PubMed Health⌕ Search

Biomedical subjects

M Catterall

Publications and source records attributed to M Catterall.

At least 19 recordsLinked to original sources
PubMed1994

Transforming growth factor-alpha-Pseudomonas exotoxin fusion protein (TGF-alpha-PE38) treatment of subcutaneous and intracranial human glioma and medulloblastoma xenografts in athymic mice.

Epidermal growth factor receptor (EGFR) is amplified or overexpressed in many malignant gliomas and other primary brain tumors but is low or undetectable in normal brain. In the present study, this differential expression has been exploited for targeted brain tumor therapy using a TGF-alpha-Pseudomonas exotoxin recombinant toxin, TGF-alpha-PE38. In vitro experiments demonstrate that the cytotoxicity of this fusion protein is primarily determined by tumor EGFR expression and that TGF-alpha-PE38 cytotoxicity is abolished by pretreatment with excess epidermal growth factor. Treatment with i.p. TGF-alpha-PE38 in nude mice bearing glioblastoma or medulloblastoma s.c. xenografts produced tumor regression and growth delay. For intracranial xenograft implants treated with i.p. TGF-alpha-PE38, significant increases in median survival were noted only for tumors with the highest EGFR expression. However, intracranial tumors treated with a single intratumoral injection of TGF-alpha-PE38 showed increased survival in all xenografts tested. These results indicate that TGF-alpha-PE38 is active against primary human brain tumors ranging from moderate to high EGFR expression. For intracranial tumors, however, the higher survival rates produced by intracranial injection of TGF-alpha-PE38 than by continuous i.p. administration suggest that increased drug clearance or impaired drug delivery reduces the efficacy of systemic TGF-alpha-PE38. Direct delivery of TGF-alpha-PE38 into brain tumors by controlled-release biodegradable polymers or intratumoral implanted catheters, or intrathecal administration into the colony stimulating factor of patients with leptomeningeal metastasis, may represent clinically useful applications of recombinant toxin therapy in tumors with high EGFR expression.

Animals↗
PubMed1989

Neutron therapy at Hammersmith Hospital 1970 to 1985. A re-examination of results.

Since the Hammersmith cyclotron was removed, the earlier therapy results have been extensively re-examined. The overall experiences can be summarized as follows: 1. A total neutron dose of 1560 cGy given in twelve equally spaced fractions over 20 days seems to be the optimum. Neutrons, therefore, provide a treatment option with great advantage with respect to patient management. 2. Rapid tumour regression is an important often ignored effect, leading to a quick relief of pain and other serious symptoms in the patient. 3. Due to the high incidence of complete regression complicated surgery can be avoided in many cases. Tissue deficits can be often covered by modern methods of surgery repair. 4. Local control rates are as high as 60 to 80% of the advanced tumours. They improve the quality of life and reduce the cost of continuing patients' care.

Evaluation Studies as Topic↗
PubMed1987

The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy.

The conventional treatment for cancer of the salivary glands is surgery, with or without X ray therapy. In advanced tumors (Stage III and IV), local control and 5-year survival rates are less than 35%. Radical surgery severs the facial nerve in the majority of operations on parotid gland tumors. Local control of unresectable salivary gland tumors was achieved, in 74% of cases, by fast neutron therapy. From the MRC cyclotron at Hammersmith Hospital neutrons were given to 65 patients, with locally advanced or recurrent tumors, 89% of which were Stage IV. Local control and 5-year survival rates were 72% and 50%, respectively. The facial nerve was not damaged by neutron therapy. In patients with parotid gland tumors, 77% regained or maintained function. Function was lost in 14% through recurrence and 9% remained paralyzed. The results were achieved using beams from primitive machines with serious disadvantages. The results from neutrons implicate improvements for locally advanced tumors of non-epidermal origin in other sites of the body, especially with the high energy neutrons now available from modern cyclotrons.

Adult↗
PubMed1987

A comparison of clinical and laboratory data on neutron therapy for locally advanced tumors.

