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Biomedical subjects

J Waxman

Publications and source records attributed to J Waxman.

At least 91 records · Page 5Linked to original sources
PubMed1992

Sequential interleukin-2 and alpha interferon for renal cell carcinoma and melanoma.

There is a theoretical basis for the synergy of interleukin-2 (IL-2) with other cytokines. We have investigated sequential treatment with IL-2 and alpha interferon. 1 of 22 patients with metastatic renal cell carcinoma had a partial response and one a minimal response to continuous infusion IL-2 but none of the 9 patients with melanoma responded. 16 of 17 patients with renal cell cancer, and 8 with melanoma, were then treated with alpha interferon. 2 patients with renal cell cancer responded to alpha interferon with sustained remissions of 30 and 40 months; both had responded to IL-2. The investigation of combination therapy with other cytokines is suggested, by these unusually long responses to alpha interferon.

Adolescent↗
PubMed1992

Patterns of survival in patients with advanced Hodgkin's disease (HD) treated in a single centre over 20 years.

A total of 164 consecutive adults with newly confirmed stage IIIB, IVA or IVB Hodgkin's disease (HD) commenced cyclical combination chemotherapy comprising mustine, vinblastine, prednisolone and procarbazine (MVPP) every 6 weeks (145 patients) or minor variants (19) at St Bartholomew's Hospital between 1968 and 1984. The median follow-up period is 14 years. Complete remission (CR) was achieved in 97/164 (59%) and partial remission (PR) in 23/164 (14%) with lesser responses or death being documented in 44. Achievement of CR correlated with stage, serum albumin and serum beta2 microglobulin level at presentation on univariate and multivariate analysis; 55/97 (58%) remain in continuous CR, the median duration of remission not having been reached. Twelve patients died in first remission; there have been 30 recurrences, one occurring after 13 years. Second remission was achieved in 17/30; 6/17 remain in continuous second remission and two have died in second remission. There have been nine second recurrences, third remission being achieved in 6/9. Two continue in third remission, two patients have died in third remission: 82/164 patients are alive with a minimum follow-up of 6 years. Eighty-two patients have died; 66 with evidence of HD, six with second malignancy, one each of haemorrhage and infection, eight of unrelated causes, the cause of death was unknown in one. The overall median survival from presentation is 14 years, being the same for patients in CR and PR with minimal residual abnormality (good partial remission, GPR), and being better for those for whom remission was achieved than those for whom it was not. The median survival following first recurrence is 4 years, being significantly longer for younger patients (less than 50 years). These results emphasise the importance of long-term follow-up to determine the clinical course of HD and are vital for planning experimental chemotherapy at the time of early treatment failure or recurrence.

Adolescent↗
PubMed1992

Hormonal management of prostate cancer.

In advanced disease, androgen deprivation remains the usual treatment. The completion of current trials is awaited to confirm whether total androgen blockade will prolong survival. To make further advances in treatment the fundamental biology of the prostate cell, benign or malignant, and its relationship to endocrine manipulation, must be understood. This may then lead to an understanding of clonal escape mechanisms in transformed cells and the clinical correlate of escape, relapse.

Aged↗
PubMed1992

Bladder cancer: inter-relationships between chemotherapy and radiotherapy.

There has been increasing interest in the role of chemotherapy as primary treatments for patients with urothelial cancer and because of the poor prognosis of locally advanced tumours with conventional treatment, trials have been initiated comparing radiotherapy with chemotherapy as primary therapies. In this context it is important to assess the relationship between the responses to chemotherapy and radiotherapy, and this we have examined in 64 patients treated with MVMJ (methotrexate, vinblastine, mitozantrone and carboplatin). Either a complete or a partial response was found in 29 of the 64 patients, 15 had stable disease and 13 had progression of disease. Seven patients died within the first treatment month. The survival of the responding patients ranged from 114 to 1184 days. Six of 15 patients who had had pelvic irradiation prior to chemotherapy responded to MVMJ, the maximum duration of response being more than 3 years. Twenty-two patients had radiotherapy following their chemotherapy. One of 13 patients not responding to MVMJ had a transient response to radical radiotherapy. Only 1 of 9 patients responding to chemotherapy and then relapsing responded to subsequent radical radiotherapy. Patients with metastatic disease or with recurrent disease after radiotherapy have a worthwhile chance of responding to chemotherapy and achieve durable remissions. In contrast, radiotherapy appears relatively ineffective in patients whose disease progresses or relapses after chemotherapy given as primary treatment with curative intent.

Adult↗
PubMed1992

Peripancreatic lymph node gastrinoma in a patient with Zollinger-Ellison syndrome.

The case of a patient who had Zollinger-Ellison syndrome caused by a primary peripancreatic lymph node gastrinoma is presented. Accompanying diffuse pancreatic islet cell hyperplasia, a well-documented occurrence in hypergastrinemia, was present. A perforated esophageal ulcer in a Barrett's esophagus led to right-sided necrotizing pleuritis, septicemia, and death. The diffuse parathyroid hyperplasia also noted in the patient is thought to be secondary to chronic hypertensive renal failure rather than MEN-I syndrome.

Aged↗
PubMed1991

Quantitative measurement of monoclonal antibody distribution and blood flow using positron emission tomography and 124iodine in patients with breast cancer.

