Wnt7a is a novel inducer of ß-catenin-independent tumor-suppressive cellular senescence in lung cancer.

Cellular senescence is an initial barrier for carcinogenesis. However, the signaling mechanisms that trigger cellular senescence are incompletely understood, particularly in vivo. Here we identify Wnt7a as a novel upstream inducer of cellular senescence. In two different mouse strains (C57Bl/6J and FVB/NJ), we show that the loss of Wnt7a is a major contributing factor for increased lung tumorigenesis owing to reduced cellular senescence, and not reduced apoptosis, or autophagy. Wnt7a-null mice under de novo conditions and in both the strains display E-cadherin-to-N-cadherin switch, reduced expression of cellular senescence markers and reduced expression of senescence-associated secretory phenotype, indicating a genetic predisposition of these mice to increased carcinogen-induced lung tumorigenesis. Interestingly, Wnt7a induced an alternate senescence pathway, which was independent of ß-catenin, and distinct from that of classical oncogene-induced senescence mediated by the well-known p16(INK4a) and p19(ARF) pathways. Mechanistically, Wnt7a induced cellular senescence via inactivation of S-phase kinase-associated protein 2, an important alternate regulator of cellular senescence. Additionally, we identified Iloprost, a prostacyclin analog, which initiates downstream signaling cascades similar to that of Wnt7a, as a novel inducer of cellular senescence, presenting potential future clinical translational strategies. Thus pro-senescence therapies using either Wnt7a or its mimic, Iloprost, might represent a new class of therapeutic treatments for lung cancer.

[Panic disorder and transcranial magnetic stimulation]. / Trastorno de angustia y estimulación magnética transcraneal.

Transcranial magnetic stimulation (TMS) has been tried in some Anxiety Disorders (Obsessive-compulsive disorder and Posttraumatic Stress Disorder) with different results. We present a pilot study including three Panic Disorder patients. The subjects who were enrolled had a history of the disease for at least 1 year and they had unsuccessfully followed psychotherapy and pharmacological treatment. The patients received 10 sessions during two weeks; each session lasted 30 trains of 60 seconds at a frequency of 1 Hz, on the right dorsolateral prefrontal cortex, at 110% of the motor threshold. All three patients experienced a modest and partial symptom improvement that did not seemed to be clinically relevant. Two patients accepted to participate in a TMS second phase, where the previous stimulation parameters were alternated with an application of 30 trains of 20 Hz during 2 seconds on the left prefrontal cortex. This alternate application of high and low frequency TMS in each session was also well tolerated, but failed to produce additional improvement. In addition to presenting these three cases, we emphasize some features concerning the neurobiological basis of the anxiety disorders and we connect them to the previously described TMS neurophysiological actions in order to justify further investigation.

Moving to the routine management of pre symptomatic lung cancer.

Lung cancer is the world's leading cause of cancer death. Since progress in the treatment of this cancer has been exceedingly slow, the upswing in tobacco consumption in many sectors becomes even more tragic. One area for cautious optimism is the recent pilot reports of improved early lung cancer detection using new spiral CT techniques from institutions in Japan and New York. The prospect of improved early detection in a major cancer raises a number of public health concerns and highlights the importance of critical validation of this proposed new tool. From experience with early detection-based management of other cancers, it is evident that the entire process of detection, case validation, intervention, monitoring and public education needs to be carefully developed. The International Association for the Study of Lung Cancer has worked with the National Cancer Institute over the last decade to nurture interest and expertise in conducting population-based management of early lung cancer. A distillation of this process up to the current time is reviewed in this manuscript.

[Guirod's hebephrenic syndrome: a case report]. / El Síndrome Hebefrénico de Guirod: a propósito de un caso.

Schizophrenia, a psychiatric disease that is highly prevalent among the general population, has polymorphic clinical manifestations at onset and during its evolution. The most frequent manifestations are an abrupt onset with positive symptoms, perception and thought disorders, which were included by Kurt Schneider in the first range symptoms. However, on other occasions the onset is insidious and the so-called negative symptoms are present, resulting in clinical manifestations that are similar to the state of absence and a less favorable patient prognosis. Since the last century when Kraepelin defined early dementia, various authors have tried to explain the nature of this disease, resulting in Bleauler's definition of the fundamental symptoms. A clinical case of hebephrenic schizophrenia is presented in which disorders in thought, affect and volition predominated. We discuss the psychopathological views of less well-known, but not for that reason less important, authors, such as Guirod and Dice, and the similarities and differences between their views and current classifications.