed. The concept of the epithelial-stromal junction is re-assessed in the light of these observations.

Adolescent↗
PubMed1985

Stereospecificity of 2-methylpiperidine binding to a nicotinic up-regulatory site in the rat brain P2 preparation.

(+/-)-2-Methylpiperidine has a high degree of specificity in enhancing the binding of (-)-[3H]nicotine in the rat brain P2 preparation. (-)- and (+)-2-Methylpiperidine have been resolved. The (+) but not the (-) isomer increased the binding of (-)-[3H]nicotine. The two isomers were equally effective in inhibiting the binding of (-)-[3H]nicotine in high concentrations. These data provide additional support for a stereospecific nicotinic up-regulatory site.

Animals↗
PubMed1985

Preliminary report on use of depot formulation of LHRH analogue ICI 118630 (Zoladex) in patients with prostatic cancer.

A study was conducted of the response of the pituitary-testicular axis to two different methods of administration of the luteinising hormone releasing hormone (LHRH) analogue ICI 118630 (Zoladex) in patients with prostatic cancer. The analogue was given by continuous infusion to four previously untreated patients with prostatic cancer for 60 days (group 1). Subsequently a further four patients were given a depot formulation of the same analogue by subcutaneous injection once every 28 days (group 2). Both methods of administration produced similar, successful suppression of luteinising hormone (LH) associated with a reduction of testosterone to castrate concentrations. The median basal testosterone concentrations before treatment in groups 1 and 2 were 20.6 and 14.1 nmol/l (5.94 and 4.07 ng/ml) respectively; these were reduced to 1.4 and 1.1 nmol/l (0.40 and 0.32 ng/ml) within four weeks of the start of treatment. The median basal LH concentration in groups 1 and 2 were 7.9 and 16.6 IU/1 respectively, which were suppressed to 2.6 and 2.4 IU/1 by four weeks. The suppression of LH and testosterone was maintained with continuous subcutaneous infusion for up to 60 days in group 1, and by subsequent injections of the depot every 28 days in group 2. The use of depot preparation of an LHRH analogue to suppress gonadotrophin and sex hormone secretion offers the convenience of once monthly injections when LHRH analogues are required for the long term treatment of elderly patients with prostatic cancer and children with precocious puberty.

Aged↗
PubMed1985

Retroperitoneal tumour infiltration detected by bone scanning in patients with infiltrating lobular carcinoma of the breast.

Radionuclide bone scans performed in some patients with carcinoma of the breast showed abnormal retention of isotope in the renal pelvis which developed and progressed during the period of follow-up after mastectomy. This phenomenon was seen in 15 of 30 patients with infiltrating carcinoma of the breast (ILC) but in none of 29 with infiltrating duct carcinoma (IDC). Autopsies were performed in eight of the patients with ILC and three of those with IDC. Diffuse retroperitoneal and ureteric infiltration was seen in seven (88 per cent), with ILC and none with IDC. These data suggest that this scan abnormality is an indicator of retroperitoneal spread by ILC.

Bone Neoplasms↗
PubMed1985

Carcinomatous meningitis associated with infiltrating lobular carcinoma of the breast.

The records of 365 patients with advanced carcinoma of the breast were examined to identify those with CNS involvement. Nineteen (5.2%) developed parenchymal cerebral deposits and 10 (2.7%) developed meningeal infiltration during the course of their disease. Parenchymal cerebral deposits were almost exclusively associated with infiltrating duct carcinoma (95%) and meningeal infiltration (carcinomatous meningitis) was almost exclusively associated with infiltrating lobular carcinoma. Meningeal infiltration occurred late in the course of advanced disease and was associated with diffuse involvement of the bone marrow and abdominal structures.

Adult↗
PubMed1985

Activity of JM9 in advanced ovarian cancer: a phase I-II trial.

