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Biomedical subjects

R E Mansel

Publications and source records attributed to R E Mansel.

At least 91 records · Page 5Linked to original sources
PubMed1996

Inhibition of motility and invasion of human lung cancer cells by invasion inhibiting factor 2.

The motility and invasion of cancer cells are basic requirements for the establishment of distant metastases. In this study, we examined the effect of invasion inhibiting factor 2 (IIF2), a motility/invasion regulatory agent, on the motility, invasion, growth and basement membrane attachment of human lung cancer cells. IIF2 significantly reduced cell dissociation, colony scattering and invasion induced by the motogenic factor, HGF/SF. Western and Northern analyses showed these cells to be positive for the HGF/SF receptor c-met. These effects were blocked by an anti-IIF2 antibody. IIF2 did not affect the growth and attachment of lung cancer cells to the basement membrane. It is concluded therefore that invasion inhibiting factor 2 is an inhibitor of human lung cancer cell motility and invasion in vitro and this may bear some importance in the construction of anti-metastatic therapies.

Angiogenesis Inducing Agents↗
PubMed1996

A critical appraisal of six modern classifications of ductal carcinoma in situ of the breast (DCIS): correlation with grade of associated invasive carcinoma.

The in-situ component of 180 cases of screen detected infiltrating duct carcinoma of the breast was classified according to six published classifications for ductal carcinoma in situ based on architecture, necrosis and cytology. All cases were assessed independently by two experienced observers to assess inter-observer variation. The differentiation of ductal carcinoma in situ as assessed by all the classification systems correlated with the grade of the associated invasive carcinoma (chi-squared between 50 and 107: P < 0.0001). Disagreements were commonest in the assessment of architecture and least common in the assessment of necrosis. For cytonuclear grade most disagreements (62.2%) involved the distinction between low and intermediate as against 33.9% disagreements for intermediate vs. high. Nuclear grade alone and necrosis alone were correlated with the grade of invasive carcinoma associated with the ductal carcinoma in situ and the Nottingham prognostic index of the patient. The Van Nuys classification of ductal carcinoma in situ is commended because it has a low inter-observer disagreement, is significantly correlated with the grade of the infiltrating carcinoma, uses simple well-defined criteria (with no requirement for percentage estimations), is applicable to small numbers of ducts and, most importantly, appears to correlate with disease-free survival.

Breast Neoplasms↗
PubMed1996

Isolated hyperthermic limb perfusion chemotherapy in Merkel cell tumour: a case report.

Merkel cell carcinoma of the skin is a rare malignant tumour first described in 1972 by Toker. The optimal management of this disease has not been clearly defined, especially that of advanced locoregional disease. Surgery, radiotherapy and chemotherapy have been advocated separately or in combination, with less-than-optimal results. Localized high-dose chemotherapy has never been tried, although it would seem to be the logical step forward.

Aged↗
PubMed1996

The senior SHO rotation in Wales--a basis for BST training.

Between 1969-1992 there was a successful surgical registrar rotation in South Wales (1). This was a three-year rotation comprising two years general surgery, six months trauma and orthopaedics and six months surgical specialty. The rotation was aimed at those doctors who had completed senior house officer (SHO) posts in accident and emergency, 6-12 months general surgery and had already obtained the primary FRCS. However, with the recent recommendations of the Calman Report concerning general surgical training (2) changes to this rotation have become necessary, namely to reduce the number of surgical registrars in order to achieve a balance in numbers entering higher surgical training and to shorten the period of training to seven years with two years Basic Surgical Training (BST) and five years Higher Surgical Training (HST). A modified rotation was therefore designed and implemented in South Wales since July 1992. The previous registrar rotation was shortened to two years instead of three ensuring the pre-requirements for entry into HST and eligibility to sit the second part FRCS. The aim of this study was to assess whether the new senior SHO/BST rotation in South Wales is providing adequate training for our surgical trainees to enter into HST. We present our data as a potential basis for setting up a formal BST rotation.

Attitude of Health Personnel↗
PubMed1995

Induction of tyrosine phosphorylation and translocation of ezrin by hepatocyte growth factor/scatter factor.

