The second hit event in LAM cells is often loss of the chromosomal region containing the wild-type copy of the TSC2 gene; this is referred to as loss of heterozygosity or LOH. LOH can be detected in microdissected LAM cells, in angiomyolipomas and lymph nodes from women with LAM, and in circulating LAM cells (cells in blood and urine).Angiomyolipomas and pulmonary LAM cells from women with the sporadic form of LAM carry identical mutations in TSC2. This, together with the fact that recurrent LAM after lung transplantation carries the same TSC2 mutations as the original LAM, has led to the "benign metastasis" hypothesis that LAM cells can migrate or metastasize from one site to another. Pathophysiology
A variable percentage of cells within the LAM lesion contain mutational inactivation of the tuberous sclerosis complex (TSC1 or TSC2) tumor suppressor genes. TSC1 mutations cause a less severe clinical phenotype than TSC2 mutations. The discovery of TSC1/2 gene function as negative regulator of the mammalian target of rapamycin complex 1 (mTORC1) led to successful use of rapamycin analog sirolimus in clinical trials and FDA approval of sirolimus for treatment of LAM. TSC1 and TSC2 form a tumor suppressor complex that regulates mammalian target of rapamycin (mTOR) signaling complex by directly controlling the activity of the small GTPase Rheb via the GTPase activating protein (GAP) domain of TSC2. Rheb binds to Raptor and controls the activity of mTOR complex 1 (mTORC1) that directly phosphorylates p70 S6 kinase (S6K1) and 4E-BP1.
Contact with a sprayed plant or "weed" can have an effect upon local wildlife, most notably insects. A cause for concern is how pests, the reason for pesticide use, are building up a resistance. Phytophagous insects are able to build up this resistance because they are easily capable of evolutionary diversification and adaptation. The problem this presents is that in order to obtain the same desired effect of the pesticides they have to be made increasingly stronger as time goes on. Repercussions of the use of stronger pesticides on vegetation has a negative result on the surrounding environment, but also would contribute to consumers long-term low-level exposure. See also
Health effects of pesticides
SENSOR-Pesticides program
WHO Pesticide Evaluation Scheme

Notes
References
Cited texts


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