1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108.

2. Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin 2014;64:104-17.

3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.

4. Modjtahedi H, Essapen S. Epidermal growth factor receptor inhibitors in cancer treatment: advances, challenges and opportunities. Anticancer Drugs 2009;20:851-5.

5. Overman MJ, Hoff PM. EGFR-targeted therapies in colorectal cancer. Dis Colon Rectum 2007;50:1259-70.

6. Ilyas M. Wnt signalling and the mechanistic basis of tumour development. J Pathol 2005;205:130-44.

7. Wess J. Molecular biology of muscarinic acetylcholine receptors. Crit Rev Neurobiol 1996;10:69-99.

8. Wess J. Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications. Annu Rev Pharmacol Toxicol 2004;44:423-50.

9. Shah N, Khurana S, Cheng K, Raufman JP. Muscarinic receptors and ligands in cancer. Am J Physiol Cell Physiol 2009;296:C221-32.

10. Spindel ER. Muscarinic receptor agonists and antagonists: effects on cancer. Handb Exp Pharmacol 2012;208:451-68.

11. Spindel ER. Cholinergic targets in lung cancer. Curr Pharm Des 2016;22:2152-9.

12. Kruse AC, Kobilka BK, Gautam D, Sexton PM, Christopoulos A, Wess J. Muscarinic acetylcholine receptors: novel opportunities for drug development. Nat Rev Drug Discov 2014;13:549-60.

13. Frucht H, Gazdar AF, Park JA, Oie H, Jensen RT. Characterization of functional receptors for gastrointestinal hormones on human colon cancer cells. Cancer Res 1992;52:1114-22.

14. Frucht H, Jensen RT, Dexter D, Yang WL, Xiao Y. Human colon cancer cell proliferation mediated by the M3 muscarinic cholinergic receptor. Clin Cancer Res 1999;5:2532-9.

15. Yang WL, Frucht H. Cholinergic receptor up-regulates COX-2 expression and prostaglandin E(2) production in colon cancer cells. Carcinogenesis 2000;21:1789-93.

16. Grando SA. Biological functions of keratinocyte cholinergic receptors. J Investig Dermatol Symp Proc 1997;2:41-8.

17. Schlereth T, Birklein F, an Haack K, Schiffmann S, Kilbinger H, Kirkpatrick CJ, Wessler I. in vivo release of non-neuronal acetylcholine from the human skin as measured by dermal microdialysis: effect of botulinum toxin. Br J Pharmacol 2006;147:183-7.

18. Song P, Sekhon HS, Jia Y, Keller JA, Blusztajn JK, Mark GP, Spindel ER. Acetylcholine is synthesized by and acts as an autocrine growth factor for small cell lung carcinoma. Cancer Res 2003;63:214-21.

19. Tsuji S, Anglade P. Acetylcholine in neurons and paraneurons: a histochemical study. Arch Histol Cytol 1989;52:75-83.

20. Keely SJ. Epithelial acetylcholine -- a new paradigm for cholinergic regulation of intestinal fluid and electrolyte transport. J Physiol 2011;589:771-2.

21. Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 2011;334:98-101.

22. Brandon EP, Lin W, D'Amour KA, Pizzo DP, Dominguez B, Sugiura Y, Thode S, Ko CP, Thal LJ, Gage FH, Lee KF. Aberrant patterning of neuromuscular synapses in choline acetyltransferase-deficient mice. J Neurosci 2003;23:539-49.

23. Klapproth H, Reinheimer T, Metzen J, Münch M, Bittinger F, Kirkpatrick CJ, Höhle KD, Schemann M, Racké K, Wessler I. Non-neuronal acetylcholine, a signalling molecule synthezised by surface cells of rat and man. Naunyn Schmiedebergs Arch Pharmacol 1997;355:515-23.

24. Cheng K, Samimi R, Xie G, Shant J, Drachenberg C, Wade M, Davis RJ, Nomikos G, Raufman JP. Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation. Am J Physiol Gastrointest Liver Physiol 2008;295:G591-7.

25. von Rosenvinge EC, Cheng K, Drachenberg CB, Fowler CB, Evers DL, Xie G, Raufman JP. Bedside to bench: role of muscarinic receptor activation in ultrarapid growth of colorectal cancer in a patient with pheochromocytoma. Mayo Clin Proc 2013;88:1340-6.

26. Raufman JP, Zimniak P, Bartoszko-Malik A. Lithocholyltaurine interacts with cholinergic receptors on dispersed chief cells from guinea pig stomach. Am J Physiol 1998;274:G997-1004.

27. Raufman JP, Chen Y, Cheng K, Compadre C, Compadre L, Zimniak P. Selective interaction of bile acids with muscarinic receptors: a case of molecular mimicry. Eur J Pharmacol 2002;457:77-84.

28. Cheng K, Khurana S, Chen Y, Kennedy RH, Zimniak P, Raufman JP. Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther 2002;303:29-35.

