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Biomedical subjects

C J Gallagher

Publications and source records attributed to C J Gallagher.

At least 37 records · Page 2Linked to original sources
PubMed1995

Intermittent endocrine therapy and its potential for chemoprevention of prostate cancer.

This chapter has reviewed the limitations of the use of chemotherapy in patients with hormone resistant prostate cancer. Although demonstrating that there is a small number of patients with very chemosensitive tumours, the age profile and intolerance to chemotherapy make it highly unlikely that this modality of treatment will be used more routinely despite the increasing evidence that the slow decline of prostate specific antigen with endocrine treatment can be used early to select patients who might respond to chemotherapy. Equally certain is that it will not be of use for chemoprevention of the early stages of this disease. Although some data suggest that tumours that respond rapidly and completely to endocrine therapy may benefit from the use of non-specific immunotherapy, there is no evidence that any form of vaccination therapy would be of value in preventing the disease in the main because all attempts to find evidence of a virus, particularly a human papillomavirus subtype, involved in its aetiology have proved negative. The discovery that standard endocrine therapy induces thymic regeneration and peripheral blood lymphocytosis, taken together with the demonstration that surgical trauma induced by a needle biopsy could accelerate tumour dissemination because of tumour activation by trauma induced release of tissue repair cytokines, has led to the proposal that short term endocrine treatment should be given to all prostate specific antigen positive patients prior to needle biopsy. New information on the slow kinetics of prostate cancer growth, with cancers detected by screening being found up to 20 years before clinical presentation and more than 80% of early tumours failing to double the prostate specific antigen level within 2 years, has led to proposals for a new strategy for endocrine chemoprevention of prostate cancer. This has in part been encouraged by greater confidence in the use of intermittent hormone therapy to treat patients with metastatic disease. These observations have led to the suggestion that it might be possible to prevent deaths by treating early cases detected from prostate specific antigen screening with short term (1-3 months) endocrine treatment every 5 to 10 years.

Androgen Antagonists↗
PubMed1994

Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium.

In order to examine the production of marker proteins, a reproducible method has been established for culturing purified epithelial cells from normal and malignant endometrium. We have examined the differential expression of secretory proteins using immunohistochemistry in frozen tissue sections, immunocytochemistry in cell cultures derived from the same specimens and protein assays on the culture supernatants. Placental protein 14 (PP14) was produced by normal premenopausal epithelium but not by the post-menopausal or malignant endometrial epithelium. In contrast, placental alkaline phosphatase (PLAP) was produced by endometrial cancers and the endometrial adenocarcinoma-derived cell line Ishikawa, but not by the normal endometrial epithelium. Other markers such as CA-125, which was produced by both normal and malignant endometrium but not by the cell line, and human chorionic gonadotrophin (beta-hCG), which was produced by Ishikawa cells but not by any of the fresh tissues, were less cancer specific. Placental alkaline phosphatase is a direct product of endometrial cancers that can be readily assayed in serum using this two-site assay to test its clinical usefulness in monitoring patients at risk for endometrial cancer.

Adenocarcinoma↗
PubMed1994

Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease.

This phase II study evaluates the efficacy and toxicity of a prolonged schedule of oral etoposide in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Forty-seven patients participated, 20 of whom had received more than one prior treatment. Seventy-seven per cent had evidence of disease progression during or within 6 months of the previous chemotherapy. Initially, oral etoposide, 50 mg b.d. (regardless of patient size), was given for 14 days on a 21-day cycle. However, after encountering toxicity, the schedule was modified to 7 days' treatment escalating to 10 then 14 days if well tolerated. Among 41 assessable patients there were two complete and eight partial objective responses (24% response rate; 95% confidence interval 12-41%). Nine further patients (22%) had stable disease, four with a sustained fall of > 50% in CA-125. Median duration of response or stable disease was 35 weeks (range 21-49). Overall median survival was 41 weeks from study entry (range 2 to 96+ weeks). Toxicity for most patients was mild, but sporadic severe myelotoxicity occurred, with two treatment-related deaths. Risk factors for severe toxicity were: performance status 3; hepatic impairment; renal impairment. We conclude that oral etoposide has activity in platinum-resistant ovarian cancer and that it is a useful palliative therapy. It has significant toxicity which may be avoided by appropriate patient selection and an escalating-duration schedule.

Administration, Oral↗
PubMed1993

Combination chemotherapy for intermediate and high grade non-Hodgkin's lymphoma.

