neurokinin-a and Neoplasm-Metastasis

Assessing prognosis is important in patients with neuroendocrine tumours of the small bowel as disease progression and survival is variable. We previously identified raised Neurokinin A as an independent indicator of poor prognosis and have shown that prognosis worsens when circulating Neurokinin A rises ≥50 ng/L. In the present study we have examined survival in relation to Neurokinin A concentrations.. Patients in whom Neurokinin A rose ≥50 ng/L between January 1989 and December 2010 were identified. All circulating Neurokinin A concentrations were recorded and survival was followed up to 31 December 2014 or to death.. Median survival, from the date when Neurokinin A was first ≥50 ng/L was 11.1 (2.0-117.8) months if Neurokinin A remained ≥50 ng/L and 72.4 (4.8-152.6) months when Neurokinin A was reduced below 50 ng/L and controlled below that concentration for ≥3 months (P < 0.001). Survival was significantly better for patients attending the neuroendocrine tumour specialist clinic than for those not attending (P = 0.009). Comparing patients identified during 1989-2000, and those during 2001-2010, Neurokinin A was successfully reduced in the earlier period in 30.3% patients with median survival 23.2 (2.0-152.6) months and this improved in 58.1% with median survival of 43.3 (2.0-141.1) months in the later period (P = 0.019). Significance was greater between the earlier and later periods when only patients attending the neuroendocrine tumour clinic were compared (P = 0.016).. Circulating Neurokinin A ≥ 50 ng/L is a strong indicator of poor prognosis when Neurokinin A remains above this concentration. Lowering Neurokinin A below 50 ng/L indicates a significant improvement in prognosis (P < 0.001). This prognostic indicator reflects improved treatment and survival in more recent years.

Topics: Biomarkers, Tumor; Humans; Intestinal Neoplasms; Intestine, Small; Neoplasm Metastasis; Neuroendocrine Tumors; Neurokinin A; Prognosis; Radioimmunoassay; Survival Analysis

Cutaneous flushing was provoked in seven patients with metastatic carcinoid tumours and the carcinoid syndrome by an intravenous injection of pentagastrin (0.6 micrograms.kg-1 body weight). The patients were studied before and 1 h after a subcutaneous injection of the long-acting somatostatin analogue octreotide 50 micrograms (Sandostatin). The severity of the carcinoid flush in all the patients was reduced by administration of the analogue. The rise in facial temperature was 1.3 (0.3) degree C before and 0.8 (0.2) degree C after octreotide. Six patients responded to pentagastrin with a rise in the circulating neurokinin A-like immunoreactivity (NKA-LI) and five patients with a rise in circulating substance P-like immunoreactivity (SP-LI). No cutaneous flushing or rise in tachykinin concentration was observed in healthy subjects (n = 6) after injection of pentagastrin. The rise in NKA-LI in the patients was decreased by 61 (14)% and the rise in SP-LI by 54 (13)% after octreotide. Although flushing still occurred, the tachykinin response in two patients was completely abolished. The data demonstrate that the release of tachykinins from carcinoid tumours during pentagastrin-induced flushing is subject to partial inhibition by octreotide. However, the occurrence of a flush in some patients in the absence of a detectable rise in circulating tachykinins indicates that the latter peptides cannot be the sole causative agent of the carcinoid flush.

Topics: Aged; Body Temperature; Carcinoid Tumor; Female; Flushing; Humans; Ileal Neoplasms; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neurokinin A; Octreotide; Pentagastrin; Radioimmunoassay; Substance P; Tachykinins

Using an antiserum directed at the COOH-terminus of tachykinins, we have examined postmortem tissue from two cases of metastatic ileal carcinoid for the presence of tachykinin-like immunoreactivity. The vast majority of the immunoreactive tachykinin-like material eluted from a Sephadex G-50 column as two peaks at positions corresponding to molecular weights of 1300 and 850. The 1300 dalton peak was resolved by reverse-phase-HPLC into two components which by Edman sequencing, amino acid analysis, and fast atom bombardment (FAB)-mass spectrometry criteria, were identified as substance P and substance K. The 850 dalton peak was also resolved on RP-HPLC into two peaks which were resistant to Edman degradation but from amino acid analysis and FAB-mass spectrometry criteria were identified as pyro-Glu-substance P 5-11 and oxidized pyro-Glu-substance P 5-11. In control experiments substance P 5-11 was converted to pyro-Glu-substance P 5-11 during the extraction procedure. Both tumors also contained a minor immunoreactive peak which eluted from a Sephadex G-50 sizing column at a position corresponding to a molecular weight of 4000 which probably represents neuropeptide K. These results suggest that beta-preprotachykinin is preferentially expressed in carcinoid tumors and that substance K may also play a role in the carcinoid syndrome.

Topics: Amino Acid Sequence; Carcinoid Tumor; Chromatography, High Pressure Liquid; Humans; Ileal Neoplasms; Mass Spectrometry; Neoplasm Metastasis; Nerve Tissue Proteins; Neurokinin A; Peptide Fragments; Substance P; Tachykinins