SCIENTIFIC RESEARCH:
New LAM Research
November 2009
A contract has been signed and work begins this month at the Malaghan Institute for Medical Research in Wellington.
The Agreement to fund a one year pilot programme of new LAM Research is between the Malaghan Institute's Cancer Cell and Molecular Biology Group and The New Zealand LAM Trust in collaboration with LAM Australasia Research Alliance (LARA).
The Wellington based work which is part of a proposed three year study will be undertaken by Professor Mike Berridge and his team at the Institute, in collaboration with Dr Lyn Moir from Professor Judy Black's lab at the University of Sydney.
The Project will investigate the cancer-like properties of LAM cells; in particular, whether LAM cells can grow in culture, under conditions that support the growth of self-renewing cancer cells. The team will investigate whether LAM cells grown in these conditions, express self renewal genes typical of cancer stem cells.This work is designed to be part of a larger study that will explore the feasibility of treating LAM, using the immunological therapies currently being developed for treating cancer.
Both the Australian and New Zealand LAM patient organisations which have raised the money for this project wish to thank supporters for their donations that have made this work possible and we wish the research teams well in the first year of this exciting programme.
Feasibility of Immunotherapy for Lymphangioleiomyomatosis
published in The American Journal of Pathology
November 2009
From the Department of Pathology and the Cancer Research
Center, University of Hawaii, Honolulu, Hawaii
LAM strikes women during their reproductive years and
leaves patients with a much reduced life expectancy at
diagnosis. Patients with LAM present with recurrent
pneumothoraces, hemoptysis, pleural effusions, and dyspnea
on exertion. There is no truly effective treatment
available beyond lung transplantation. LAM is definitively
diagnosed by detecting expression of the glycoprotein
recognized by the antibody HMB45. Differential diagnosis
is otherwise difficult, and patients with sporadic LAM
typically remain undiagnosed for several years. > more
Melanoma–Associated Antigen Expression in
Lymphangioleiomyomatosis Renders Tumor Cells Susceptible to Cytotoxic T Cells
published in The American Journal of Pathology
November 2009
From the Departments of Pathology, Microbiology and
Immunology/Oncology Institute,* and Department of Surgery,†
Loyola University, Chicago, Illinois; Illinois Math and Science
Academy,‡ Aurora, Illinois; Department of Medicine,§ Loyola
University, Chicago, Illinois; Department of Surgery,¶ University
of Chicago, Chicago, Illinois; Department of Dermatology,
University of Cincinnati, Cincinnati, Ohio; and Department of
Surgery,** Medical University of South Carolina, Charleston,
South Carolina
Following the identification of underlying mutations
responsible for the symptoms incurred in LAM and
intracellular signaling pathways affected by TSC1/TSC2
through the mammalian target of rapamycin complex,
proposed disease treatments have been aimed at the
hyperproliferative responses observed in mutant cells.
The mammalian target of rapamycin inhibitor rapamycin
has been tested in phase 1 trials with mixed results. > more
Molecular Pathogenisis of LAM published in American Journal of Respiratory, Cell and Molecular Biology
December 2007
Lymphangioleiomyomatosis (LAM) is a rare progressive cystic lung
disease affecting young women. The pivotal observation that LAM
occurs both spontaneously and as part of the tuberous sclerosis
complex (TSC) led to the hypothesis that these disorders share
common genetic and pathogenetic mechanisms. In this review we
describe the evolution of our understanding of the molecular and
cellular basis of LAM and TSC, beginning with the discovery of the
TSC1 and TSC2 genes and the demonstration of their involvement
in sporadic (non-TSC) LAM. This was followed by rapid delineation
of the signaling pathways in Drosophila melanogaster with confirmation
in mice and humans. This knowledge served as the foundation
for novel therapeutic approaches that are currently being used in
human clinical trials. > more
Collaborative Programme of Scientific
Investigation into LAM
As a result of three years of work by The New Zealand LAM Trust, the team of New Zealand and Australian researchers (pictured right) are working against the clock as part of an international collaborative effort to uncover answers to the causes of this rare and cruel disease.
Dr Lyn Moir began her work at The University of Pennsylvania in the lab of Dr Vera Krymskaya in June 2007. Dr Moir will return to The University of Sydney in 2008, and it is hoped that funds will be raised to enable her to continue her cell signalling work there.
A presentation abstract on the work completed in Philadelphia will be made at the American Thoracic Society's annual meeting in Toronto in 2008 and at the Australasian Thoracic meeting in Melbourne in May 2008.
Lymphangioleiomyomatosis
by Francis McCormack, MD
Lymphangioleiomyomatosis (LAM) is a rare, progressive, cystic lung disease that occurs almost exclusively in females, usually between menarche and menopause. The hallmarks of LAM are diffuse infiltration of the pulmonary parenchyma with atypical smooth muscle cells, airflow obstruction, pneumothorax and chylothorax, and progressive respiratory failure... > more
Australian Scientific Investigation
In June 2004 the prestigious UK Journal of Pathology published a Paper from Professor Mervyn J Merrilees, principal investigator,University of Auckland in conjunction with Professor Judith L. Black, University of Sydney. The paper is titled "Matrix Proteoglycans and remodelling of interstial lung tissue in Lymphangioleiomyomatosis (LAM)".
This Paper can be seen on line in Wylie InterScience (www.interscience.wiley.com) and is published in J Pathol 2004; no 203: 653-660.
Currently, NZ LAM Trust funded LAM science investigation continues at the University of Auckland.
Professor Merrilees and his team's recent studies (UK Journal of Path) have shown that LAM is characterised not only by the growth of defective smooth muscle cells, but also by significant amounts of interstitial tissue that contain normal fibroblasts and large amounts of space occupying matrix proteoglycans.
Of particular interest is the finding that areas rich in proteoglycans are depleted in elastic fibres which are essential to the proper functioning of the lung during breathing.
Prof Merrilees and the team have been working with the drug rapamycin which has been found to be a very effective inhibiter of cell migration.
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