One hundred and eighteen consecutive adults with newly diagnosed intermediate and high-grade non-Hodgkin's lymphoma were treated with chemotherapy comprising Doxorubicin, Cyclophosphamide, Vincristine and Prednisolone with mid-cycle Methotrexate (MTX) and leucovorin rescue ('CHOP-M'). Intrathecal MTX was given with each treatment cycle as central nervous system (CNS) prophylaxis. 'Clinical remission' was achieved in 70/110 evaluable patients (64%), complete remission: 45/110, (41%), good partial remission: 25/110 (23%). Twenty two patients (19%) died prior to completion of therapy, 18 patients had persistent disease. Hyponatremia (< 137 mmol l-1), advanced age and hypoalbuminaemia (< 32 g l-1) correlated adversely with achievement of CR (P = 0.0007, 0.0005 and 0.04 respectively). With a minimum follow up of 41 years, 47 of the seventy patients (67%) in whom clinical remission was achieved remain well, 19 have developed recurrent disease, resulting in an actuarial projected remission duration of 70% at 8 years. Four died in CR. There has been only one isolated CNS recurrence. On univariate analysis, hypoalbuminaemia, hyponatremia and beta 2 microglobulin (> 3) correlated with unfavourable outcome in terms of duration of remission (P = 0.0009, 0.007 and 0.04 respectively). On multivariate analysis, only the serum sodium (0.002) and advanced age (0.01) were predictive for remission duration. Fifty patients (45%) are alive, the overall actuarial projected survival is thus 42% at 8 years. On univariate analysis, age, hypoalbuminaemia, hyponatraemia, liver involvement and the presence of B symptoms correlated unfavourably with survival. On multivariate analysis, hypoalbuminaemia, advanced age, hyponatraemia, male gender (aged > 50) and diffuse large cell or large cell, immunoblastic histology (Working Formulation) had an adverse effect (P = 0.003, < 0.0001, < 0.0001, 0.002, and 0.03). It was further possible, using cut-off points of 32 g l-1 and 136 mmol l-1 for albumin and sodium respectively to define prognostic categories for patients who differed significantly in terms of survival.

Adolescent↗
PubMed1992

Phase I study comparing continuous infusion of recombinant interleukin-2 by subcutaneous or intravenous administration.

22 cancer patients entered a randomised phase Ib trial comparing the effects of low-dose recombinant interleukin-2 (300 micrograms/m2, approximately equivalent to 6.4 x 10(6) cetus units or 38 x 10(6) U per day) given continuously by intravenous or subcutaneous infusion. At 48 h after two 5-day courses, median lymphocyte levels (x 10(9)/l) were 6.0 (387% increase) in the subcutaneous arm (n = 9) and 5.9 (369% increase) in the intravenous arm (n = 8). Liver and renal toxicity were similar in the two groups. One minor response lasting 4 months occurred in 12 renal cancer/melanoma patients receiving subcutaneous treatment and one durable complete remission continuing at 30 months and one minor response lasting 10 months occurred in 6 renal cancer/melanoma patients receiving intravenous treatment.

Adult↗
PubMed1992

Pilot study to evaluate impact of a policy of adjuvant chemotherapy for high risk stage 1 malignant teratoma on overall relapse rate of stage 1 cancer patients.

A total of 41 patients with stage 1 malignant teratoma of the testis treated from January 1986 to June 1990 was entered into a pilot study of 2 courses of adjuvant cisplatin-based combination chemotherapy. Of the patients 22 had a high or intermediate risk of relapse according to the Medical Research Council (United Kingdom) prognostic factor analysis and surveillance was instituted for 19 patients with a low relapse risk. The overall relapse rate in this group of patients (median followup 2 years) was 9.7% (5% in the adjuvant group and 16% in the surveillance group), which was significantly better than the 35% rate in the historical series treated by surveillance from 1980 to 1985 and equaled or was possibly better than that reported from adjuvant retroperitoneal lymph node dissection. Justification for consideration of 1 course of adjuvant treatment for such cases is reviewed, and the need for examination of such an approach in a neoadjuvant setting with either lymph node dissection or surveillance is examined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A new treatment for endometrial cancer with gonadotrophin releasing-hormone analogue.

OBJECTIVE: To test the antitumour effect of gonadotrophin releasing-hormone (GnRH) analogues in women with recurrent endometrial cancer. DESIGN: An open phase II observational trial of GnRH analogues. Serial measurements of gonadotrophins, sex hormones and tumour dimensions were made together with repeat biopsy when possible to assess the response to treatment. SETTING: The outpatient clinics of the Department of Medical Oncology at The Royal London, Royal Marsden and St Bartholomew's hospitals. SUBJECTS: 17 patients with endometrial cancer which had recurred after surgery, radiotherapy and progesterone treatment and was symptomatic, progressive and assessable for response. INTERVENTION: Monthly subcutaneous injection of GnRH analogue. MAIN OUTCOME MEASURES: Reduction in serum gonadotrophins and reduction in tumour dimensions. RESULTS: Six out of 17 patients (35%, 95% CI 12.6-58%) achieved a complete or partial remission which continues for a median of 20 months with no adverse effects. CONCLUSION: GnRH analogues have a significant antitumour effect in recurrent endometrial cancer which warrants further examination in comparison with progestogens.

