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Biomedical subjects

A Qayum

Publications and source records attributed to A Qayum.

15 recordsLinked to original sources
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↗
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

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↗
PubMed1979

Effects of noradrenaline and metaraminol on isolated aortic strips and auricles obtained from untreated and reserpine-treated rabbits.

The isolated aortic strips of the untreated rabbits responded to noradrenaline in concentrations ranging from 20 to 160 ng/mL, whereas similar preparations from reserpine-treated animals responded to lower concentrations (from 2.5 to 10 ng/mL) and larger effects were produced by concentrations ranging from 20 to 160 ng/mL. Comparatively stronger concentrations (from 0.4 to 1.6 microgram/mL) of metaraminol were required to produce suitable contractile responses, which were not modified by reserpine pretreatment. On the isolated auricles obtained from untreated rabbits, noradrenaline was used in concentrations of 20 and 80 ng/mL, but these concentrations were reduced to 2.5 and 10 ngmL in the case of tissues obtained from reserpinized rabbits. Comparatively stronger (0.2 and 0.8 microgram/mL) concentrations of metaraminol were required to produce a stimulant effect on this preparation, and the sensitivity was not altered by reserpine pretreatment. These observations lead to the conclusions that though reserpine pretreatment produces a well-marked increase in the sensitivity of isolated rabbit aortic strips and auricles to noradrenaline, it does not modify the sensitivity of these preparations to metaraminol. Reserpine was used in 0.3 mg/kg doses injected subcutaneously for 3 successive days.

Animals↗