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Biomedical subjects

J Waxman

Publications and source records attributed to J Waxman.

At least 109 records · Page 6Linked to original sources
PubMed1990

The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors.

We have investigated the possibility of a direct regulatory effect of gonadotrophin releasing hormone (GnRH) analogues on prostatic cancer cell growth. Here we report high affinity binding (Kd = 50 nM) of a GnRH analogue resulting in biphasic growth modulation of the human androgen-sensitive prostatic cancer cell line LNCaP. In contrast, the human androgen-insensitive prostatic cancer cell line DU145 showed low-affinity (Kd = 10 microM) binding without any biological response to the GnRH analogue. A GnRH-specific radioimmunoassay demonstrated GnRH-like immunoreactivity in the concentrated culture medium from both cell lines. Seventy-six human benign and malignant tumours were assayed following surgical resection. Nineteen of 22 (86%) malignant tumours and 49 of 54 (91%) benign tumours, exhibited high affinity GnRH-analogue binding. Fourteen of 19 (74%) malignant tumours and 17 of 49 (35%) benign tumours exhibiting high affinity binding contained GnRH-like immunoreactivity, suggesting that this system may be involved in prostatic epithelial cell growth in vivo.

Buserelin↗
PubMed1990

Three-monthly GnRH agonist (buserelin) for prostatic cancer.

A new slow release formulation of buserelin given as a 3-monthly depot injection has been evaluated in 4 patients with advanced prostatic cancer previously maintained on shorter acting depots. Treatment was maintained for a mean period of 21 months. Steady state urinary buserelin concentrations were reached by the beginning of the third treatment week and maintained until the end of the third treatment month. Serum testosterone remained suppressed in the castrate range for the duration of the study. Seven previously untreated patients were entered into treatment. Serum testosterone was suppressed into the castrate range between the seventh and fourteenth days after implantation. This preparation offers an advantage for the patient and clinician over existing methods of GnRH analogue administration and will now enter further clinical trial.

Buserelin↗
PubMed1989

A pharmacological evaluation of a new 3-month depot preparation of buserelin for prostatic cancer.

A new slow-release formulation of buserelin given as a 3-month depot injection was evaluated in four patients with advanced prostatic cancer. Treatment was maintained for a mean period of 15 months. Steady-state urinary buserelin concentrations were reached by the beginning of the 3rd week of treatment and maintained until the end of the 3rd month. Serum testosterone remained suppressed in the castrate range for the duration of the study. This preparation offers an advantage for the patient and clinician over existing methods of gonadotrophin-releasing hormone (GnRH) analogue administration and will enter further clinical trial.

Buserelin↗
PubMed1989

c-myc oncogene expression and clinical outcome in carcinoma of the cervix.

The expression of the c-myc oncogene was studied in paraffin-embedded specimens of cervical biopsies using a monoclonal antibody which binds to the 62,000 Dalton protein encoded by the c-myc gene. A range of cervical cancers from intraepithelial neoplasia to advanced grade IV tumours were studied together with normal cervical biopsies; c-myc status was correlated to clinical progress. There was no correlation seen between the clinical stage of the disease at presentation and c-myc expression. The 15 patients with c-myc negative cervical cancers were shown to have better disease free (mean--95.4 mos) and total survival (mean 118.0--mos) compared to the 16 patients that were c-myc positive 28.4 and 48.4 mos respectively). The pattern of recurrence differed between the two groups with c-myc positive tumours more likely to develop extra pelvic metastatic disease. The c-myc status of cervical cancer offers a prognostic indicator that could be useful in guiding treatment decisions.

Female↗
PubMed1989

The treatment of essential thrombocythaemia with radioactive phosphorus.

The major complications of essential thrombocythaemia include haemorrhage and thrombosis, events which are related to the level of the abnormal platelet count. We report here on the use of radioactive phosphorus (32P) in eight patients with essential thrombocythaemia. Two patients required multiple injections of 32P to control platelet count, and there was no reduction in the rate of fall of platelets with each injection. Three patients required chemotherapy for persistent thrombocythaemia despite multiple doses of 32P. No clinical or haematological characteristics could be identified for those patients whose disease was difficult to control. Radioactive phosphorus is a safe and effective method to control platelet counts in patients with essential thrombocythaemia.

Adult↗
PubMed1989

Oncogene expression in cholangiocarcinoma and in normal hepatic development.

