Biomedical subjects

G C Jayson

Publications and source records attributed to G C Jayson.

42 records · Page 3Linked to original sources

PubMed1996

Carcinomatous meningitis in solid tumours.

Carcinomatous meningitis (CM) is an uncommon but devastating complication of malignancy. The management is controversial and clear recommendations cannot be made because: 1) Most series include patients with CM that has arisen from different primary malignancies which are associated with different median survival intervals. 2) There have been no prospective randomised investigations of treatment modalities in patients with CM from a particular tumour type. 3) The definition of response varies from one report to another so that some response rates refer to cytological changes in the CSF while others take clinical, cytological and biochemical parameters into account. 4) Reports include patients with and without parenchymal metastases and the natural history of carcinomatous meningitis in the two situations may differ. The median survival of solid tumour carcinomatous meningitis (excluding leukaemia and lymphoma) is approximately 2-3 months and patients with breast cancer have the longest survival (median 3 months). Currently patients are treated with radiotherapy to part or all of the neuraxis with either intrathecal or intravenous chemotherapy but the relative contribution of these modalities to survival or quality of life remains unknown. Approximately 50% of patients with carcinomatous meningitis die from other causes, including systemic disease. The two most important endpoints for the patient, neurological improvement and overall survival, are seldom used in isolation in the literature. Many reports have focused on surrogate markers of response, namely biochemical and cytological data points but the correlation between clinical status and these parameters is poor because of differences between lumbar and ventricular CSF and disturbances of CSF flow in CM. The current literature does not provide clear guidelines for the treatment of this condition. Multicentre, prospective, randomised trials should be conducted that address questions of most relevance to the patient, namely neurological status and overall survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

A phase I trial of bryostatin 1 in patients with advanced malignancy using a 24 hour intravenous infusion.

Bryostatin 1 is a macrocyclic lactone derived from the marine invertebrate Bugula neritina. In vitro, bryostatin 1 activates protein kinase C (PKC), induces the differentiation of a number of cancer cell lineages, exhibits anti-tumour activity and augments the response of haemopoietic cells to certain growth factors. In vivo, bryostatin 1 is also immunomodulatory, but the range of tumours which respond to bryostatin 1 in xenograft tumour models is mostly the same as the in vitro tumour types, suggesting a direct mode of action. Nineteen patients with advanced malignancy were entered into a phase I study in which bryostatin 1 was given as a 24 h intravenous infusion, weekly, for 8 weeks. Myalgia was the dose-limiting toxicity and the maximum tolerated dose was 25 micrograms m-2 per week. The myalgia was cumulative and dose related, and chiefly affected the thighs, calves and muscles of extraocular movement. The mechanism of the myalgia is unknown. CTC grade 1 phlebitis affected every patient for at least one cycle and was caused by the diluent, PET, which contains polyethylene glycol, ethanol and Tween 80. Most patients experienced a 1 g dl-1 decrease in haemoglobin within 1 h of commencing the infusion which was associated with a decrease in haematocrit. Radiolabelled red cell studies were performed in one patient to investigate the anaemia. The survival of radiolabelled red cells during the week following treatment was the same as that seen in the week before treatment. However, there was a temporary accumulation of radiolabelled red cells in the liver during the first hour of treatment, suggesting that pooling of erythrocytes in the liver might account for the decrease in haematocrit. Total or activated PKC concentrations were measured in the peripheral blood mononuclear cells (PBMCs) of three patients for the first 4 h of treatment and during the last hour of the infusion. This showed that PKC activity was significantly modulated during the infusion. Bryostatin 1 is immunomodulatory in vitro, and we have confirmed this activity in vivo. An investigation of the first three cycles of treatment in seven patients showed an increased IL-2-induced proliferative response in peripheral blood lymphocytes and enhanced lymphokine-activated killer (LAK) activity. A previously reported rise in serum levels of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF 1) was not confirmed in our study; of nine patients in this study, including patients at all dose levels, none showed an increase in these cytokines.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1994

Carcinomatous meningitis in patients with breast cancer. An aggressive disease variant.

