Tumor markers of prognosis.
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Biomarkers, Tumor↗
Biomedical subjects
R C Leonard
Publications and source records attributed to R C Leonard.
Modulation of the cluster 1 and mucin antigens in human small cell lung cancer and other epithelial tumour cell lines after treatment with the differentiation inducing agent, sodium butyrate.
The expression of the human small cell lung cancer (SCLC) cluster 1 antigen and the human milk fat globule membrane (HMFG) antigen were studied in three SCLC, three lung adenocarcinoma, six ovarian adenocarcinoma and three colorectal adenocarcinoma cell lines before and after culture in the presence of the differentiation inducing agent, sodium butyrate. Before treatment, only SCLC and well differentiated ovarian cell lines expressed the cluster 1 antigen. After 4 days culture with sodium butyrate, expression of cluster 1 antigen was induced in poorly differentiated ovarian, colorectal and lung adenocarcinoma cell lines whereas existing antigen expression was enhanced in SCLC and well differentiated ovarian cell lines. The expression of the HMFG antigen was also modified. Induction of cluster 1 antigen correlated with increased levels of alkaline phosphatase in the treated cell lines, this enzyme being associated with a more differentiated state in colon and ovarian carcinoma cell lines. The pattern of induction of cluster 1 antigen expression suggests that several different epitopes of this antigen are recognised by the ten SCLC cluster 1 antibodies studied.
Adenocarcinoma↗
Establishment and characterisation of two new small cell lung cancer cell lines--one from a patient with previous familial retinoblastoma.
Two new small cell lung cancer (SCLC) cell lines have been established. The first, WX330, has been developed from a pleural effusion collected at presentation from a patient with extensive disease. The second, WX331, originated from a liver metastasis collected at post mortem from a patient who died of his SCLC disease. WX330 has been in culture for 4 years and WX331 for 11 months. Both cell lines have typical cytological features of SCLC, WX330 contains dense core granules on electron microscopic examination and both are tumourigenic in nude mice. Cell lines were analysed phenotypically using antibodies submitted to the Second International Workshop on SCLC Antigens by the immunoperoxidase method. WX330 is reactive with a wide range of SCLC and epithelial associated and WX331 with a more restricted group of antibodies of predominantly neuroendocrine and SCLC specificity. WX330 also reacts with an antibody against the multiple drug resistance-associated glycoprotein.
Adult↗
A familial RB1 mutation detected by the HOT technique is homozygous in a second primary neoplasm.
Using the hydroxylamine-osmium tetroxide (HOT) technique, we have identified a constitutional point mutation in the retinoblastoma susceptibility gene (RB1) which segregates with the expression of retinoblastoma in five affected family members. One member developed a second primary tumor, a small-cell lung carcinoma (SCLC), which metastasized to the liver. Analysis of liver tumour DNA revealed homozygosity for the constitutional mutation, a G----A transition at the fifth base of intron 21, resulting in the excision of exon 21 from the mRNA. This is the first demonstration of homozygotization of a constitutional RB mutation in a metastatic second primary tumour and underlines the usefulness of the HOT technique for identification of mutations of the RB1 gene.
Adult↗
The natural history of low grade non-Hodgkin's lymphoma and the impact of a no initial treatment policy on survival.
The natural history of low grade lymphoma and the influence of a 'no initial treatment' policy on survival were studied retrospectively in a group of 153 patients with stage II-IV low grade non-Hodgkin's lymphoma. The median follow-up was 85 months (range 45-229 months) and median survival of 50 months (range 14-220 months). Favourable outcome was significantly associated with the absence of B symptoms and a centroblastic/centrocytic (cb/cc) diffuse and follicular histological subtype and was inversely associated with increasing age. No significant differences in survival were found according to patient gender, site or stage of disease or whether the patients were participants in a clinical trial. Importantly, there was no survival disadvantage amongst the 56 patients who were initially untreated compared to those receiving other treatment modalities: initially untreated patients had a median survival of 75 months; 56 per cent were alive at 5 years and the median treatment free interval was 33 months. This favourable outcome persisted even after adjustment for other important prognostic variables. Further studies are needed to identify the characteristics of those patients with indolent disease in whom treatment may be deferred without adversely affecting survival.
Adult↗
A 10-year experience of tamoxifen as primary treatment of breast cancer in 100 elderly and frail patients.
