Lhx6 regulates the migration of cortical interneurons from the ventral telencephalon but does not specify their GABA phenotype

The LIM homeodomain family of transcription factors is involved in many processes in the developing CNS, ranging from cell fate specification to connectivity. A member of this family of transcription factors, lhx6, is expressed in the medial ganglionic eminence(MGE) of the ventral telencephalon, where the vast majority of cortical interneurons are generated. Its expression in the GABA-containing MGE cells that migrate to the cortex suggests that this gene uniquely or in combination with other transcription factors may play a role in the neurochemical identity and migration of these neurons. We performed loss of function studies for lhx6 in mouse embryonic day 13.5 brain slices and dissociated MGE neuronal cultures using Lhx6-targeted small interfering RNA produced by a U6 promoter-driven vector. We found that silencing lhx6 impeded the tangential migration of interneurons into the cortex, although it did not obstruct their dispersion within the ganglionic eminence. Blocking lhx6 expression in dissociated MGE cultured neurons did not interfere with the production of GABA or its synthesizing enzyme. These results indicate that lhx6, unlike the closely related member lhx7, does not regulate neurotransmitter choice in interneurons but plays an important role in their migration from the ventral telencephalon to the neocortex

Tensegrity structures for the Hellenic Maritime Museum

p. 2233-2242Tensegrity structures composed of masts and cables bear similarities and carry metaphoric associations to nautical equipment and structures. Such metaphors have suggested the use of the tensegrity concept in the design of the lightweight structures for the Hellenic Maritime Museum. Two different types of lightweight structures have been studied. At an early design stage scaled models of existing tensegrity configurations were considered, and subsequently several new tensegrity configurations have been developed and studied. Morphological variations of tensegrity structures that occur from the assembly of new units have also been studied. A canopy structure composed of prismatic tensegrity units of irregular geometry with an attached membrane and a large space enclosing tensegrity structure have been developed. The paper presents and discusses the configuration of the two tensegrity structures for the maritime museum and the challenges encountered in their geometric & structural design.Liapi, KA. (2010). Tensegrity structures for the Hellenic Maritime Museum. Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/727

Paraneoplastic Cerebellar Ataxia Can Affect Prognosis in High-Grade Serous Ovarian Cancer: A Case Report.

The reported case is a 61-year-old woman, admitted for gradual onset of gait disturbances and dysphonia. The serum immunological panel revealed anti-Yo autoantibodies, suggestive of a paraneoplastic syndrome (PNS). A PET-CT revealed a suspicious left ovarian mass with retroperitoneal nodal involvement, and the histological assessment of surgical samples confirmed a FIGO IIIC high-grade serous ovarian cancer (HGSOC). Deemed inoperable at first, the patient was treated by carboplatin and paclitaxel chemotherapy, after which she refused surgical debulking. At the end of her systemic treatment, the patient only experienced a transient improvement of the cerebellar ataxia. Despite the suboptimal oncological treatment, the patient still presents stable disease and is free of progression 7 years from her diagnosis. This case study illustrates the favorable effect of PNS occurrence on oncological outcome in a patient with advanced HGSOC. The absence of recurrence despite the presence of residual disease after the systemic treatment is unusual and could be related to the PNS

Longitudinal Imaging And Clinical Assessment Of Patients With Unresectable Hepatocellular Carcinoma Treated With Transcatheter Arterial Chemoembolization

