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Biomedical subjects

R T Oliver

Publications and source records attributed to R T Oliver.

At least 127 records · Page 7Linked to original sources
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

Nephrectomy combined with perioperative alpha-interferon in the treatment of advanced local and minimally metastatic renal cell cancer.

alpha-Interferon produces a 15% response lasting on average 4-6 months in renal cell carcinoma, providing little justification for use as adjuvant treatment. Two observations, however, suggest that the benefits might be greater than predicted. In our studies in patients with small volume lung disease 59% responded (2 + 8/17) compared to 3% (0 + 2/64) for more advanced disease. Secondly, an animal intravenous metastasis model has shown a critical window of 24 h around the time of injection of tumour cells when treatment with interferon Ca produces durable complete remissions. In an attempt to capitalise on this observation, a feasibility study has been initiated to establish the safety of perioperative interferon. Patients received 3 MU daily for 3 days prior to operation and for 2 weeks after operation. Thirteen patients have been treated and all except one were discharged from hospital within 2 weeks. There have been two serious problems in the immediate post-operative period, one developed septicaemia and one had an episode of hypotension secondary to post-operative blood loss. One partial remission and one minor response was noted in the 9 patients with metastases and none showed accelerated tumour growth post-operatively. It is concluded that this approach is safe enough to be included in a randomised trial.

Aged↗
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↗
PubMed1991

Operative factors & tumor membrane antigen changes in escape from immune surveillance of bladder cancer.

1. Survival of skin allografts in mice is increased in proportion to the duration of anaesthesia to a degree that is equivalent to that achievable with a major immunosuppressive agent such as azothiaprine or antilymphocyte serum. 2. Immune cytochemical studies have demonstrated that bladder tumors which metastases express beta HCG and show variable degrees of loss of HLA class I antigens--features which mimic the behaviour of human trophoblast in protecting the foetus from maternal rejection. It is concluded that there may be a case for using such prognostic factors to define a sub group of patients in whom reconstruction of the bladder following cystectomy should be deferred until the patient has survived without metastases for a prolonged period.

Animals↗
PubMed1990

Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine 'normal' and malignant epithelial cells.

Expression of hCG and its free subunits by non-trophoblastic tumours is well recognised. Previously we reported hCG secretion by normal and malignant bladder epithelial cells in vitro. Here we examined culture medium from 83 different cell lines derived mainly from common epithelial tumours. Thirty-two of the cell lines were found to secrete hCG-like material into their culture media. Partial immunochemical characterisation showed that of these only choriocarcinoma and fetal tissue cell lines produced intact hCG and alpha subunit. The remaining 28 hCG-expressing epithelial cell lines, which are of mucosal origin, only secreted free beta subunit. Expression of free beta hCG by non-trophoblastic nonendocrine cells would appear to be especially characteristic of mucosal epithelia from the genitourinary and oral/respiratory tracts. Furthermore, this phenomenon may be characteristic of epithelium with transitional and/or squamous cell-like properties.

Carcinoma↗
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↗
PubMed1990

Prediction of response to radiotherapy in invasive bladder cancer.

The original pre-treatment histological sections from 125 patients with invasive (T2/T3) transitional cell bladder cancer treated by radical radiotherapy were studied; 63 tumours responded completely to radiation and 62 did not; 55 of 72 tumours containing areas of squamous metaplasia and 27 of 36 staining for beta-human chorionic gonadotrophin failed to respond to radiotherapy; 26 of 28 tumours showing both squamous metaplasia and beta-human chorionic gonadotrophin did not respond to radiation, whereas 40 of 45 tumours without either of these features responded. The DNA ploidy of 86 tumours in the series was measured by flow cytometry; 11 of 27 aneuploid and 30 of 59 diploid tumours responded to irradiation. Squamous metaplasia and beta-human chorionic gonadotrophin in bladder cancer indicate resistance to radiotherapy but DNA ploidy does not.

Adult↗
PubMed1990

Atrophy, hormones, genes and viruses in aetiology germ cell tumours.