Ezrin is a member of the TERM family and is a key protein in cytoplasmic membrane-cytoskeleton interactions. This study showed that hepatocyte growth factor/scatter factor (HGF/SF), a cytokine known to regulate motility, morphogenesis and growth of cells, stimulated the tyrosine phosphorylation of ezrin in a human colon epithelial cell line, HT115. After HGF/SF stimulation, ezrin translocated from the cytosol and generalised membrane to the areas of ruffled membrane as visualised by indirect immunofluorescent and immunogold electron microscopy. This effect was inhibited by genistein, a tyrosine kinase inhibitor. It is concluded that HGF/SF induces ezrin translocation by stimulation of its tyrosine phosphorylation and that this plays a key role in HGF/SF induced membrane ruffling.

Actins↗
PubMed1995

Regulation of the expression of E-cadherin on human cancer cells by gamma-linolenic acid (GLA).

E-cadherin is a cell to cell adhesion molecule which acts as a suppressor of metastasis. This study examined the effect of gamma-linolenic acid (GLA), a n-6 polyunsaturated fatty acid, on the expression of E-cadherin in human cancer cells. Western blotting studies demonstrated that treatment of cells with GLA for 24 h increased the expression of E-cadherin in lung, colon, breast, melanoma, and liver cancer cells, but not in endothelial cells and fibroblasts. The results were confirmed by immunocytochemistry. In contrast, two other n-6 fatty acids, linoleic acid and arachidonic acid, failed to induce these changes. The increased expression of E-cadherin was correlated with reduced in vitro invasion and increased aggregation, indicating that the increased E-cadherin expression induced by GLA was biologically active. These data add GLA to the short list of E-cadherin up-regulatory factors. The up-regulation of E-cadherin expression in human cancer cells may contribute to the anticancer properties of GLA.

Antineoplastic Agents↗
PubMed1995

Breast disease.

Explore the source record for details and available documents.

Drainage↗
PubMed1995

Blood flow in breast cancer and fibroadenoma estimated by colour Doppler ultrasonography.

Blood flow was measured by colour Doppler ultrasonography in 33 fibroadenomas of size 5-31 mm and 28 malignant breast masses of 8-37 mm visible on ultrasonography. There was detectable blood flow in 11 fibroadenomas and 21 cancers (P < 0.01). The median peak systolic frequency was 1.0 (range 0.25-2.0) kHz in malignant tumours and 0.5 (range 0.2-1.25) kHz in fibroadenomas. Blood flow was not detected in the eight fibroadenomas of less than 13 mm but was present in five of seven cancers smaller than this. Five of six carcinomas with three or more detectable vessels were classified as grade III on histological examination, compared with two of 11 carcinomas with one or two vessels. Similarly, five of seven cancers with three or more detectable vessels had axillary lymph node metastases compared with two of 13 with only one or two vessels. Detectable blood flow in breast masses is more common in cancer than in fibroadenoma and is highly suggestive of malignancy if the mass is less than 13 mm in size. Malignant tumours with a larger number of vessels are more likely to be of high grade and to have associated axillary node metastases.

Adolescent↗
PubMed1995

Molecular evolution and secondary structural conservation in the B-cell lymphoma leukemia 2 (bcl-2) family of proto-oncogene products.

The nature of the bcl-2 family of proto-oncogenes was analyzed by sequence alignment, secondary structure prediction, and phylogenetic techniques. Phylogenies were inferred from both the nucleic acid and amino acid sequences of the human, murine, rat, and chicken sequences for BCL-2 and BCL-X, human MCL1, murine A1, the nematode Caenorhabditis elegans and Caenorhabditis briggsiae ced-9 proteins, and the sequences BHRF1 from Epstein-Barr and LMW5-HL from African swine fever viruses. Both sequence alignment and secondary structure prediction techniques supported the conservation of both the overall secondary structure and the carboxy-terminal transmembrane domain in all members of the family. All the treeing methods employed (distance matrix, maximum likelihood, and parsimony) supported a tree in which the proapoptotic proteins BCL-2 and BCL-X represent the most recent additions to the group. All the trees also indicated that the viral proteins BHRF1 and LMW-HL arose from a common ancestor, an ancestor they shared in common with the pro-apoptotic control protein BAX, indicating that this function of BAX evolved only recently. The most ancient branches are represented by the nematode ced-9 protein and by the control genes MCL1 and A1, which in the treeing methods employed represent separate lineages within the most ancient grouping. These results demonstrate the evolution of a highly conserved family of developmental control genes from nematode to man--genes that encode proteins essential for normal development but which are highly conserved in terms of predicted structure and possible cellular localization. The evolutionary analysis also indicates that the family may be even larger than originally predicted and that other members are waiting to be discovered.