Thirty-nine patients with advanced solid tumors, including 28 with ovarian cancer, were entered in a phase I-II trial of a new platinum analog, JM9. Twenty-three patients had received prior chemotherapy which did not include cisplatin. Based on preliminary information from an ongoing study, our starting dose was 180 mg/m2. The total dose of JM9 was administered in 1 L of saline infused over 1 hour, with no additional hydration or electrolyte supplementation. Courses were repeated at 3-week intervals or after full recovery from thrombocytopenia. One hundred thirty-nine courses (range, one to six per patient) were administered at four dose levels: 180 mg/m2 (13 courses); 240 mg/m2 (64 courses); 300 mg/m2 (45 courses); and 350 mg/m2 (17 courses). The dose-limiting toxic effect was thrombocytopenia, which was dose-related and cumulative. Median platelet count nadirs were 50, 47, 25, and 28 X 10(9)/L for previously treated patients at dose levels of 180, 240, 300, and 350 mg/m2, respectively. For patients who had not received prior chemotherapy, the corresponding values were 403, 61, 44, and 36 X 10(9)/L. The nadir was predictable at Day 14 with recovery by Day 21 in earlier courses, but with delay of recovery to Days 28-42 in later courses and at higher dose levels. Twenty-five courses of chemotherapy in 15 patients were associated with a platelet count nadir of less than 20 X 10(9)/L, but despite this, serious hemorrhage was rare. Leukopenia was dose-related and mild; the median wbc count (X 10(9)/L) was 2.2 (range, 1.0-7.3) at the highest dose level of 350 mg/m2. The leukocyte count nadir was later than that for the platelet count (Days 21-28), and recovery was often not complete by the time of retreatment. All patients showed a progressive rise in mean corpuscular volume in successive courses, often accompanied by a fall in hemoglobin. Transfusions were required in 14 patients, 12 of whom had received prior chemotherapy. Nausea and vomiting, starting within 1 hour of drug administration, occurred in all patients, but appeared to be less severe and prolonged compared to that occurring with cisplatin. Diarrhea occurred in most patients at the two higher dose levels. There was no evidence of significant renal impairment, electrolyte disturbance, hearing loss, or peripheral neuropathy. Two patients had mild allergic reactions shortly after drug infusion and two others developed vasculitic rashes which were self-limiting.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer.

327 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after total mastectomy and axillary clearance, to receive either no additional treatment or oral cyclophosphamide 80 mg/m2 on days 1-14, intravenous methotrexate 32 mg/m2 on days 1 and 8, and intravenous fluorouracil 480 mg/m2 on days 1 and 8 (CMF), which was repeated every 28 days for twelve cycles. There was a significantly longer relapse-free survival (RFS) in patients treated with CMF. A prolonged RFS was seen in premenopausal patients, those with 1-3 nodes involved, and those with 4 or more nodes involved, but a similar trend in postmenopausal patients failed to reach statistical significance. RFS was greater in patients with CMF-induced amenorrhoea than in controls and in treated patients whose primary tumour contained progesterone receptors. Dose of chemotherapy did not have a significant effect on RFS. Survival was not influenced by treatment.

Adult↗
PubMed1984

Steroid-hormone receptors and survival after first relapse in breast cancer.

Oestrogen receptors were measured in the primary breast tumours of 508 patients and progesterone receptors in those of 486 patients. Survival from mastectomy was significantly longer in patients with receptor-positive tumours. There was no significant difference between patients with receptor-positive and receptor-negative tumours in the relapse-free interval, but survival from first relapse was longer in patients with receptor-positive tumours. Axillary node status and tumour size indicated the probability of relapse but did not influence the length of survival after relapse. Response to tamoxifen or ovarian ablation was known in 65 of the 137 patients who relapsed. Survival from first relapse was significantly longer in patients who both responded to hormone therapy and had receptor-positive tumours. Patients who did not respond to hormone therapy and had receptor-positive tumours had the same survival characteristics as those with receptor-negative tumours who did not respond.

Breast Neoplasms↗
PubMed1984

The prognostic significance of two epithelial membrane antigens expressed by human mammary carcinomas.

As many patients with mammary carcinoma are now treated by conservative forms of surgery, there is a need for prognostic information obtainable from the primary tumour alone. One possible source is the antigenic profile of tumour cells. Using an indirect immunoperoxidase technique, we stained histological sections of the primary tumour from 175 patients with each of two monoclonal antibodies (HMFG-1, HMFG-2), raised against milk fat globule membrane antigens known to be preserved in formalin-fixed tissues. Sections were assessed by light microscopy as to both the overall distribution of antigen expressed and its site in tumour cells. The findings were related to relapse-free survival by life-table analysis. The median duration of follow-up was 36 months. Two patterns of staining with antibody HMFG-1 gave information of prognostic significance but staining with HMFG-2 was without significance. Complete absence of staining with HMFG-1 in 13 patients was associated with an extremely poor prognosis and 10 (77%) of these patients developed metastases within 18 months of follow-up (p less than 0.001). Extracellular staining (ECS) in 22 patients, however, was associated with a favourable prognosis. As assessed by a semi-quantitative method, only one patient (5%) demonstrating a high level of ECS developed metastases (p less than 0,004). These two patterns were analysed for a relationship to other prognostic indicators. Absence of staining was independent of histological grade, tumour size, axillary lymph node status and menopausal status. ECS was associated with low histological grade although this relationship was not absolute. In addition to their use in diagnosis, we conclude that monoclonal antibodies such as HMFG-1 may be useful as prognostic indicators.

Antibodies, Monoclonal↗