Between 1977 and 1983 100 elderly women (median 76.3 years) with breast cancer were treated with tamoxifen as primary therapy. The median follow-up is 59 months. Sixty-eight responded (40 CR and 28 PR) with median response durations of 47 months and 26 months respectively. Twenty-two patients had disease stabilization for a median of 15.5 months and 10 had progressive disease. The median time to best response was 13.5 weeks for patients achieving CR and 14 weeks for those with PR. Oestrogen receptor values were obtained in 37 patients of which two patients had no ER detectable. Sixty-seven per cent of ER-unknown patients responded compared with 74% of ER-rich. Likelihood of response did not appear to depend upon T-stage or age. Survival was better than that of an unmatched historical group treated with surgery/radiotherapy and compares favourably with recent reports. Although 35% have died of breast cancer, 25% died of other causes and 22% remained free of recurrence at the time of reporting or at death. Only 11% underwent subsequent mastectomy/lumpectomy and the most frequent subsequent treatments were radiotherapy to the breast (32%) and further hormonal therapies (40%). Tamoxifen is a practical primary therapy of breast cancer in elderly and frail women obviating the need for surgery in a high proportion of cases.
Aged↗
Immunocytological detection of residual marrow disease at clinical remission predicts metastatic relapse in small cell lung cancer.
A panel of monoclonal antibodies against neural and epithelial associated antigens was used to examine bone marrow from patients in clinical remission from small cell lung cancer (SCLC). A standard peroxidase-antiperoxidase technique and Ficoll-Hypaque enrichment were used to detect SCLC-like cells at the 1-2% level of contamination in 8 of 12 patients who were disease free by conventional criteria, including routine marrow cytology and histology and endobronchoscopic biopsy or cytology. Six of these patients ultimately relapsed, with metastatic sites found between 2 and 6 months after restaging. Furthermore, 6 patients had undergone chemointensification including autologous marrow rescue with radical irradiation to the primary lung tumor. Four of these 6 subsequently relapsed, also with metastatic sites. Of the 4 patients without bone marrow metastases at restaging using this technique, 2 relapsed, with cells found at the primary site, and 2 remained in complete remission. Serum free cell culture was attempted in 9 of 12 cases and SCLC-like cell colonies grew, in suspension, in 4. The SCLC-like nature of these cells has been confirmed by electron microscopy in 1 case and by repeat immunocytochemistry for small cell associated antigens in 3 cases. Bone marrow positivity using these techniques appears to predict a high risk of metastatic relapse regardless of further therapy.
Adult↗
A phase II trial of mitomycin C and 5-fluorouracil as second-line therapy in advanced breast cancer.
Fifty-five patients who had relapsed or progressed from chemotherapy for advanced disease were treated with mitomycin C and 5-FU on a 6 weekly regimen. After a median of 2 cycles of therapy the overall response rate was 12% with no complete responses. Significant leucopenia but no thrombocytopenia was seen and despite the low overall response rate the regimen was tolerable and did produce responses in patients primarily resistant to Adriamycin combination chemotherapy. Low overall activity indicates the need for more effective second line treatment.
Adult↗
On the distributions of spontaneous chromosomal aberrations in human peripheral blood lymphocytes in culture.
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Adolescent↗
Prognosis at presentation of small cell carcinoma of the lung.
Prognostic factors in 411 patients with small cell lung carcinoma have been retrospectively analysed. Univariate analysis of continuous variables showed that prognosis was worse with deteriorating performance status, extensive disease, positive bone scan, increasing age, elevated total white cell count, alkaline phosphatase, lactate dehydrogenase, and decreased serum chloride and albumin. Low serum sodium was less clearly associated with poor survival. Cox multivariate regression showed that performance status, disease extent, age and raised lactate dehydrogenase and white cell count were independent prognostic factors. When disease extent was excluded from analysis, performance status, age, total white cell count, lowered serum chloride and raised lactate dehydrogenase were significant independent prognostic variables.
Adult↗
Prognostic factors for survival in soft tissue sarcoma.
Between 1975 and 1984, 125 cases of histologically confirmed soft tissue sarcomata (STS) were registered in the Department of Clinical Oncology in Edinburgh. Of these, 100 were eligible for analysis of prognostic factors. The overall 5-year survival rate was 21.5%. Univariate analysis demonstrated that extent of surgery, radical versus palliative or no radiotherapy, mass as a presenting symptom, metastases at presentation, site, histological type, mitotic activity, grade and UICC stage all had a statistically significant effect on survival. Analysis using the proportional hazard regression model was performed on the 87 patients for whom all variables were recorded. When all histological and clinical features and treatment modalities were included in the model then radiotherapy, surgery, necrosis, sex and mitoses were identified as independent prognostic variables. When symptoms and treatment were excluded then the multivariate analysis identified sex and mitotic activity as independent parameters. For the 33 superficial STS with tumour size recorded multivariate analysis revealed size, necrosis and cellularity as independent prognostic variables. For the 31 deep STS histological type, sex, surgery and radiotherapy were identified as independent prognostic parameters.
Adolescent↗
Anti-emetics and cancer chemotherapy.
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Antiemetics↗
Potentiation of cisplatin by alpha-interferon in advanced non-small cell lung cancer (NSCLC): a phase II study.
