Lutetium in the treatment of neuroendocrine tumours

Lutetium-labelled peptides for therapy of neuroendocrine tumours

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304065

Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with 177Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). 

Menin -today's growth promoter, tomorrow's tumor suppressor

Elucidating the Role of Menin During Islet Cell Development in the Human Fetal Pancreas
-Dubrick, Jessica L., (2013).  
University of Western Ontario - Electronic Thesis and Dissertation Repository. Paper 1287.
http://ir.lib.uwo.ca/etd/1287

editor's notes:

Menin functions as a tumor suppressor in adult endocrine cells, but in the fetal pancreas promotes cell survival and proliferation.  At first glance these roles seem very different, almost opposite.  But are they really opposed?

If menin promotes the proliferation of healthy pancreas cells -in particular, cells with at least one functional MEN1 gene- then it would seem that these cells will proliferate faster than those unable to produce menin.  So, cells that are unable to produce menin will represent a decreasing fraction of the cell population. Therefore, even during fetal development, menin's role as a growth promoter offers a tumor suppressive advantage to the developing pancreas, by reducing the percentage of cells that later may pose a tumorigenic risk due to their inability to express menin.

Unless I've got that wrong.

The MEN 1 Pancreas: Tumor Development and Haploinsufficiency

The MEN 1 Pancreas: Tumor Development and Haploinsufficiency

-H Lejonklou, et al.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206; 792. ISBN 978-91-554-8415-6.

• A collection of four papers on MEN1 and PNET (pancreatic neuroendocrine tumors).
  

Testing Of New Drug For Patients With Neuroendocrine Tumors

Testing Of New Drug For Patients With Neuroendocrine Tumors

• "Pasireotide is a novel multireceptor-targeted somatostatin analogue that binds to four of the five known somatostatin receptor subtypes... Because of its binding ability, it may offer symptom reduction for patients who have eventually failed to respond to traditional therapy."
  
• The multicenter clinical trial, conducted at sites in the United States and Europe, enrolled 89 patients and evaluated 44 for efficacy and 45 for tolerability. Pasireotide "effectively controlled symptoms." Evaluation of tumor response in 23 patients showed 13 with stable disease and 10 with progressive disease. The drug was "effective and well-tolerated" and adverse events, most commonly gastrointestinal, were "mild or moderately severe."
  
• A Phase III study evaluating pasireotide versus octreotide is ongoing for patients with advanced NET whose disease-related symptoms have been inadequately controlled.
  
  

What Extent of Pancreatic Resection Do Patients with MEN-1 Require?

What Extent of Pancreatic Resection Do Patients with MEN-1 Require?
-C. D. Adkisson, et al.
JOP. J Pancreas (Online) 2012 Jul 10; 13(4):402-408.

• "In patients with MEN-1 and pancreatic endocrine tumors, preoperative workup underestimates extent of disease and total pancreatectomy should be considered for complete tumor removal."
  

Genome-Wide Characterization of Menin-Dependent H3K4me3 Reveals a Specific Role for Menin

Genome-Wide Characterization of Menin-Dependent H3K4me3 Reveals a Specific Role for Menin in the Regulation of Genes Implicated in MEN1-Like Tumors
-S Agarwal, R Jothi
PLoS ONE 7(5): e37952. doi:10.1371/journal.pone.0037952

Temozolomide therapy in a man with an aggressive prolactin-secreting pituitary neoplasm: Morphological findings

Temozolomide therapy in a man with an aggressive prolactin-secreting pituitary neoplasm: Morphological findings
-Kovacs K, et al. Human Pathology Volume 38, Issue 1 , Pages 185-189, January 2007

• "Based on the clinical, laboratory, and morphological findings, we recommend temozolomide therapy in patients with pituitary tumors not responding adequately to other treatment options."

Prolactinomas: Diagnosis and Treatment: Management

Prolactinomas: Diagnosis and Treatment: Management
-Nassiri F, et al. Medscape Education CME Released: 02/29/2012.

• "Despite the effectiveness of [dopamine agonists]... some [patients] do not respond at therapeutic levels or higher. Such patients are considered to be DA resistant. The mechanism of resistance seems to be mediated by a decreased number of D2 receptors without a decreased affinity for DA agonists, and an altered signal transduction mechanism."
• "In resistant patients, treatment options include switching DA agonists, increasing DA agonist dosage beyond convention and surgery and/or radiotherapy."
• "Although doses of 2 mg/week exceed recommended package levels for cabergoline, some patients may require up to 3 mg/day for normalization of PRL levels."
• "Temozolomide therapy has even reduced tumor volume and normalized PRL levels in a resistant macroprolactinoma suggesting a possible role for temozolomide in resistant prolactinomas."

Asymptomatic children with multiple endocrine neoplasia type 1 (MEN1) mutations harbour pancreatic and pituitary tumours

Asymptomatic children with multiple endocrine neoplasia type 1 (MEN1) mutations harbour pancreatic and pituitary tumours
-Newey P, et al. Endocrine Abstracts (2009) 19 P171

• "...These two cases highlight the importance of screening children with MEN1 mutations as early diagnosis and treatment is likely to reduce both morbidity and mortality."

MEN1 and pituitary adenomas

MEN1 and pituitary adenomas
-Delemer B. Service d’endocrinologie-diabète-nutrition

"MEN1 [pituitary] tumors seem more aggressive, invasive and resistant to treatment requiring a very careful long-life follow-up. Occurrence of these tumors can be described in the pediatric population and it can be the first and only manifestation of MEN1 for some years asking the question of the systematic screening for MEN1 gene mutation in pediatric population with pituitary adenoma."

Pituitary tumors in patients with MEN1 syndrome

Pituitary tumors in patients with MEN1 syndrome
-Syro LV, et al. Copyright © 2012 Hospital das Clínicas da FMUSP

• "pituitary tumors in MEN1 ...are more often resistant to medical therapy."
• "...normalization of pituitary hypersecretion was much less frequent in MEN1 patients than in non-MEN1 subjects (42% vs. 90%)."

Endoscopic Removal of Pituitary Tumors

Endoscopic transphenoidal resection of pituitary tumors at UCLA.