Amino Acid Sequence↗
PubMed1995

The satisfaction and savings of early discharge with drain in situ following axillary lymphadenectomy in the treatment of breast cancer.

A pilot study was performed to determine if early discharge with the drain in situ following axillary lymphadenectomy is feasible and safe. One hundred and one women who had axillary lymphadenectomy as part of their breast cancer treatment were studied. Ninety-six were offered early discharge with the axillary drain in situ, five were unsuitable for early discharge. The cohort who opted for early discharge (n = 39) had a lower rate of seroma formation (18% vs 34%) and a reduction in median hospital stay of 5 days. Patient satisfaction was high in both groups and there were no complications associated with early discharge or drain displacement. Early discharge after axillary lymphadenectomy with the axillary drain in situ is safe, feasible, popular with patients and offers considerable resource savings.

Adult↗
PubMed1995

Can preoperative factors predict for residual malignancy after breast biopsy for invasive cancer?

The presence of malignancy at the resection margins of a malignant breast biopsy requires difficult therapeutic decisions about whether a re-excision biopsy is necessary. The aim of this study was to determine the factors predisposing to the involvement of the resection margins in 280 women undergoing breast biopsy for invasive malignancy from a single breast screening practice. Resection margins were assessed independently by a single pathologist who noted either the presence of tumour at the margins of the biopsy specimen or in the shavings taken from the biopsy cavity. Resection margin involvement (RMI) occurred in 113 patients. Mammographic microcalcification (MM) was seen in 87 women with invasive cancer and RMI occurred in 53 (61%) compared with 60/193 invasive cancers without MM (P < 0.001). If RMI was present the patients underwent a second procedure to ensure complete tumour excision, and 68% of re-excision specimens from tumours with MM and 36% of tumours without MM contained residual malignancy (P < 0.005). Statistical analysis demonstrated that these observations were independent of tumour size, grade, type, and axillary node status. The presence of mammographic microcalcification therefore indicates that wider than usual surgical resection margins should be taken.

Biopsy↗
PubMed1995

The effect of danazol on discrete benign breast lumps.

Surgical biopsy of benign breast lumps produces a significant surgical workload, morbidity and cost. A double-blind placebo-controlled trial of danazol 200 mg daily was carried out with the aim of reducing the size of solid discrete breast lumps, thereby avoiding surgical biopsy in benign cases. Twenty-two women with lumps diagnosed as benign by clinical examination, mammography and cytology were randomized to take danazol and 26 placebo. The patients were assessed monthly by two clinicians until surgical biopsy. Twenty patients in each treatment group were evaluated and five patients discontinued treatment (two on danazol, three on placebo) and three (all on placebo) were found to be malignant. There was no difference in the number of lumps which responded to treatment with danazol or placebo. There was a reduction in the number of lumps which subsequently developed in the breasts treated with danazol during the 12-month follow-up period, but this failed to achieve statistical significance. Danazol does not promote resolution of solid discrete benign breast lumps. Careful selection of women over 25 years for surgery with solid discrete breast lumps is required, utilizing a dedicated breast cytologist with a multidisciplinary approach, to avoid missing breast cancers.

Adult↗
PubMed1994

Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer.

