Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

The high prevalence of impulse control behaviors in patients with early-onset Parkinson's disease: A cross-sectional multicenter study.

INTRODUCTION: In Parkinson's disease patients, impulse control disorders (ICDs) have been associated with younger age and early disease onset, yet the prevalence of ICDs in early-onset Parkinson's disease (EOPD) patients has yet to be studied. Thus, we set out to compare the prevalence of impulse control behaviors (ICBs) in a cohort of EOPD patients with that in age and gender matched healthy controls (HCs), as well as to analyze the association of these symptoms with the use of dopaminergic drugs and other clinical or demographic factors. METHODS: A cross-sectional, multicenter study was carried out on patients recruited from outpatient Movement Disorder Clinics, assessing ICBs using the short form of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). In addition, depression and quality of life (QoL) were measured, along with other demographic and clinical variables. RESULTS: Of the 87 EOPD patients, 49 (58.3%) displayed an ICB, as did 28 of the 87 HCs (32.9%; p=0.001). Most of the EOPD patients that displayed an ICB (91.8%) were medicated with a dopamine agonist (DA) and accordingly, DA treatment was associated with a 7-fold increased risk of developing an ICB. Patients with ICBs had a higher depression score and a worse QoL. CONCLUSIONS: ICBs are much more prevalent in EOPD patients than in HCs and they are associated with DA intake, depression and a worse QoL.

Novel chemotherapy approaches in chemoradiation protocols.

Locally advanced cervical carcinoma had been treated with radiation therapy until 1999, when five different large clinical trials showed an overall survival benefit when chemotherapy was administered concomitantly with radiotherapy. The chemotherapy agents used in these trials were cisplatin, cisplatin combined with fluorouracil or hydroxyurea. Weekly cisplatin (40 mg/m(2)) achieved the best responses, even when compared with the combination with fluorouracil. These results led the United States National Cancer Institute (NCI) to recommend platinum-based chemotherapy for the treatment of locally advanced cervical carcinoma. Other cytotoxic agents have been tried in combination with radiotherapy for the management of the disease, including carboplatin, paclitaxel, gemcitabine and even topotecan. Gemcitabine has shown promising results and the combination of paclitaxel and carboplatin has proved safe and effective. However, to date, there has been no agent or combination of agents to have shown superiority over weekly cisplatin. Biologic agents such as bevacizumab, cetuximab, sorafenib and erlotinib are currently being tried in different trials in combination with radiotherapy and cisplatin. Celecoxib, a COX-2 inhibitor was evaluated in an RTOG study in combination with cisplatin and flourouracil with radiation therapy with no apparent effect on DFS and poor rates of locoregional control. Chemoradiation is the current standard therapy in locally advanced cervical carcinoma. The integration of novel agents will be established by the ongoing clinical trials.

Controversial origin of Pseudomyxoma peritonei

Pseudomyxoma peritonei describes the accumulation of mucinous material in the abdominal cavity. The main diagnostic problem appears when the primary site of origin could be appendix or ovary. In this paper describe clinicopathological features and biological markers that support appendiceal origin (AU)

[Comparative clinico-radiological study of lacunar infarcts of the cerebral hemispheres and brain stem in 110 cases]. / Estudio clinicorradiológico comparativo entre infartos lacunares hemisféricos y de tronco cerebral en 110 casos.

INTRODUCTION: Lacunar infarcts (LI) are small deep infarcts due to occlusion of perforating branches. OBJECTIVE: Our objective was to outline the clinical and epidemiological characteristics which differentiate hemispherical lacunar infarcts (HLI) from those of the brain stem (SLI). PATIENTS AND METHODS: We present 110 cases of LI (80 HLI, 30 SLI) analysing risk factors, clinical syndromes, findings on neurological examination (dysarthria, gravity, distribution and proportional paresia), form of clinical presentation, evolution whilst in hospital, site and results of carotid duplex. Diagnosis was made in 72 patients using magnetic resonance (MR) and in 38 patients using computerized axial tomography (CT). RESULTS: The commonest characteristics of SLI, as compared with HLI, with statistical significance (p < 0.05) was the appearance of supranuclear facial paresia (OR = 2.68), severe motor involvement (OR = 4.23), form of presentation with previous TIA (OR = 6.33), fluctuating evolution of the symptoms (OR = 5.78) and progression of the paresia (OR = 6.41). Also, in the pontine LI there was significant correlation between site and gravity: the lower the site of the lesion, the more serious was the paresia. Patients with multiple LI presented with no previous risk factors significantly more frequently than those with a single LI. CONCLUSION: The different clinical profiles may help to establish the subgroups of IL, according to where they occur.