Chyloperitoneum, chylothorax and lower extremity lymphedema in woman with sporadic lymphangioleiomyomatosis successfully treated with sirolimus: a case report.
ABSTRACT Lymphangioleiomyomatosis (LAM) is a rare disease characterized by diffuse thin-walled cysts throughout the lungs on computed tomography and diffuse proliferation of abnormal smooth muscle-like cells (LAM cells) on lung biopsy. LAM affects women almost exclusively, predominantly in their reproductive age. The most typical presenting symptoms include dyspnea, spontaneous pneumothorax, cough and chylothorax. Abdominal findings represent less common initial manifestations of the disease and may pose diagnostic difficulties. The treatment of LAM has not been fully established. Recent studies report effectiveness of sirolimus in LAM patients. We report the case of a 45-year-old woman with sporadic LAM, successfully treated with sirolimus, in whom the first manifestation of the disease was chyloperitoneum and after three and nine years, respectively, lymphedema of the left lower extremity and right sided chylothorax occurred.
Full-textDOI: · Available from: Mariusz Chabowski, Mar 02, 2014
Article: Update december 2012.Lymphatic Research and Biology 12/2012; 10(4):211-9. DOI:10.1089/lrb.2012.1042 · 1.66 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a key regulator of the PI3K/AKT/mTOR pathway, one of the downstream pathways activated by different intracellular mediators which control cell proliferation, differentiation, motility, survival, and metabolism. PTEN along with phosphoinositide 3-kinase makes up a regulatory hub which strictly controls the pool of the second lipid messenger, PtdIns(3,4,5)P3, an activator of the AKT/mTOR pathway. A genomic analysis of breast and other cancers revealed that this regulatory hub is vulnerable to cancer-driving mutations causing a constant activation of AKT signal. It was established that PTEN is a haploinsufficient tumor suppressor gene with one functional allele being insufficient to maintain wild-type function of PTEN which leads to cancer initiation in mice and humans. The observed PTEN dose-dependence of cancer susceptibility strongly indicates that PTEN is under strict control at both translational and post-translational levels. Haploinsufficiency at the PTEN gene is suggested to synergistically interact with post-translation inactivation of PTEN. More than 15 proteins regulate/inhibit PTEN activity through phosphorylation, ubiquitination, and acetylation via more than 15 PTEN regulatory sites. PTEN-modifier proteins form a PTEN regulatory network connecting the PI3K/AKT/mTOR pathway with multiple pathways relevant to cancer development. Heterozygous PTEN mutations were observed to cooperatively interact with genetic aberrations events in this regulatory network providing selective benefits in cancer progression. The PTEN regulatory network has been revealed to be a druggable target in cancer personalized therapy through restoration of PTEN activity in PTEN-deficient cancers.PTEN: Structure, Mechanisms-of-Action, Role in Cell Signaling and Regulation, Protein Science and Engineering edited by Ke Xu, 01/2013: chapter Role of Post-translational Regulation of PTEN Activity in Cancer Cell Addiction to Heterozygous PTEN Mutations: pages 173-210; Nova Publishers., ISBN: 978-1-62808-049-0
- [Show abstract] [Hide abstract]
ABSTRACT: Pneumothorax in pulmonary lymphangioleiomyomatosis (LAM) with tuberous sclerosis complex (TSC) is a difficult condition to manage. Video-assisted thoracoscopic surgery (VATS) may play a role in diagnosis and treatment of this situation. We present a case of right recurrent pneumothorax due to LAM with TSC in whom VATS was performed for pathological diagnosis and mechanical pleurodesis. The unique presentation of LAM in TSC was also discussed.Journal of Cardiothoracic Surgery 04/2013; 8(1):101. DOI:10.1186/1749-8090-8-101 · 3.05 Impact Factor