Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A middle-aged female patient, previously diagnosed with asthma, presented with a large spontaneous left pneumothorax. She had a history of nephrectomy for a ruptured renal angiomyolipoma (AML) with a postoperative spontaneous pneumothorax when she was an adolescent. High-resolution CT chest revealed multiple scattered thin-walled lung parenchyma cysts consistent with lymphangioleiomyomatosis (LAM). Hepatic AMLs and adenoma sebaceum skin lesions were also noted, consistent with an overall diagnosis of tuberous sclerosis. Her acute management included lung re-expansion via chest tube insertion, antibiotics for concurrent chest infection, nebulisation and chest physiotherapy. Since discharge, the patient had only occasional shortness of breath, relieved by bronchodilators. She is considering expanded immunisation as well as enrolment in a clinical trial. Her hepatic AMLs will be monitored via ultrasound for growth. LAM treatment is generally aimed at its complications with lung transplantation reserved for severe disease; however, hormonal therapy and the mTOR inhibitor aim at targeting systemic disease.
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PMID:Tuberous sclerosis presenting with spontaneous pneumothorax secondary to lymphangioleiomyomatosis; previously mistaken for asthma. 2372 18

Insulinoma is a rare neuroendocrine pancreatic islet cell tumor of which the majority are benign and solitary. Its estimated incidence is 2 to 4 cases per 1 million person-years. We report the case of an 82-year-old female who presented with metastatic insulinoma to the liver and retroperitoneal lymph nodes. It was diagnosed based on positive Whipple's triad, elevated insulin, elevated C-peptide, and negative insulin auto-antibody. Her disease was initially managed with diazoxide 100 mg orally every 8 hours, octreotide LAR 30 mg intramuscularly every month, and sunitinib 12.5 mg orally three times a day. However, patient had recurrent symptoms and imaging consistent with worsened metastatic insulinoma; and thus, treatment was changed to everolimus 10 mg PO daily. Over the subsequent 10 months, the patient developed progressive shortness of breath and hypoxemia with and oxygen saturation (SpO2) of 89% on room air. Computerized tomography (CT) and lung biopsy were consistent with cryptogenic organizing pneumonia (COP) temporally associated with the initiation of everolimus. She was started on prednisone 1 mg/kg/day and within 48 hours, her symptoms and hypoxemia improved to SpO2 of 98-99% at room air and her repeat CT chest showed marked disease improvement. Given her good response with everolimus, it was continued in conjunction with the prednisone and to this day, patient has had a significant therapeutic response with normoglycemia and stable, well-controlled symptoms. This case is unique because to our knowledge, it is the first reported case of a patient with metastatic insulinoma complicated by the development of cryptogenic organizing pneumonia. It reaffirms the causal association between everolimus and cryptogenic organizing pneumonia that has been reported numerous times in literature. However, there has been no reported cases showing that the COP can be managed with prednisone concurrently with everolimus for the metastatic insulinoma without diminished clinical benefit. While pulmonary complications have been cited as reasons for discontinuation of everolimus therapy, our case report highlights the use of steroids as a viable therapeutic strategy that allows successful therapy with everolimus to be continued. In addition to presenting this case, we will also do a thorough review of the literature surrounding the available therapeutic options of metastatic insulinoma. This will include surgery, somatostatin analogs, antimicrobials, potassium channel activators, VEGF-A inhibitors, alkylating agents and mTOR inhibitors to provide a more in-depth picture of how we treat metastatic insulinoma.
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PMID:Refractory Metastatic Insulinoma Treated with Everolimus, Complicated by Cryptogenic Organizing Pneumonia. 3141 42

Diffuse idiopathic pulmonary neuroendocrine cell (DIPNECH syndrome) remains unfamiliar to most clinicians even though it was first described almost 30 years ago. Diagnosis is usually confirmed histopathologically after lung biopsy, but often, a diagnosis or suspected diagnosis can be made radiographically. In this paper, we present a case report of a 68-year-old female with shortness of breath and fleeting pulmonary nodules observed on chest CT scan. She was initially misdiagnosed with asthma based on an abnormal pulmonary function test which revealed an obstructive ventilatory defect. The classic radiographic findings of DIPNECH syndrome and the typical patient demographics that should arouse suspicion of a DIPNECH diagnosis were also illustrated. DIPNECH syndrome is a clinicopathological syndrome whereas focal NECH is a pathological diagnosis that is often made incidentally on histological examination and is encountered in a variety of settings, including in resected carcinoid tumors, in the context of reactive changes concomitant with infection, in metastatic cancer, radiation pneumonitis, intra-lobar sequestration, smokers, interstitial lung disease, and lung adenocarcinoma. There are no proven treatments for DIPNECH syndrome. In patients with obstructive ventilatory symptoms, bronchodilators with inhaled steroids are usually prescribed. Some severe cases may require parenteral steroids. Somatostatin analogs (SSA) have also been used in some cases with mixed results. Rapamycin has been used in several cases based on the purported activation of the mammalian target of rapamycin (mTOR) in DIPNECH. Some patients with large carcinoid tumors may benefit from resection.
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PMID:A 68-year-old woman with a diagnosis of asthma and multiple fleeting pulmonary nodules- a case report. 3329 53