We have conducted a clinical trial of a novel pure antiestrogen, 7 alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5,(1 0)-triene-3,17 beta-diol (ICI 182780), to assess its tolerance, pharmacokinetics, and short term biological effects in women with primary breast cancer. Fifty-six patients were randomized to either a control group (n = 19), in which they received no preoperative treatment, or a treatment group (n = 37), in which they received daily i.m. injections of ICI 182780 at doses of 6 mg (n = 21) or 18 mg (n = 16) for 7 days prior to primary breast surgery. Serum drug concentrations, gonadotropin levels, and sex hormone-binding globulin levels were measured during the study period by radioimmunoassay. Expression of estrogen receptors (ER), progesterone receptors, the estrogen-induced protein pS2, and the cell proliferation-related antigen Ki67 was determined immunocytochemically in pre- and poststudy tumor samples. Treatment with ICI 182780 caused no serious drug-related adverse events and had no effect on serum gonadotropin or sex hormone-binding globulin levels. Minor adverse events occurred in 5 patients receiving the 6-mg dose and 3 patients receiving the 18-mg dose. The serum concentration of ICI 182780 was dose dependent but showed variation between individuals. There was evidence of an approximately 3-fold drug accumulation over the short treatment period but steady state levels were not reached by the end of the 7 days. In patients with ER-positive tumors, treatment with ICI 182780 was associated with significant reductions in the tumor expression of ER (median ER index, 0.72 before versus 0.02 after treatment; P < 0.001), progesterone receptor (median progesterone receptor index, 0.50 before versus 0.01 after treatment; P < 0.05), and Ki67 (median Ki67 labeling index, 3.2 before versus 1.1 after treatment; P < 0.05). Treatment with ICI 182780 also resulted in a significant reduction in pS2 expression (P < 0.05) but this appeared unrelated to tumor ER status. In conclusion, ICI 182780 was well tolerated after short term administration and produced demonstrable antiestrogenic effects in human breast tumors in vivo, without showing evidence of agonist activity. These properties identify ICI 182780 as a candidate agent with which to evaluate whether a pure estrogen antagonist offers any additional benefit in the treatment of human breast cancer over conventional nonsteroidal antiestrogens, typified by tamoxifen, which exhibit variable degrees of agonist activity.

Aged↗
PubMed1994

Effects of 4-hydroxytamoxifen and a novel pure antioestrogen (ICI 182780) on the clonogenic growth of human breast cancer cells in vitro.

We have investigated the effects on breast cancer cell growth of 4-hydroxytamoxifen (4OHT), a conventional antioestrogen with agonist activity, and 7 alpha-[9-(4,4,5,5,5-pentafluoropentylsulphinyl)nonyl]oestra- 1,3,5,(10)- triene-3,17 beta-diol (ICI 182780), a novel, pure antioestrogen, using established human breast cancer cell lines and cancer cells obtained directly from breast cancer patients with malignant pleural effusions who had relapsed on tamoxifen. The effects of the two agents were assessed using the Courtenay-Mills clonogenic assay, which measures the growth of single cancer cells as colonies suspended in soft agar. The standard assay was modified by the use of defined serum- and phenol red-free growth medium. The growth of oestrogen receptor (ER)-positive MCF-7 cells in the assay was oestrogen responsive. Both antioestrogens inhibited the stimulatory effects of 1 nM oestradiol, but ICI 182780 caused significantly greater inhibition than 4OHT at 0.1-1.0 microM concentrations. In the absence of oestradiol, 4OHT but not ICI 182780 caused significant stimulation of colony formation at low (0.01-1.00 nM) concentrations. Neither antioestrogen had any effects on colony formation by the ER-negative Hs578T cell line. Successful colony formation was obtained in primary cultures from six out of eight malignant effusions. Colony formation was significantly stimulated by 0.1 nM oestradiol in four cases and by 10 nM 40HT in two cases. In contrast, ICI 182780 exhibited no intrinsic stimulatory activity and significantly inhibited both oestradiol- and 4OHT-stimulated cell growth. We conclude that the agonist activity of 4OHT and other conventional antioestrogens may cause treatment failure in some patients by stimulating breast cancer cell growth. The new, pure antioestrogen ICI 182780 is a more potent oestrogen antagonist than 4OHT and exhibits no growth-stimulatory activity. This agent may therefore offer therapeutic advantages over conventional antioestrogens in patients with advanced breast cancer and may be effective after conventional agents have failed.

Adult↗