Adenocarcinoma↗
PubMed1990

Increased whole blood viscosity during coronary artery bypass surgery. Studies to evaluate the effects of soluble fibrin and poloxamer 188.

This study was designed to test the hypothesis that soluble fibrin complexes resulting from the trauma of surgery could produce elevated blood viscosity, to characterize the soluble fibrin polymers, and to evaluate in vitro the effect of a new hemorheologic agent, poloxamer 188, on viscosity in these abnormal situations. Ten patients undergoing aortocoronary bypass surgery were studied before and at various times after surgery. By 6 h after surgery, the mean hematocrit decreased by 23%, fibrinogen decreased 48%, and erythrocyte sedimentation rate decreased 33%, whole blood viscosity at a low shear rate rose on average of 69% and soluble fibrin rose 118%. Over the 6-day observation period, the concentrations of soluble fibrin paralleled the changes in viscosity, whereas the concentrations of fibrinogen varied nearly inversely with viscosity. The effects of various forms of fibrinogen and fibrin were tested by additions to normal blood. Soluble fibrin polymers, but not fibrin monomers, increased blood viscosity two to three fold. Poloxamer 188 reduced the viscosity of all patient samples to the normal range. These data support the hypothesis that increased whole blood viscosity at low shear rates is caused by hydrophobic adhesion of fibrin polymers to red cells and that poloxamer 188 normalizes viscosity by effectively disrupting the weak hydrophobic bonds.

Biopolymers↗
PubMed1989

A dose escalation study of carboplatin and ifosfamide in advanced ovarian cancer.

A dose escalation study of carboplatin (CBDCA) and ifosfamide was carried out in 35 patients with advanced ovarian carcinoma to determine the toxicity and therapeutic effect of this combination. In all, 13 patients had recurrent ovarian carcinoma, 11 had abdominal carcinomatosis of probable ovarian origin and 9 had newly diagnosed stage III/IV ovarian cancer. Myelosuppression was the major dose-limiting toxicity. At a dose of 400 mg/m2 CBDCA plus 5,000 mg/m2 ifosfamide, 61% of courses were associated with grade 3 leukopenia and 27%, with grade 3 thrombocytopenia. The lowest leukocyte and platelet counts occurred at a median of 14 days after treatment and cytopenia persisted for a median of 8 days. Myelotoxicity was cumulative with successive courses at this dose level, whereas at a dose of 400 mg/m2 CBDCA plus 4,000 mg/m2 ifosfamide it was possible to deliver the planned six courses of treatment. No other untoward toxicities were observed. A clinical response was achieved in 16/33 patients (49%), with 10 complete remissions (CRs), of which 3 were pathologically confirmed at laparotomy. No significant dose-response relationship was demonstrated in this heterogeneous group of patients. The predicted median duration of response is 12 months. CBDCA plus ifosfamide is an active combination therapy for ovarian cancer that merits further comparison with CBDCA alone. The recommended doses for six courses are 400 mg/m2 CBDCA plus 4,000 mg/m2 ifosfamide.

Antineoplastic Agents↗
PubMed1989

Incidence of Cell-Saver contamination during cardiopulmonary bypass.

During regular bacteriological surveillance of cardiac surgical equipment and patients, the Cell Saver apparatus (CSA) was prospectively evaluated to determine if it represented an additional risk for infection. Nineteen patients were studied. After each operation, the effluent from the CSA was sterilely sealed for subsequent culture. A total of 42 aerobic and 42 anaerobic cultures were made. Postoperatively all patients were evaluated daily for four days and before discharge for clinical evidence of infection. Four patients had positive CSA cultures without evidence of postoperative clinical infection. Five patients in whom postoperative infectious complications developed had negative CSA cultures. Ten patients had negative CSA cultures and no evidence of postoperative infection. We conclude that the CSA does not appear to contribute to the risk of infection in cardiac surgical patients and that it is a safe adjunct to cardiac surgery.

Adult↗
PubMed1987

High dose versus low dose medroxyprogesterone acetate: a randomized trial in advanced breast cancer.

