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Biomedical subjects

R T Oliver

Publications and source records attributed to R T Oliver.

At least 19 recordsLinked to original sources
PubMed1992

Bleomycin lung: the effect of different chemotherapeutic regimens.

A review of hard-copy computed tomography (CT) images of patients who had undergone chemotherapy for testicular teratoma revealed that the incidence of lung toxicity appeared to be lower in those who had received bleomycin by slow infusion [EBCi (3) regimen, etoposide/bleomycin/cisplatin] rather than by intravenous bolus [PVB regimen, cisplatin/vinblastine/bleomycin; BEP (5) regimen, bleomycin/etoposide/cisplatin]. This difference reached statistical significance only for PVB vs EBCi (3) (t = 2.63, P less than 0.01). Nevertheless, in view of continuing reports of mortality resulting from bleomycin-induced pulmonary fibrosis in patients receiving the drug by i.v. bolus, further exploration of these results is clearly justified.

Antineoplastic Combined Chemotherapy Protocols↗
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

Induction of MHC antigens by tumour cell lines in response to interferons.

The induction of major histocompatibility complex antigens by interferons (IFN) on 17 established tumour cell lines was investigated by radio binding. One bladder (Fen) and two testis lines (Tera I and Ha) lacked class I antigens and IFN-gamma failed to induce their expression. However, IFN-gamma upregulated these antigens on lines expressing low class I antigens (Tera II and EP2102) with little or no significant effect on high class I expressing lines (T24 and RT112). In one bladder line (Wil) IFN-gamma, whilst failing to alter monomorphic class I, upregulated polymorphic HLA-A2 and A3 antigens. None of the 17 lines expressed class II antigens, but could all be induced by IFN-gamma except T24, TccSup, Tera II and Lan lines. This defect was not due to the absence of IFN-gamma receptor, since under the same conditions intracellular adhesion molecule 1 was upregulated. IFN-alpha, whilst failing to have any effect on class II, induced class I antigens. IFN-beta showed no activity on either class I or II antigens when used alone. However, in combination, it inhibited IFN-gamma induced class II antigens. Thus, it may be possible to study cells from fresh tumours to preselect the minority of patients who might benefit from cytokine therapy.

Antibodies, Monoclonal↗
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↗
PubMed1992

Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis.

Forty-two families with two or more cases of testicular cancer have been reported to the UK Register for Familial Testicular Cancer, comprising two pairs of identical twins, 27 sets of other brothers (25 pairs, two triples), nine father-son pairs, two pairs of first cousins and two uncle-nephew pairs. In total 91 testicular tumours are described in 86 individuals (42 (46%) pure seminoma, 49 (54%) other germ cell tumours). The median age at diagnosis in these patients was significantly younger than that in a comparable series of non-familial patients (29 c.f. 32.5 years, P less than 0.01). In a case-control comparison of 794 testicular cancer patients, eight patients (1.0%) had a brother and four patients (0.5%) had a father with a previous diagnosis of testicular cancer at the time of their own diagnosis (and these families are all included in this report). Two out of 794 controls (0.3%) had a first degree relative with testicular cancer. The cumulative risk to a brother of a patient for developing testicular cancer by the age of 50 years was estimated to be 2.2% (95% C.I. 0.6-3.8%) which results in a relative risk of 9.8 (95% C.I. 2.8-16.7) in comparison with the general population. HLA Class I typing of 21 affected sib-pairs demonstrated four (19%) sharing two haplotypes, 13 pairs (62%) sharing one and four pairs (19%) sharing none. This did not differ significantly from the expected proportions of 25%/50%/25%. It is unlikely, therefore, that there is a major gene associated with testicular cancer predisposition within or closely linked to the major histocompatibility gene complex on chromosome 6.

Adolescent↗
PubMed1992

T cell immune response to cancer in humans and its relevance for immunodiagnosis and therapy.