The uptake and in vivo quantitation of monoclonal antibodies (MAbs) has been measured non-invasively using positron emission tomography (PET) and 124iodine in 9 patients with breast ductal carcinoma. Blood-flow measurements were also made using 15oxygen-labelled water and PET to evaluate antibody delivery; 7 patients were studied with HMFGI antibody and 2 patients with a non-specific antibody. Tumour uptake ranged from 2-7.7 x 10(-3)% of injected dose per gram of tissue. Values for normal tissues including liver, lung and bone were also obtained. In 2 out of 7 patients studied with the specific antibody, uptake was greater than that seen with the non-specific antibody. There was no correlation between antibody uptake and blood flow. This report exemplifies the potential of PET for the non-invasive and accurate quantitative assessment of targeted antibody which is a prerequisite to therapy.

Adult↗
PubMed1991

Gonadotrophin-releasing hormone: physiological significance and relevance to cancer.

Gonadotrophin releasing hormone (GnRH) is a decapeptide released by the hypothalamus. The binding of the peptide to pituitary receptors leads to the activation of second messenger systems. The physiological outcome of the exposure of pituitary cells to GnRH is the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH). Continued exposure of these receptors to high concentrations of the peptide desensitises the receptor, thus inhibiting the release of gonadotrophins. This paradoxical effect has proved to be beneficial in the clinic where long-acting and enzyme-resistant analogues are used to inhibit the pituitary-gonadal axis, for example in the treatment of advanced prostatic cancer. In addition GnRH-analogues may affect tumour cells directly as observed in vitro. These direct effects have been described as inhibitory but recent data suggests that low concentrations of GnRH-analogues may stimulate short term growth of prostatic cancer cells in vitro. GnRH shares many other common characteristics with peptide growth factors, including common second messenger systems and receptor desensitisation on prolonged exposure to the ligand. It is possible that the direct inhibitory effects of GnRH-analogues are mediated through the desensitisation of tumour GnRH receptors, as suggested by recent observations. The nature and mechanism of the direct anti-tumour effect is important to understand and to promote the therapeutic efficacy of GnRH-analogues in the clinic.

Amino Acid Sequence↗
PubMed1991

A new understanding of the hormonal regulation of endocrine dependent cancer.

In the last decade there have been major developments in our understanding of the hormonal control of cancer. The steroid receptor has been characterized and its gene cloned. Peptide hormone receptors and their ligands have been identified within the cancer cell providing supporting evidence for the significance of the autocrine hypothesis in the regulation of cell growth. Conventional wisdom describes different levels at which hormonal therapies for endocrine related malignancies operate, regulating cell growth by decreasing levels of circulating sex steroids upon which the cell depends. Current theories incorporate this hypothesis into a different schemata where there are two levels of control of cell growth. The paracrine hypothesis describes a situation where tumours are dependent upon the secretion of a distant factor for their growth and this is exemplified by the dependence of some breast tumours upon oestrogenic steroids. An alternative scenario involves the regulation of tumours by locally secreted growth factors and this is the autocrine hypothesis, examples of which may include transforming growth factors and gonadotrophin releasing hormone like factors in breast and prostatic cancer. This article describes the role of paracrine and autocrine factors in the control of hormone dependent malignancy.

Female↗
PubMed1991

Reactive arthritis due to hidradenitis suppurativa mimicking osteomyelitis.

We have reported a case of erosive arthritis of the hand preceding the appearance of hidradenitis suppurativa in the ipsilateral axilla, which was mistaken for osteomyelitis. Recognition of this presentation is important to avoid unnecessary invasive diagnostic procedures and to initiate prompt treatment directed at the underlying cause.

Arthritis, Infectious↗
PubMed1990

The partial purification and characterization of GnRH-like activity from prostatic biopsy specimens and prostatic cancer cell lines.

We have investigated the possibility of the secretion of gonadotrophin-releasing-hormone (GnRH)-like peptides by prostatic cancer cells in culture and their presence in cytosolic preparations from human prostatic biopsy specimens. A GnRH-specific radioimmunoassay showed GnRH-like activity in concentrated cytosolic preparations and conditioned media from DU 145, an androgen-insensitive human prostatic cell line and from LNCaP, an androgen-responsive prostatic cancer cell line. GnRH immunoreactivity in culture media correlated directly with cell numbers. HPLC demonstrated that this GnRH-like material co-migrated with synthetic GnRH. This homology between synthetic GnRH and partially purified prostatic GnRH was confirmed following V8 protease and trypsin digestion which resulted in similar alterations in HPLC characteristics. The mean content of GnRH-like activity/g specimen tissue was significantly more in malignant tissue (88.5 +/- 80.5 fmol) than in benign (29.6 +/- 22 fmol), though more specimens of benign tissue were positive (37/54) than malignant tissue (6/22). This observation, taken with an earlier finding of GnRH-specific receptors in a hormone-sensitive cell line and human cancer specimens provides supportive evidence for the autocrine hypothesis of cell regulation.

Gonadotropin-Releasing Hormone↗
PubMed1990

Effects of chemotherapy on fertility.

Over recent years radical improvements in the treatment of malignant disease have resulted in the cure of patients in or approaching reproductive age, and with that cure, the effects on gonadal function have become apparent. Gonadal failure is particularly important in Hodgkin's disease, germ cell tumours, choriocarcinoma, and leukaemia, diseases of young people which are largely curable. Premature ovarian and testicular failure are easily missed by doctors concerned primarily with the erradication or arrest of a life-threatening disease, but for the patient the hormonal, psychological and social sequelae of treatment may be devastating. In this article we review the effects of chemotherapy on gonadal function and discuss the management of gonadal failure.

Antineoplastic Agents↗