Link discovered between MEN1 and much-studied Hedgehog signal pathway

Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome
-Xianxin Hua, MD, PhD, Buddha Gurung, PhD, Perelman School of Medicine, University of Pennsylvania
Cancer Research April 15, 2013 73:2650-2658; Published OnlineFirst April 15, 2013;

Link discovered between MEN1 and much-studied cell pathway
A research team led by Xianxin Hua, MD, PhD, associate professor of Cancer Biology at the Abramson Family Cancer Research Institute, report in Cancer Research that menin suppresses signaling in the much-studied Hedgehog pathway in endocrine organs.

• "This study uncovered a new layer of regulation of pro-proliferative genes by menin via the Hedgehog signaling pathway," Hua says.
  
• "These pro-replication genes are regulated through GAS1 and PRMT5."
  
• The GAS1 protein promotes Hedgehog signaling.
  
• Menin interacts with the methylating enzyme PRMT5, and binds to the promoter of the Gas1 gene, inhibiting Gas1 gene transcription.
  
• By inhibiting Gas1 expression, menin and PRMT5 inhibit the pathway's tendency towards cell proliferation.
  
• Mutant menin proteins are impaired in their ability to interact with PRMT5, and lead to increased Hedgehog signaling and cell proliferation.
  
• Hua's team found that treating a mouse model of human MEN1 with a Hedgehog pathway inhibitor called Erivedge reduced proliferation of tumor cells and blood insulin levels. Hua says that this suggests a potential new treatment for MEN1 patients.
  

Men1 mouse studies claim pre-clinical proof-of-concept for gene replacement therapy in pituitary NETs.

Clinical and pre-clinical studies of neuroendocrine tumours (NETs) in multiple endocrine neoplasia type 1 (MEN1), and evaluation of MEN1 gene replacement therapy for MEN1-associated NETs.
-Gerard Walls, Paul Newey, et al.
Endocrine Abstracts (2013) 31 YEP1.1 | DOI:10.1530/endoabs.31.YEP1.1

Hyperprolactinemia and Macroprolactinemia

Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays.
-B Cavaco, S Prazeres, et al.
J Endocrinol Invest. 1999 Mar;22(3):203-8.

"Macroprolactinemia, i.e. sustained hyperprolactinemia where the predominant circulating form of prolactin (PRL) is of large molecular weight, is a common phenomenon comprising up to one-fourth of all cases of hyperprolactinemia."

"we suggest that the routine measurement of PRL should be done with methods that are only minimally affected by the presence of macroprolactin."

Hyperprolactinemia or pseudohyperprolactinemia?

Reporting of Post–PEG Prolactin Concentrations: Time to Change
-T Smith, M Fahie-Wilson
Clinical Chemistry March 2010 vol. 56 no. 3 484-485

Measurement of serum prolactin levels can be exagerated by the presence of biologically inactive "big prolactin" or "macroprolactin", aka "big big prolactin".

"The polyethylene glycol (PEG) precipitation test is widely used to detect pseudohyperprolactinemia caused by big prolactin and/or macroprolactin. Current best practice recommends that all sera with increased total prolactin concentrations be subfractionated by PEG precipitation to measure the bioactive monomeric prolactin concentration, a more clinically meaningful variable."

MEN1 -overview and treatment

Multiple endocrine neoplasia type 1 (MEN1)
-Richard W. Carroll
Asia-Pacific Journal of Clinical Oncology,Wiley Online Library, 2012
doi: 10.1111/ajco.12046

DCA (dichloroacetic acid) - a possible future cancer treatment?

Dichloroacetic acid - Wikipedia, the free encyclopedia

There are wild rumors that DCA (dichloroacetic acid) "cures" cancer. Ignoring what seem to be premature and extreme claims, the facts about DCA are interesting to consider. Perhaps DCA may have a future in cancer treatment.

Genetic and Clinical Features of Multiple Endocrine Neoplasia Types 1 and 2

Genetic and Clinical Features of Multiple Endocrine Neoplasia Types 1 and 2

-C. Romei, et al.
Journal of Oncology, Volume 2012, Article ID 705036