Review of the relationship between the degree of immunosuppression and malignancy in patients on immunosuppressive drugs or immunosuppressed by HIV infection, postoperative blood transfusion or pregnancy provides the most convincing evidence of the importance of intact T cell immunity in resistance to cancer. Defective HLA class I and II antigen expression on tumours arising in non-immunosuppressed individuals and correlation of these changes with increased malignancy and diminished TIL provide the most convincing evidence that one factor necessary to ensure survival of most spontaneous tumours is mutation that enables tumour cells to escape rejection by cytotoxic T cells. These changes are less frequent in tumours in immunosuppressed patients, and preliminary data suggest that use of cytokine therapy is more successful in these tumours and the one in five spontaneous tumours demonstrating normal expression of HLA antigens and high levels of T cell infiltration. These observations suggest that future use of this therapy should be focused on these cases. All modalities of cancer therapy except hormone therapy (ie surgery, radiotherapy and chemotherapy) suppress immune responses. Defects of HLA antigen expression are less marked in early cancer. Combinations of immunotherapy with conventional treatment at presentation, including hormone therapy in view of data demonstrating regeneration of the thymus after castration, needs further investigation. Preliminary results from randomized trials involving nearly 300 individuals accidentally exposed to carcinogens demonstrated nearly 60% reduction of incidence of malignancy at 5 years in the arm receiving non-specific immunotherapy. If confirmed, such an approach might be more cost-effective as an approach for cancer prevention than organ specific cancer screening or vaccination against cancer associated viruses such as hepatitis B or papillomaviruses.

Animals↗
PubMed1991

Paired tumour infiltrating lymphocyte (TIL) and tumour cell line from bladder cancer: a new approach to study tumour immunology in vitro.

This paper reports the first example of tumour infiltrating lymphocytes (TILs) and a tumour cell line from the same individual and analyses their characteristics. The tumour cell line (CAT), derived from a patient with well-differentiated (G3pTa) TCC, has been in culture for 24 months and subcultured more than 100 times. Epithelial origin was established by electronmicroscopy and use of a range of monoclonal antibodies (Mabs) against cytokeratins. The TILs isolated from the same tumour expressed all the phenotypic characteristics of normal activated T cells and demonstrated low levels of cytotoxicity against the autologous tumour line (CAT). Comparison of cell surface molecules of these cells revealed the loss of HLA-B7, B44 and Bw6 from the CAT cells whilst maintaining HLA-A2, A3 and Bw4. Karyotypic analysis demonstrated three rearranged chromosomes (between chromosomes 4 and 11, 10 and 13, 11 and 17) on CAT cells. The potential that study of paired autologous tumour cells and TILs in culture offers for studying the role of MHC antigens in tumour rejection and the impact of different approaches to correcting the defect are reviewed.

Antibodies, Monoclonal↗
PubMed1991

Correlation between class I antigen expression and the ability to generate tumour infiltrating lymphocytes from bladder tumour biopsies.

Analysis of tissue sections from transurethrally resected bladder tumours using anti-CD3 antibody showed the presence of T lymphocytes in intra-epithelial layers in eight of 12 cases investigated. In a larger group of patients, Tumour Infiltrating Lymphocyte (TIL) growth was established from six of 19 cases using Interleukin-2 (IL-2) and conditioned medium (CM) and resulted in the expansion of TILs up to 100-fold. TILs from these individuals were phenotyped with W6/32 (anti-HLA-A,B,C), HB55 (anti-DR) and anti-CD3 antibodies using FAC sorter. The mean +/- s.d. frequency of positive staining with these antibodies were 96.7 +/- 4.0%, 87.5 +/- 10.0% and 82.5 +/- 7.8% respectively, indicating the activated nature of these T cells. The cytotoxic activity of these TILs against Daudi (ie, LAK activity) cell line at 25/1 E/T ratios varied from 26.3 +/- 3.2 to 62.8 +/- 5.2%. In one case where TILs and autologous tumour cell line were established, cytotoxicity studies showed low level of cytotoxicity against the autologous tumour cells (15.8 +/- 1.6%) compared with 62.8 +/- 5.2% against Daudi. Staining of tumour sections from these 19 individuals with W6/32 and BBM.1 revealed positive staining in six of six that developed TILs but only six of 13 (46%) cases, whose tumour failed to grow TILs (P less than 0.02, Fisher exact test). These results are indicative of the presence of IL-2 passageable T cells in bladder cancer biopsy and demonstrate that the successful expansion of these cells correlates with the normal expression of class I antigens on the tumour cells.

Antigens, CD↗
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↗
PubMed1991

Testicular cancer.