One hundred and twenty-four patients with advanced breast cancer were randomly allocated to treatment with either low dose (300 mg/day) or high dose (1000 mg/day) oral medroxyprogesterone acetate. The objective response rate was 24% for both treatment groups. For premenopausal patients, responses were achieved in two out of four on low dose and three out of six on high dose therapy (overall 5 out of 10 responders). No significant differences in response were seen in relation to previous endocrine therapy or site of disease. Both treatments were associated with a high incidence of bone pain relief (43 and 52%) but a low objective response rate (13%) in bone. Median response duration (10 vs. 11 months) and survival (13 vs. 11 months) were not significantly different for the two treatments. Both treatments were in general well tolerated, but toxicity was greater with the high dose treatment. Low dose oral medroxyprogesterone acetate is as effective as high dose therapy in the treatment of advanced breast cancer, and is cheaper and less toxic.

Adult↗
PubMed1987

Follicular non-Hodgkin's lymphoma.

FL is usually widely disseminated at presentation and responds to radiotherapy, single agent chemotherapy and combination therapy. The disease pursues a remitting and relapsing course with continuing sensitivity to brief periods of treatment until a terminal phase of drug resistance, transformation, or bone marrow failure is reached. Newly recognized prognostic factors indicative of tumour bulk include hepatosplenomegaly, B symptoms, anaemia and abnormal liver function. Using these factors it is possible to identify those patients at first diagnosis for whom conservative management is appropriate and those with a much less favourable prognosis for whom experimental treatments are being investigated.

Humans↗
PubMed1986

Follicular lymphoma: prognostic factors for response and survival.

One hundred forty-eight patients with newly diagnosed follicular lymphoma were treated over a 12-year period. Twenty-two patients received radiotherapy for stage I and II disease, followed by adjuvant chemotherapy in 14 patients. One hundred thirteen were treated at presentation with short courses of chemotherapy, most often with single-agent chlorambucil for bulky stage II and stages III and IV disease. Thirteen patients were managed expectantly until there was evidence of disease progression. The median survival was 9 years. Patients treated with radiotherapy for stage I and II disease had an 83% relapse-free survival, but those with bulky stage II or stages III and IV disease treated with chemotherapy pursued a remitting and relapsing course with a 70% response rate at initial and subsequent retreatments, but a median duration of remission of 4 years in stage III and 1 year in stage IV disease (P = .041). Patients were observed in relapse and retreatment was administered as appropriate, once every 33 months on average. Poor prognosis patients could be identified by a combination of the presentation characteristics: B symptoms, hepatosplenomegaly, anemia, and abnormal liver function. These factors predicted a poor response to treatment and correlated with a short survival. Histologic subgroups were not associated with differences in survival, but transformation to a diffuse high-grade lymphoma was observed in 23 of the 72 patients (32%) at risk, with a median follow-up of 6 years and 6 months, and was associated with a very poor prognosis. The present treatment strategy has proved successful for most patients with localized disease and those older patients with indolent small volume disseminated follicular lymphoma. New approaches are being investigated for the younger poor prognosis patients.

Adult↗
PubMed1984

Cellular distribution of p68, a new calcium-binding protein from lymphocytes.

A Ca2+-binding protein of mol. wt. 68 000 ( p68 ) is a major component of a Nonidet P-40 insoluble fraction of human and pig lymphocyte plasma membrane. An affinity-purified rabbit antibody has been produced against p68 and used to study its cellular distribution. The antibody stained fixed and permeabilised human B lymphoblastoid cells, peripheral blood lymphocytes and sections of human tonsil. Whole cells, however, were not stained, indicating that the protein was not represented at the cell surface. This assignment was consistent with the detection of p68 in immunoprecipitates from biosynthetically- but not surface-labelled cells. It is concluded that p68 is located on the cytoplasmic face of the plasma membrane. Subcellular fractionation experiments confirmed that p68 was largely membrane-bound in lymphocytes, although a small soluble fraction (approximately 10% of the total) was detected. Sub-fractionation of lymphocyte membranes revealed that p68 was associated not only with the plasma membrane but also with other endomembrane systems. As judged by immunoprecipitation, p68 was present in a variety of cultured cell lines of both lymphoid and non-lymphoid origin. p68 demonstrated a diffuse distribution in fixed and permeabilised fibroblasts which did not correspond to the distribution of either microfilaments or intermediate filaments. However, in detergent-extracted cells the protein was localised in a lamina-like network. A similar immunofluorescent staining pattern has recently been observed for spectrin-related proteins in the detergent-resistant cytoskeleton of fibroblasts. It is suggested that p68 is part of a sub-membranous cytoskeletal complex not only in lymphocytes but also in other cell types.

Animals↗