This chapter reviews the evidence that testicular germ cell atrophy could be the final common pathway for all of the established and postulated risk factors for induction of testis tumours. The evidence from age incidence studies shows that the tumour peak incidence follows the curve of sexual activity in the male, and this provides the starting point for the argument that this tumour is dependent on endocrine factors for its induction. The data from epidemiological studies confirming the high frequency of atrophogenic events and occurrence of low sperm counts in more than 75% of patients provide the principal evidence in support of this hypothesis. The need for more information on hormone sensitivity of this group of tumours and in particular the more differentiated variety, ie seminoma, is highlighted. Information on levels of DNA repair enzyme activity as an explanation of radiosensitivity and chemosensitivity of this group of tumours is also needed. The relationship of HLA linked immune response genes to susceptibility to testicular atrophogenic virus infection needs further investigation, particularly in view of the recent introduction of widespread prepubertal vaccination against mumps virus, one of the most clearly identified testicular atrophogenic viruses. The paper concludes with an examination of the influence of carcinogens and radiation and how they relate to modern ideas of clonal evolution of tumours. The conclusion from this review is that testicular germ cell tumours provide an excellent model of the recent postulate of Ames et al, (1990) that for some cancers mitogenesis might precede mutagenesis, in contrast to the classical view produced from animal models that mutagenic induction is followed by mitogenic promotion.

Atrophy↗
PubMed1990

Clues from natural history and results of treatment supporting the monoclonal origin of germ cell tumours.

Recent observations have suggested that a major factor in the development of germ cell tumours may be excessive mitogenic stimulus developed because of failure of feedback suppression of the normal pituitary drive due to atrophic damage to germinal epithelium. With this observation and the increasing recognition that there is a common in situ stage which precedes both seminoma and malignant teratoma/non-seminoma there has been a polarisation of views regarding the relationship between seminoma and malignant teratoma/non-seminoma, with some authors viewing these two entities as separate unrelated transformational events while others hypothesise that seminoma is an interim stage of clonal evolution associated with increased malignant potential towards malignant teratoma/non-seminoma. This chapter reviews the clinical evidence supporting the concept of clonal evolution which arises from the observation that the modal DNA content of seminoma (3.6N) is intermediate between that of in situ carcinoma (4.2N) and malignant teratoma/non-seminoma (2.8N). These observations, taken with the observation that the median age of patients with mixed tumours containing both seminoma and non-seminoma elements (30 years) is intermediate between the slower growing seminoma (35 years) and faster growing malignant teratoma/non-seminoma (25 years), as well as studies of spontaneous regression, tumours in AIDS patients chemo/radio sensitivity and post mortem histology, provide the most convincing evidence supporting clonal evolution. However, these observations cannot explain the fact that some patients have more than one focus of tumour (which can be of different histological type) in a single testis with normal tubules in between, even if they have in situ carcinoma. An extreme manifestation is seen in patients who are treated and cured from metastases arising from one testicle who then die from metastases from a completely different histological type arising from a second transformation event of a germ cell in the contralateral testis. The conclusion from these observations is that it is indeed possible for polyclonal development of tumours to occur, as is seen for bladder and bowel tumours, but they do not detract from the concept that seminoma is an intermediate event in the evolution from in situ carcinoma to malignant teratoma/non-seminoma.

Adult↗
PubMed1989

Analysis of HLA antigens on germ cells in human semen.

Nucleated cells other than sperm (NCOS) were isolated from human semen by centrifugation on a Ficoll density gradient. Using tissue-specific monoclonal antibodies (mAb) greater than 99% of the NCOS were found to be sperm cell precursors (SpP). These cells were tested for the expression of class I and II (DR, DP and DQ) HLA antigens by using specific mAb. The anti-HLA class I and II and anti-beta 2-microglobulin mAb reacted with less than 1% of the NCOS. This was demonstrated by indirect immunofluorescence microscopy and fluorescence-activated cell sorter analysis. These results were similar to those obtained from testing germ cells in frozen sections of normal adult testis using the same panel of mAb. In mixed lymphocyte-NCOS cultures, the SpP failed to stimulate allogeneic lymphocytes even when different concentrations of cells were used. These results indicate little or no expression of HLA class I and II including the HLA-D (T cell-defined) determinant on the SpP, a phenomenon which could be of biological importance.

Antibodies, Monoclonal↗
PubMed1989

Human chorionic gonadotrophin expression and histological findings as predictors of response to radiotherapy in carcinoma of the bladder.

A retrospective analysis of the prognostic value of pretreatment histology and expression of human chorionic gonadotrophin (B-hCG) was carried out in 100 invasive (T2/T3) transitional cell carcinomas of the bladder treated in a uniform manner. After transurethral resection of the tumour, all patients received a course of radical radiotherapy, with salvage cystectomy for those who failed to respond. Forty-nine of 100 patients responded to radiation; thus 51 did not. Forty-seven of 60 (78%) patients whose tumours contained areas of squamous differentiation and 22 of 29 (76%) of tumours staining positively for HCG failed to respond to radiotherapy. Twenty-two of 23 (96%) patients with tumours that had both these features did not respond to radiotherapy. The other histological features studied (grade of tumour, necrosis, inflammation, vascular invasion, and growth pattern) appeared unrelated to each other or to clinical outcome.

Adult↗