29. Cheng K, Chen Y, Zimniak P, Raufman JP, Xiao Y, Frucht H. Functional interaction of lithocholic acid conjugates with M3 muscarinic receptors on a human colon cancer cell line. Biochim Biophys Acta 2002;1588:48-55.

30. Cheng K, Raufman JP. Bile acid-induced proliferation of a human colon cancer cell line is mediated by transactivation of epidermal growth factor receptors. Biochem Pharmacol 2005;70:1035-47.

31. Cheng K, Zimniak P, Raufman JP. Transactivation of the epidermal growth factor receptor mediates cholinergic agonist-induced proliferation of H508 human colon cancer cells. Cancer Res 2003;63:6744-50.

32. Raufman JP, Chen Y, Zimniak P, Cheng K. Deoxycholic acid conjugates are muscarinic cholinergic receptor antagonists. Pharmacology 2002;65:215-21.

33. Cheng K, Xie G, Raufman JP. Matrix metalloproteinase-7-catalyzed release of HB-EGF mediates deoxycholyltaurine-induced proliferation of a human colon cancer cell line. Biochem Pharmacol 2007;73:1001-12.

34. Hamilton JP, Xie G, Raufman JP, Hogan S, Griffin TL, Packard CA, Chatfield DA, Hagey LR, Steinbach JH, Hofmann AF. Human cecal bile acids: concentration and spectrum. Am J Physiol Gastrointest Liver Physiol 2007;293:G256-63.

35. Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, Ganiats T, Levin T, Woolf S, Johnson D, Kirk L, Litin S, Simmang C; Gastrointestinal Consortium Panel. Colorectal cancer screening and surveillance: clinical guidelines and rationale-update based on new evidence. Gastroenterology 2003;124:544-60.

36. Soler AP, Miller RD, Laughlin KV, Carp NZ, Klurfeld DM, Mullin JM. Increased tight junctional permeability is associated with the development of colon cancer. Carcinogenesis 1999;20:1425-31.

37. Flynn C, Montrose DC, Swank DL, Nakanishi M, Ilsley JN, Rosenberg DW. Deoxycholic acid promotes the growth of colonic aberrant crypt foci. Mol Carcinog 2007;46:60-70.

38. Dawson PA, Haywood J, Craddock AL, Wilson M, Tietjen M, Kluckman K, Maeda N, Parks JS. Targeted deletion of the ileal bile acid transporter eliminates enterohepatic cycling of bile acids in mice. J Biol Chem 2003;278:33920-7.

39. Raufman JP, Dawson PA, Rao A, Drachenberg CB, Heath J, Shang AC, Hu S, Zhan M, Polli JE, Cheng K. Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids. Carcinogenesis 2015;36:1193-200.

40. Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183-232.

41. Ozğul C, Karaöz E, Erdoğan D, Dursun A. Expression of epidermal growth factor receptor in normal colonic mucosa and in adenocarcinomas of the colon. Acta Physiol Hung 1997;85:121-8.

42. Xie G, Cheng K, Shant J, Raufman JP. Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells. Am J Physiol Gastrointest Liver Physiol 2009;296:G755-63.

43. Raufman JP, Samimi R, Shah N, Khurana S, Shant J, Drachenberg C, Xie G, Wess J, Cheng K. Genetic ablation of M3 muscarinic receptors attenuates murine colon epithelial cell proliferation and neoplasia. Cancer Res 2008;68:3573-8.

44. Raufman JP, Shant J, Xie G, Cheng K, Gao XM, Shiu B, Shah N, Drachenberg CB, Heath J, Wess J, Khurana S. Muscarinic receptor subtype-3 gene ablation and scopolamine butylbromide treatment attenuate small intestinal neoplasia in Apcmin/+ mice. Carcinogenesis 2011;32:1396-402.

45. Cheng K, Xie G, Khurana S, Heath J, Drachenberg CB, Timmons J, Shah N, Raufman JP. Divergent effects of muscarinic receptor subtype gene ablation on murine colon tumorigenesis reveals association of M3R and zinc finger protein 277 expression in colon neoplasia. Mol Cancer 2014;13:77.

46. Peng Z, Heath J, Drachenberg C, Raufman JP, Xie G. Cholinergic muscarinic receptor activation augments murine intestinal epithelial cell proliferation and tumorigenesis. BMC Cancer 2013;13:204.

47. Belo A, Cheng K, Chahdi A, Shant J, Xie G, Khurana S, Raufman JP. Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion. Am J Physiol Gastrointest Liver Physiol 2011;300:G749-60.

48. Raufman JP, Cheng K, Saxena N, Chahdi A, Belo A, Khurana S, Xie G. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells. Biochem Biophys Res Commun 2011;415:319-24.

49. Philip AK, Philip B. Colon targeted drug delivery systems: a review on primary and novel approaches. Oman Med J 2010;25:79-87.

Journal of Cancer Metastasis and Treatment
ISSN 2454-2857 (Online) 2394-4722 (Print)


All published articles are preserved here permanently:


All published articles are preserved here permanently: