Long noncoding RNAs and neuroblastoma

Neuroblastoma is a disease that affects infants and despite intense multimodal therapy, high-risk patients have low survival rates (<50%). In recent years long noncoding RNAs (lncRNAs) have become the cutting edge of cancer research with inroads made in understanding their roles in multiple cancer types, including prostate and breast cancers. The roles of lncRNAs in neuroblastoma have just begun to be elucidated. This review summarises where we are with regards to lncRNAs in neuroblastoma. The known mechanistic roles of lncRNAs during neuroblastoma pathogenesis are discussed, as well as the relationship between lncRNA expression and the differentiation capacity of neuroblastoma cells. We speculate about the use of some of these lncRNAs, such as those mapping to the 6p22 hotspot, as biomarkers for neuroblastoma prognosis and treatment. This novel way of thinking about both neuroblastoma and lncRNAs brings a new perspective to the prognosis and treatment of high-risk patients.     

Gender and Nationality Trends in Manuscripts Published in Prominent Gastroenterology Journals Between 1997 and 2017

Digestive Diseases and Sciences - Gender disparities remain in the field of gastroenterology (GI) despite the decreasing gender gap in the medical field overall. We sought to examine primary and...     

Graphynes: indispensable nanoporous architectures in carbon flatland

Theoretical design and experimental realization of novel nanoporous architectures in carbon membranes has been a success story in recent times. Research on graphynes, an interesting class of materials in carbon flatland, has contributed immensely to this success story. Graphyne frameworks possessing sp and sp² hybridized carbon atoms offer a variety of uniformly distributed nanoporous architectures for applications ranging from water desalination, gas separation, and energy storage to catalysis. Theory has played a pivotal role in research on graphynes, starting from the prediction of various structural forms to the emergence of their remarkable applications. Herein, we attempt to provide an up-to-date account of research on graphynes, highlighting contributions from numerous theoretical investigations that have led to the current status of graphynes as indispensable materials in carbon flatland. Despite unsolved challenges in large-scale synthesis, the future appears bright for graphynes in present theoretical and experimental research scenarios.

The uniformly distributed nanoporous architectures in graphynes have significantly expanded the applicability of the materials of carbon flatland in areas such as water desalination, gas separation, energy storage, catalysis and optoelectronics.     

Choroidal metastases: Origin,features, and therapy

The choroid is the most common ocular site for metastatic disease, owing to abundant vascular supply. The primary cancers that most commonly lead to choroidal metastases include breast cancer (40-47%) and lung cancer (21-29%). Bilateral, multifocal metastases are most often secondary to breast cancer, whereas unilateral, unifocal metastasis are more commonly found with lung cancer. The treatment of choroidal metastasis depends on the systemic status of the patient and number, location, and laterality of the choroidal tumors. Treatment options include observation in patients with poor systemic status or those with resolved or asymptomatic disease; systemic chemotherapy, immunotherapy, hormone therapy, or whole eye radiotherapy if the metastases are active, multifocal and bilateral; plaque radiotherapy, transpupillary radiotherapy, or photodynamic therapy for active, solitary metastasis; and enucleation for those with blind painful eye. A database search was performed on PubMed, using the terms “choroidal metastasis,” or “choroidal metastases,” in combination with terms such as “treatment,” “features,” or “diagnosis.” Relevant articles were extracted and reviewed.     

Mammalian Target of Rapamycin (mTOR) Regulates Cellular Proliferation and Tumor Growth in Urothelial Carcinoma

Mammalian target of rapamycin (mTOR) signaling has been associated with aggressive tumor growth in many cancer models, although its role in urothelial carcinoma (UCC) has not been extensively explored. Expression of phosphorylated mTOR (P-mTOR) and a downstream target, ribosomal S6 protein (P-S6), was identified in 74% (90/121) and 55% (66/121) of muscle-invasive UCCs, respectively. P-mTOR intensity and %positive cells were associated with reduced disease-specific survival (P = 0.04, P = 0.08, respectively). Moreover, P-mTOR intensity corresponded to increased pathological stage (P < 0.01), and mTOR activity was associated with cell migration in vitro. In addition, mTOR inhibition via rapamycin administration reduced cell proliferation in UCC cell lines RT4, T24, J82, and UMUC3 in a dose-dependent manner to 6% of control levels and was significant at 1 nmol/L in J82, T24, and RT4 cells (P < 0.01, P < 0.01, P = 0.03, respectively) and at 10 nmol/L in UMUC3 cells (P = 0.03). Reduced proliferation corresponded with reduced P-S6 levels by Western blot, and effects were ablated by pretreatment of cells with mTOR-specific siRNA. No effects of rapamycin on apoptosis were identified by TUNEL labeling or PARP cleavage. Administration of rapamycin to T24-xenografted mice resulted in a 55% reduction in tumor volume (P = 0.03) and a 40% reduction in proliferation (P < 0.01) compared with vehicle-injected mice. These findings indicate that mTOR pathway activation frequently occurs in UCC and that mTOR inhibition may be a potential means to reduce UCC growth.Bladder cancer occurs in multiple forms, the most common of which is urothelial carcinoma (UCC), which represents >90% of all bladder cancers.¹ Approximately 30 to 50% of patients with invasive bladder cancer into the muscular wall of the bladder will develop metastatic disease and die within 2 years of diagnosis.² In addition, virtually all patients diagnosed with distant UCC metastases will succumb to disease.³ Currently, the standard treatment modality for muscle-invasive bladder cancer is radical cystectomy; systemic chemotherapy is generally reserved for patients with metastatic disease, although these treatment regimens provide only a limited long-term benefit with only rare reports of complete remission.^4,5 In light of these clinical outcomes, identification of new therapeutic targets is needed to define potential additional treatment avenues for these patients.Activation of the mammalian target of rapamycin (mTOR) signaling pathway occurs in many cancers and has recently been shown to correlate with more aggressive disease behavior,^6,7,8,9 although it has not been examined in great detail in UCC. Activation of mTOR occurs via a multistep process that includes upstream phosphoinositide-3 kinase (PI3K) and AKT activation, leading to phosphorylation and inactivation of the tuberous sclerosis complex 1 and 2 (TSC1/TSC2) heterodimer.^10,11 Inactivation of this heterodimer results in release of Rheb inhibition and subsequent mTOR activation by means of Rheb GTPase activity. Once activated, mTOR can induce increased mRNA translation or regulate the actin cytoskeleton via differential association Rictor and Raptor proteins.^10,11 Ultimately, mTOR activity regulates the effects of a number of downstream molecules important in cellular growth, including p70 S6 kinase-1 (S6K) and elongation-initiation factor 4E binding protein-1 (4E-BP1). Selective inhibition of the mTOR pathway can be achieved using rapamycin or rapamycin analogs temsirolimus (CCI-779, Wyeth Pharmaceuticals) and everolimus (RAD001, Novartis), which are currently in use in numerous clinical trials for solid tumors, with promising results in patients with advanced renal cell carcinoma.^12,13To further investigate the potential role of mTOR signaling and inhibition in UCC of the bladder, we used human cancer specimens, xenograft models, and in vitro analysis to determine the effects of mTOR on cellular proliferation, apoptosis, tumor growth, and clinical outcomes in this cancer population.