Statement of problem: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death and often arises in the context of hepatic cirrhosis. Transcatheter arterial chemoembolization (TACE) is a non-surgical treatment for patients with unresectable HCC involving local and targeted intra-arterial delivery of chemotherapy. Currently, it is unclear whether overall survival in patients with HCC treated with TACE can be predicted by longitudinally measured clinical and imaging biomarkers. The aim of this study was to determine whether longitudinally collected metrics might contribute to the prediction of overall patient survival. Materials and Methods: This IRB-approved cohort study included 211 consecutive patients with unresectable HCC treated with TACE between 1/1/2001 and 11/28/2008. A complete case analysis was performed on baseline and longitudinally collected clinical and imaging data of 119 patients. Baseline (time-independent) and longitudinal (time-dependent) data included age, gender, ethnicity, type of cirrhosis and Eastern European Cooperative Group (ECOG) performance status. Time-dependent data included Child-Turcotte-Pugh (CTP) score, tumor burden, longest tumor size, portal vein thrombosis, tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 and modified RECIST. Overall survival estimates were calculated by the Kaplan-Meier method. Cox regression models were used to predict the effect of time-independent and time-dependent variables on overall survival. Results: Mean overall survival was 18.85 months (median 14, range: 1-148). The analysis of time-independent Cox models revealed that portal vein thrombosis (HR= 2.47, 95% CI= 1.32-4.64, p=0.01) and uni-dimensional tumor size greater than 5 cm (5-7.99 cm, HR= 3.16, 95% CI=1.27-7.90, p=0.01; 8-11.99 cm, HR=3.37, 95% CI=1.37-8.30, p=0.01; >12 cm, HR=3.56, 95% CI= 2.46-22.53, p<0.0001) were independent baseline predictors of decreased overall survival, after adjusting for ethnicity and etiology of cirrhosis. The analysis of time-dependent Cox models revealed that an ECOG status of 1 or 2 (adjusted HR=1.83, 95% CI=1.11-3.03, p=0.02,) and a CTP score of B (adjusted HR=1.50, 95% CI=1.07-2.12, p=0.02), were independent time-varying predictors of decreased overall survival. Conclusion: The results of our statistical analyses using time-dependent variables highlights the prognostic value of longitudinally collected markers and should alert clinicians to the value of their collection and assessment

VEGFR Inhibitors for Uterine Metastatic Perivascular Epithelioid Tumors (PEComa) Resistant to mTOR Inhibitors. A Case Report and Review of Literature.

Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms. PI3K/AKT/mTOR pathway upregulation is critical for their pathogenesis and is often associated with TSC1/TSC2 inactivation. Although first line mTOR inhibitors are an effective treatment, metastatic PEComas eventually progress. A 53-year-old woman presented a 4-month history of post-menopausal vaginal bleeding. Clinical and radiological examination detected a uterine mass and a single S1 bone lesion. The patient underwent a radical hysterectomy and bone biopsy. The anatomopathological evaluation concluded to an oligo-metastatic uterine PEComa. The tumor harbored a heterozygous deletion of 9q34 that contains the TSC1 gene. Concerning the primary lesion, the resection was complete and the single bone metastasis was treated with radiotherapy. Three months later, the patient presented bone, lung and subcutaneous metastatic progression. An everolimus and denosumab treatment was initiated. After 2 years of treatment, a clinically significant bone, lung and subcutaneous progression was detected. Following a literature review of the possible therapeutic options, we initiated a second line treatment by pazopanib. This treatment resulted in regression of the subcutaneous lesions and stability of lung and bone metastases. In this challenging, rare setting, our report suggests single agent, anti-angiogenic, tyrosine kinase inhibitor to be effective as second line treatment of metastatic uterine PEComa progressing on mTOR inhibitors

Lymph Node Involvement in Recurrent Serous Borderline Ovarian Tumors: Current Evidence, Controversies, and a Review of the Literature.

Borderline ovarian tumors (BOTs) account for 10-20% of epithelial ovarian neoplasms. They are characterized by their lack of destructive stromal invasion. In comparison to invasive ovarian cancers, BOTs occur in younger patients and have better outcome. Serous borderline ovarian tumor (SBOT) represents the most common subtype of BOT. Complete surgical staging is the current standard management but fertility-sparing surgery is an option for SBOT patients who are at reproductive age. While most cases of SBOTs have an indolent course with favorable prognosis, late recurrence and malignant transformation can occur, usually in the form of low-grade serous carcinoma (LGSC). Thus, assessment of the recurrence risk is essential for the management of those patients. SBOTs can be associated with lymph node involvement (LNI) in up to 30% of patients who undergo lymph node dissection at diagnosis, and whether LNI affects prognosis is controversial. The present review suggests that recurrent SBOTs with LNI have poorer oncological outcomes and highlights the biases due to the scarcity of reports in the literature. Preventing SBOTs from recurring and becoming invasive overtime and a more profound understanding of the underlying mechanisms at play are necessary