Experimental results suggest advantages for neutrons where cells are hypoxic, in tumors which are slowly growing and also in a relative sparing of bone damage. The neutrons available at Hammersmith were of 7.5 MeV energy and produced a poorly penetrating beam, unsuitable for treating tumors in the pelvis and abdomen. Patients with locally advanced tumors in superficial sites were therefore selected to assess the effects of neutrons on normal and malignant tissues. One hundred and eight-nine patients had between them 191 locally advanced (T4 N0-3) tumors in the oral cavity, paranasal sinuses, salivary glands, and breast. Neutron therapy resulted in complete regression in 84% of which 13% subsequently recurred. Median survival for the whole group was 32 months. Twenty-eight other patients had advanced tumors of the head and neck which were recurrent after X ray therapy and other treatments; 82% of these completely regressed for more than 1 year. Complications appeared in 27% of patients not previously treated and in 46% who had already undergone X ray therapy. Seventy-four per cent of complications started in the skin. With neutrons of this energy there is minimal sparing of the skin and uneven distribution of dose resulting in "hot" spots. These affected skin, subcutis, and muscle. The high rates of control in these large tumors, the low incidence of bone necrosis, and the repair of some bones eroded by tumor correlate well with the experimental data. There was rapid regression of the tumor and close correlation between early and late effects on skin and subcutis. These two observations may relate to the fractionation, total dose, and overall time of treatment of 1560 cGy neutron dose given in 12 fractions over 28 days.

Breast Neoplasms↗
PubMed1987

Fast neutrons in the treatment of locally advanced breast cancer.

The clinical investigation of fast neutrons at Hammersmith Hospital included 17 patients who between them had 20 T4 breast cancers. The majority of these tumours were ulcerated and all were painful. Ten had recurred after multiple other therapies. Complete local regression was achieved in all but one (95%) and no tumour recurred. Symptoms were relieved in all cases. Median survival was 26 months. Three patients developed small areas of skin necrosis following trauma of previous radiation. All the neutron treated breasts became fibrosed, but this was painless. Neutron treatment needed only 12 attendances over 28 days, in contrast to the best results from photon therapy which required 6-7 weeks followed by implant of radioactive wire and/or surgical excision. One patient who had bilateral tumours received neutrons to the left breast and X-ray therapy (photons) to the right. The photon treated tumour did not completely regress and recurred. The neutron treated one completely regressed and did not recur. Neutrons were also more effective than tamoxifen which causes complete regression in only about 30% of cases. It is suggested that neutron therapy is indicated for locally advanced tumours which do not respond to hormones. Since metastases were a common cause of death, there remains a need for an effective adjuvant treatment, acceptable to elderly patients.

Adult↗
PubMed1986

Re-irradiation of advanced tumors of the head and neck with fast neutrons.

Twenty-eight patients who had received radical treatment with X rays to tumors of the head and neck presented with advanced recurrent tumors, 23 of them had also undergone surgery and 10 had more than one operation. Seven had also received chemotherapy. They were treated with neutrons to a tumor dose of 1560 cGy in 12 fractions over 26 days using the techniques of the Hammersmith Unit. Twenty-three of the tumors (82%) underwent complete regression that was maintained in 15 for at least 12 months. Despite the damage done by the previous radiation and surgery to the normal tissues, 15 patients had no complications following neutron therapy. In six patients, there was major necrosis, in seven others, this was minor. Eight tumors recurred. Five patients responded with partial regression of their tumors. The median survival was 20 months (range 4-69 months).

Fast Neutrons↗
PubMed1986

The late effects on normal and malignant tissues from 7.5 MeV neutrons in the treatment of advanced mouth cancer.

Seventy of 104 patients with advanced oral cancer lived more than one year after neutron therapy and a local control rate of 74% was obtained. Eighty-nine per cent of these tumours were stage 3 or 4. There were 24 adverse late effects of which 20 involved soft tissues and four involved bone. Thirty eight of 40 mandibles which were normal before treatment remained so despite the curative dose which was given. Seven of 15 mandibles eroded by tumour became clinically normal after treatment. Eight per cent variation in dose was easily discernible in the skin and subcutis. These clinical findings correlated with the low energy of the neutrons and with the relative sparing of bone by neutrons.

Carcinoma, Squamous Cell↗