In testicular cancer epidemiology, the increasing recognition that germinal epithelial atrophy is the final common pathway in the development of this tumor has developed along with reports that elevated follicule-stimulating hormone levels at the time of diagnosis of first tumor correlate with risk of developing a second tumor. There is also evidence from experimental studies that atrophy is a complication of vasectomy, a recently reported risk factor. In the area of new diagnostic approaches, correlation of the rate of rise of tumor markers after orchiectomy in patients with metastases has defined a new risk factor for predicting drug-resistant disease. In the treatment of nonseminoma, it has been reported that use of adjuvant chemotherapy for stage I tumors with two courses of combination chemotherapy produces a relapse rate lower than that seen after surgical staging. For seminoma, chemotherapy results have improved, with nearly 100% of patients cured by combination regimens and 80% cured by single-agent carboplatin. This success is finally leading to questioning of the role of radiotherapy as adjuvant therapy for stage I tumors. A study using two courses of adjuvant carboplatin produced equivalent results and possibly less toxicity.

Dysgerminoma↗
PubMed1990

Selective and non-selective loss of immunoregulatory molecules (HLA-A,B,C antigens and LFA-3) in transitional cell carcinoma.

The expression of the major histocompatibility complex (MHC) class I and II antigens and lymphocyte function-associated antigen-3 (LFA-3) was investigated using immunohistochemical staining of bladder tissue sections from 18 patients with transitional cell carcinoma (TCC) and two normal bladder specimens. The expressions of HLA-A,B,C antigens varied greatly between different tumours. Complete loss was observed in one of 18 cases. Moderate to strong expression of HLA-A,B,C antigens was observed in 10 of 18 cases with the remaining seven cases showing either weak expression or expression on only a proportion of the tumour cells. Selective loss of HLA-Bw6 was seen in one of 18 cases. In many cases heterogenous and often focal expression of HLA-D products was seen. In one case tumour cells not expressing HLA-DR antigens were adjacent to strongly HLA-DR expressing non-neoplastic bladder epithelium, indicating a lack of inducible HLA-DR in the tumour cells. LFA-3 was undetectable in two of 18 cases with the remaining 16 cases showing moderate to strong expression of the molecule. These findings indicate that a substantial proportion of bladder tumours have one or more of a wide range of different alterations in the expressions of immunoregulatory molecules that could contribute to escape from immune surveillance.

Adult↗
PubMed1990

Composition of intact hormone and free subunits in the human chorionic gonadotrophin-like material found in serum and urine of patients with carcinoma of the bladder.

Ectopic-hCG production occurs in approximately 30% of urothelial cancers. However, the clinical features which might be expected to result from elevated hCG levels are rare. We now show that in six of seven metastatic and 20 of 21 localized (Ta-T4) positive hCG bladder cancer patients, only the free beta-subunit of hCG and its respective urinary breakdown product, beta-core, could be detected in clinical samples. Since only intact hCG is biologically active, this explains the discrepancy between biochemical and clinical findings.

Aged↗
PubMed1990

Alternatives to radiotherapy in the management of seminoma.

In a period from January 1978 to January 1989, 114 patients with seminoma have been managed, primarily in studies aimed at examining alternatives to radiotherapy. In a pilot study of single agent platinum in 27 previously untreated patients with metastatic seminoma, 82% remain progression-free and 89% alive and disease-free at 5 years compared with 81% progression-free and 88% alive and disease-free in a selected group of 16 previously untreated patients who received platinum-based combination treatment. Results from a pilot study of surveillance in 26 patients with stage 1 seminoma showed that 27% developed evidence of further disease (5 relapses, 2 second tumours) by 3 years, with all relapse patients salvaged by subsequent treatment. Because of the slow pace of relapse compared with malignant teratoma, with relapses occurring after 2 years, a pilot study was initiated to evaluate the effect of 2 courses of adjuvant carboplatin. The results to date in 25 patients suggest that with the use of modern antiemetics this regimen is as well tolerated as prophylactic radiotherapy. With a median follow-up of 16 months there has been 1 relapse subsequently salvaged by combination chemotherapy. A radomised trial is now justified to assess the quality of life and late toxicity of this approach compared with prophylactic radiotherapy.

Adolescent↗