Multidrug resistant gastrointestinal stromal tumor with multiple metastases to the skin and subcutaneous soft tissue: A case report and review of literature

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms which account for less than 1% of all gastrointestinal malignancies. Of all the extra-abdominal metastases of GIST, superficial soft tissue metastases are the rarest. Previous reports have found success with sunitinib in imatinib-resistant GIST, but we report a certain wild-type KIT mutation GIST with cutaneous and subcutaneous metastasis that was unresponsive to multiple tyrosine kinase inhibitor (TKI) treatments. This case illustrates that knowing the specific type of KIT mutations may uncover resistance of certain GIST's to TKIs, necessitating more targeted and alternative therapy.     

Effect of methotrexate on protein and amylase secretion by rat parotid and submandibular salivary glands

Saliva was collected from anaesthetized, methotrexate (MTX)-treated, pair-fed and control rats using either acetylcholine or bethanechol as secretagogue. Parotid saliva was analysed for protein and amylase content, and submandibular saliva for protein. Acetylcholine stimulation after MTX increased parotid protein output by 151 per cent, amylase output by 125 per cent and submandibular protein output by 229 per cent when compared to control values. There were no significant differences in either protein or amylase output between the control and pair-fed animals. With bethanechol, salivary amylase and protein secretion did not differ between MTX-treated and control animals. The significant increase in parotid protein and amylase output with acetylcholine was reduced by pretreatment with hexamethonium (5 mg/kg) or propranolol (5 mg/kg), but not by phenoxybenzamine (1 mg/kg). MTX did not increase the number or the dissociation constant of parotid beta-adrenergic receptors but did increase their number in the submandibular gland. Thus increases in protein and amylase output caused by acetylcholine MTX-treated rats may be the result of increased beta-adrenergic activity.