BACKGROUND: Carcinomatous meningitis is a rare and often devastating complication in patients with breast cancer, and the treatment is controversial. METHODS: A retrospective analysis of 35 patients with carcinomatous meningitis from breast cancer was performed to define the biology of the disease and to guide treatment. RESULTS: An aggressive variant of breast cancer was revealed: meningeal metastasis complicates less than 3.5% of cases of metastatic breast carcinoma. Sixty-seven percent of these patients had tumors that were lobular or combined lobular/ductal histology; the median intervals from primary treatment to disease recurrence and from recurrence to death were 10.9 and 15 months, respectively. The median survival after diagnosis of carcinomatous meningitis was 77 days. The most significant prognostic factor was the Karnofsky performance status (KP) at presentation of meningeal disease. Patients with a KP greater or equal to 70 survived a median of 313 days, whereas those with a KP of 60 or less survived for a median of 36 days (P = 0.0002). In addition, there was a trend suggesting that the response 2 weeks after treatment was initiated, correlated with survival. CONCLUSIONS: Carcinomatous meningitis from breast carcinoma is an aggressive metastatic complication with a poor prognosis. The authors suggest that patients with a poor KP (< 70) should be treated symptomatically and those with a good KP (> or = 70) should receive more aggressive treatment. The patients' survival in this study compared well with other reports, and yet, only one patient was treated with intraventricular chemotherapy. Therefore, these data question the superiority of intraventricular treatment versus other modalities.

Adult↗

PubMed1994

Basic fibroblast growth factor increases the multiplication and migration of a serum-free derivative of CACO-2 but does not affect differentiation.

Basic fibroblast growth factor (bFGF) is found in the extracellular matrix and around the endothelial and epithelial cells of some human colon carcinomas. It is believed to play a role in angiogenesis, but in addition, recent data suggest that it can directly stimulate mitogenesis in some colon carcinoma cell lines. To clarify the role of bFGF in human colon carcinoma, we developed a model of Caco-2 which grew in serum-free conditions so that the effect of bFGF on multiplication, migration, and differentiation could be studied in defined conditions. Through morphological and biochemical studies in serum-free conditions, we demonstrated that this subline of Caco-2 differentiated spontaneously on reaching confluence. Using this model, we found that bFGF did not affect differentiation but that multiplication and migration were increased. The implication of these findings is that bFGF, released from the extracellular matrix by invading cells or produced by neovascular endothelial cells, can increase the mitogenic rate and migratory potential of colon carcinoma cells. In addition, the dual role of bFGF in stimulating colon carcinoma cells directly and promoting angiogenesis suggests that anti-bFGF strategies could form the basis of a novel approach to the treatment of colon carcinoma.

Cell Differentiation↗

PubMedDate not supplied

Stage- and CA125-related survival in patients with epithelial ovarian cancer treated at a cancer center.

Current accepted prognostic indicators in ovarian cancer include performance status, surgical (FIGO) staging, and residual disease after operation. Here we present data from a prospective analysis of patients with ovarian cancer treated at the Christie Hospital. We confirm the independent prognostic effects of FIGO staging, performance status, and residual disease in our group of patients and furthermore show that CA125 levels at presentation to the oncology service are of independent prognostic significance (P= 0.02). We present survival data and show that the 3-year, cancer-specific survival for stage I disease is 90%. We postulate that this good survival may in part be due to the use of computed tomography scanning at presentation to allow accurate staging. Further clinical trials are needed to test whether combinations of surgical, histologic, biochemical, and radiologic parameters can be used to identify a population with such a good prognosis that adjuvant therapy is not required.

Adenocarcinoma↗

PubMedDate not supplied

Development of a modified hollow fibre assay for studying agents targeting the tumour neovasculature.

BACKGROUND: Previous studies have shown extensive vascularisation surrounding subcutaneously implanted fibres when the duration of the US National Cancer Institute (NCI) hollow fibre assay was prolonged. MATERIALS AND METHODS: The feasibility of adapting the NCI assay for evaluating agents targeting the tumour vasculature was investigated in vitro and in vivo. Finally, in the optimised assay, changes in neovasculature formation around the fibres following treatment with the anti-vascular agent paclitaxel were quantified by immunohistochemistry. RESULTS: Correlations between cell number seeded, time in culture and vascular endothelial growth factor (VEGF) secretion were seen. In vivo studies showed that transplanting single rather than 3 fibres at a site reduced inflammation, reducing the length of the fibre transplanted, as did without any significant loss in cell growth over 21 days. A statistically significant reduction in neovascularisation surrounding the fibres was seen accompanying paclitaxel treatment. CONCLUSION: Modifications made here to the NCI hollow fibre assay demonstrate its potential for analysing anti-tumour vasculature agents.

Angiogenesis Inhibitors↗