Studies in experimental human lung cancer models have suggested that interferon may enhance significantly the response to some cytotoxic drugs. We have performed a phase II study of cisplatin (100 mg/m2 q.21 or 28 days) and alpha-2 interferon (3 or 5 MU three times weekly) in 68 patients with advanced non-small cell lung cancer and good performance status. As toxicity was acceptable, the dose of interferon and schedule of cisplatin were increased at the midpoint of the study. 46% (11/24) of patients with squamous carcinoma responded and an overall partial response rate of 30% was attained in 60 evaluable patients. There was no potentiation of haematological, renal or neurological toxicity but nausea and vomiting were severe. These results suggest that the combination has activity in this usually refractory disease.
Adult↗
Allele losses on chromosome 17 in human epithelial ovarian carcinoma.
16 epithelial ovarian carcinomas (12 serous, 2 mucinous and 2 endometrioid) and 2 benign ovarian adenomas were studied using recombinant DNA technology to compare loci on chromosome 17 in germ-line and tumour DNA. Four polymorphic probes mapping to 17p and one mapping to 17q were used. There was a high frequency of allele loss on 17q/(77%) and a slightly lower frequency on 17p (69%). These findings probably indicate loss of tumour suppressor genes which are of fundamental importance in the genesis or progression of epithelial ovarian carcinomas.
Adenoma↗
Randomised trial comparing prednimustine with combination chemotherapy in advanced ovarian carcinoma.
A total of 76 patients with advanced epithelial ovarian carcinoma were randomised to receive 6 months of treatment with either a combination of hexamethylmelamine, 5-fluorouracil, cisplatin and prednimustine or prednimustine alone following initial surgery. Pathologically confirmed response rates were 35% for combination chemotherapy and 28% for prednimustine, and the overall survival was identical for the two groups. Seven patients achieved a pathologically defined complete response, one of whom relapsed at 8 months; the others remain disease-free 18-36 months (median, 23 months) after presentation. The extent of initial surgery significantly affected the survival of patients receiving prednimustine but not of those receiving combination chemotherapy. Prednimustine can produce durable responses in advanced ovarian cancer using a schedule that results in negligible toxicity.
Altretamine↗
Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. II. Extension of age range.
We have previously reported on a cytogenetic-epidemiological study of chromosomal aberration and sister-chromatid exchange (SCE) frequencies in peripheral blood lymphocytes (PBL) of a cohort of 353 healthy employees of the Brookhaven National Laboratory (Bender et al., 1988). This sample has now been increased in order to extend the age range represented and, incidentally, the representation of non-white subjects. In total, the data now include chromosomal aberration information from 108,950 cells and SCE information from 25,397 cells from 613 samples from 493 subjects. Neither the mean frequencies of any of the chromosomal aberration types nor the mean frequency of SCE have changed notably through the addition of the new subjects and samples. The mean age at sampling of the population is now 43.1 years with a range of from 1.1 to 83.7 years. However, we still find no significant relationship of the frequency of any conventional aberration category to age with the single exception of the dicentric chromosome, which now shows a positive regression (p = 0.001). The raw mean SCE frequencies show a statistically significant increase with subject age, but when cigarette smoking status is taken into account, no significant age relationship is found. As with the earlier samples, neither aberration nor SCE frequencies was influenced by race. Mean SCE frequencies, measured in non-smokers, were about 5% higher in females than males. Only one aberration category, "supernumerary acentric fragment", was significantly related to sex. This "aberration", known to constitute early centromere separation of an X chromosome, is much more common in females than in males and, in the females, increases significantly with increasing subject age.
Adolescent↗
Small cell lung cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Serum placental-like alkaline phosphatase (PLAP): a novel combined enzyme linked immunoassay for monitoring ovarian cancer.
A new combined enzyme linked immunoassay (ELISA) was developed to measure both serum placental-like alkaline phosphatase (PLAP) activity (PLAPA) and concentration (PLAPC) in the same microtitre plate using an Imperial Cancer Research Fund monoclonal antibody, designated H17E2. PLAP A and PLAP C were determined together with an existing marker, CA125 in 397 serial samples from 87 patients with epithelial ovarian cancer. Retrospective assessment showed the sensitivity to increase from 73% with CA125 alone, to 88% using CA125 and PLAP A, and to 93% with all three markers in 261 samples from the patients with known active disease at the time of sampling. When the results for all 397 samples were included in the analysis, however, the specificity, sensitivity, accuracy and predictive powers of this monoclonal antibody were not sufficiently high to assist in the prospective follow up of patients with ovarian cancer. This was due to a significant number of false positive and false negative results. Our data indicate that PLAP A or PLAP C estimation with H17E2 may, therefore, only be of value in the management of those patients with known active disease who are already known to be "marker positive" for this antigen.
Adenocarcinoma↗