The expression of the proteins encoded by the ras, myc, and erb B-2 oncogenes was examined in 63 paraffin-embedded human cholangiocarcinomas of Thai and English origin using immunohistochemistry. The observed distributions were compared with oncogene expression in a series of human hepatocellular carcinomas. In an attempt to relate expression of these three oncogenes to specific stages of normal tissue differentiation, tissue sections of normal fetal, infant, and adult human livers were also examined. Of 63 cholangiocarcinomas, 59 (95%) expressed p62 c-myc, 47 (75%) expressed p21 c-ras, and 46 (73%) expressed p190 c-erbB-2. The expression of c-myc and c-ras but not of c-erb B-2 correlated directly with tumor differentiation as judged by morphologic criteria. No difference was observed in oncogene expression between intrahepatic and extrahepatic cholangiocarcinomas. Twelve of 14 hepatocellular carcinomas (86%) stained positively for all three oncoproteins. During normal liver development, expression of c-myc and c-ras was shown to occur from 18 weeks' gestation until 5 years of age, but not thereafter. Expression of c-myc, c-ras, and c-erbB-2 oncogenes may be used as immunohistochemical markers to distinguish cholangiocarcinoma from nonneoplastic biliary tissues, and may provide useful information concerning the cell biology of tumor differentiation.

Adenoma, Bile Duct↗
PubMed1989

New combination chemotherapy programme for bladder cancer.

Forty patients with either metastatic, post-radiotherapy recurrent, or poor prognosis locally advanced transitional cell carcinoma of the bladder were treated in a new combination chemotherapy programme with methotrexate, vinblastine, mitozantrone and JM8 (carboplatin); 33 patients were assessable for response. There were 9 complete responses (27%), 12 partial responses (36%) and 7 disease stabilizations (21%); 5 patients (15%) had progressive disease. The median duration of complete response has not been reached and is in excess of 9 months (range 4- greater than 18 months). This regimen was without significant toxicity and this is in contrast with M-VAC, which is thought to be currently the most effective treatment for urothelial cancer.

Adult↗
PubMed1989

Prostatic complications of testosterone replacement therapy.

The prostatic complications of testosterone replacement therapy have received little clinical attention. We describe three hypogonadal men who had prostatic disease (adenocarcinoma in two) detected in relation to such therapy. Literature review suggests that surveillance for early prostate cancer is appropriate during replacement therapy in men over the age of 50 years. We discuss the selective use of digital rectal examination, transrectal sonography, directed prostate biopsy, and prostate-specific antigen determinations before therapy and in subsequent follow-up in this age group of men during androgen replacement.

Aged↗
PubMed1989

Congenital heart block in successive pregnancies: a case report and evaluation of risk with therapeutic consideration.

SS-A antibody has been found to bind to fetal cardiac tissue and is thought to mediate congenital heart block via transplacental passage. Recent papers have identified various risk factors thought to define subclasses of SS-A antibody-positive mothers at greater risk of delivering children with congenital heart block. Treatment modalities for antibody-mediated fetal insult are now expanding and being used clinically. We report a case of a clinically asymptomatic SS-A antibody-producing mother who gave birth to two SS-A antibody-positive children with congenital heart block. It is our hope that ongoing refinement of risk factors and effective therapy will result in successful in utero palliation of the effects of SS-A antibody.

Adult↗
PubMed1988

The clinical and endocrine assessment of three different antiandrogen regimens combined with a very long-acting gonadotrophin-releasing hormone analogue.

Tumor flare is reported in up to 40% of patients treated with gonadotrophin-releasing hormone analogues for prostate cancer. In order to investigate the optimal way to eliminate tumor flare, we have treated patients with one of three different antiandrogen regimens used in combination with gonadotrophin-releasing hormone (GnRH) agonist. The early results of this study are presented here. Thirty patients with advanced symptomatic disease were randomized to receive either cyproterone acetate 50 or 100 mg three times daily or flutamide 250 mg three times daily given for 1 week before and during the first month of GnRH agonist treatment. The endocrine profiles of these patients were compared with those of historic controls treated with depot agonist alone. Three patients treated with low-dose cyproterone acetate and one with flutamide developed a transient exacerbation of their disease. No patients treated with the higher-dose cyproterone acetate regimen developed tumor flare. No patients treated with cyproterone acetate had an increase in serum testosterone above baseline following depot GnRH agonist implantation. All patients treated with flutamide had increases in serum testosterone, but this did not significantly increase further with implantation. This study suggests that all patients receiving GnRH agonist treatment should be pretreated with cyproterone acetate 100 mg three times daily for 1 week before implantation and for the first treatment month.

Aged↗