This really interesting paper, referring the demonstration that activation of mTORC1 signaling is a critical step in adipocyte differentiation, identifying TSC2 as a primary target of Akt driving this process remember me an other excellent article (in Molecular Cell, 29, 541-551, from Gokhan Hotamisligil’s group suggesting that cellular stress might actually be helpful in certain contexts), that concludes: “…this study does point in a new direction for the development of a future therapeutic option in treating cancers that involve hyperactivation of mTOR”. First of all, the article from Gokhan Hotamisligil’s group underscores the central role played by TSC-deficiency in both Insulin-Resistance and apoptosis, as well as increased cell growth. I am delighted with such as paper. In fact, as I wrote also in Sponful of Medicine, I discovered and described a long time ago, from clinical viewpoint, numerous biophysical-semeiotic constitutions, among them the diabetic and oncological ones (Oncological Terrain). Notoriously, diabetes and cancer are associated often – certainly not due to casualty, i.e., by chance - in the same individuals. In a few words, the referred genetic, molecular-biological,oustanding results by Gokhan Hotamisligil’s group, agree with my old clinical data, indicating the existance of a bedside demarcation line (constitutions) in all most common and severe disorders, including diabetes and cancer. My 52-year-long clinical experience allows me to state that oncogenesis is possible exclusively in individuals Oncological Terrain-positive, involved by Inherited Oncological Real Risk .In my opinion, because the congenital functional mitochondrial cytopathology, which is the "conditio sine qua non" of the most common and dangerous human disorders, including malignancy, both solid and liquid, is overlooked, all current oncological primary preventions are fundamentally biased, and thus scarsely efficacious. I mean that authors do not consider the existence or assess the seriousness as well as the location of Congenital Acidosic Enzyme-Metabolic Histangiopathy, Oncological Terrain and thus Oncological Inherited Real Risk is based on, since such as mitochondrial cytopathology is overlooked (1-8). In fact, both environmental risk factors and every drug, as oestrogens, suggested as cancer risk factors, "could" influence some human biological functions and/or bring about different disorders, like cancers, exclusively in relation to both the presence and intensity of CAEMH-dependent Oncological Terrain and Oncological Inherited Real Risk in well-defined site of a (or more) biological system. I suggested this overlooked functional mitochondrial cytopathology, I have termed Congenital Acidosic Enzyme-Metabolic Histangiopathy, biophysical-semeiotic constitutions are based on, as the genetic factor of common human disorders, and particularly of malignancy (1-8). ("Oncological Terrain",in: www.semeioticabiofisica.i...), as far as the onset of a lot of disorders is concerned. At this point, I would analogously emphasise the well-known pathological powerful influence of smoking on tissue oxygen supply to all biological systems (3, 4). This effect varies notoriously in prevalence and intensity among individuals in relation to the above-mentioned congenital mitochondrial cytopathology, (2). This both "silent" and dangerous action is easy to evaluate at the bed-side with the aid of a stethoscope. Based on my long clinical experience, I suggest first investigating (i.e., before whatever research) the presence and intensity of CAEMH in the "tested" population, and soon thereafter assessing prevalence and intensity of the "Oncological Terrain" as well as Inherited Oncological Real Risk, which always develop on the basis of the above-mentioned congenital cytopathology, characterized by newborn-pathological, type I, subtype a), oncological, Endoarterial Blocking Devices, causing the typical microvascular remodelling (1-8). In fact, without this alteration of psycho-neuro-endocrine-immunological system, oncogenesis is not possible. The importance of the above-mentioned inherited real risk factor should not be overlooked from now on, particularly when we assess a "possible" risk factor for disorders biophysical-semeiotic constitution-dependent (9, 10).

1) Stagnaro S., Stagnaro-Neri M.Istangiopatia Congenita Acidosica Enzimo Metabolica. Gazz. Med. It.- Arch. Sci. Med. 144, 423, 1985.
2) Stagnaro S., Stagnaro-Neri M. Una patologia mitocondriale ignorata: la Istangiopatia Congenita Acidosica Enzimo-Metabolica. Gazz. Med. It. - Arch. Sci. Med. 149, 67 1990.
3)Stagnaro-Neri M., Stagnaro S. Deterministic Chaos, Preconditioning and Myocardial Oxygenation evaluated clinically with the aid of Biophysical Semeiotics in the Diagnosis of ischaemic Heart Disease even silent. Acta Med. Medit. 13, 109 1997.
4) Stagnaro-Neri M., Stagnaro S., Cancro della mammella: prevenzione primaria e diagnosi precoce con la percussione ascoltata. Gazz. Med. It. � Arch. Sc. Med. 152, 447 1993
5) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004. http://www.travelfactory....
6) Stagnaro S., Stagnaro-Neri M., Oncological Terrain, conditio sine qua non of Oncogenesis, 2004: http://www.gutjnl.com/cgi...
7) Stagnaro Sergio. "Genes, Oncological Terrain, and Breast Cancer" World Journal of Surgical Oncology., 2005, http://www.wjso.com/conte...
8) Stagnaro S. Reale Rischio Semeiotico-Biofisico. Ruolo diagnostico e patogenetico dei Dispositivi Endoarteriolari di Blocco neoformati patologici tipo I, sottotipo a) oncologici e b). Ed Travel Factory, Roma, www.travelfactory.it, in press
9) Stagnaro S. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/...
10) Sergio Stagnaro. Mitochondrial Genome of the Mastodon highlights Human Constitutions. PLOS Biology, (01 August 2007) http://biology.plosjourna...