High-efficiency liposomal encapsulation of a tyrosine kinase inhibitor leads to improved in vivo toxicity and tumor response profile.

Staurosporine (STS) is a potent pan-kinase inhibitor with marked activity against several chemotherapy-resistant tumor types in vitro. The translational progress of this compound has been hindered by poor pharmacokinetics and toxicity. We sought to determine whether liposomal encapsulation of STS would enhance antitumor efficacy and reduce toxicity, thereby supporting the feasibility of further preclinical development.

PTEN status mediates 2ME2 anti-tumor efficacy in preclinical glioblastoma models: role of HIF1α suppression.

Glioblastoma (GBM) is the most common brain cancer and is highly lethal in both adults and children. 2-methoxyestradiol (2ME2) is a microtubule inhibitor that potently inhibits HIF1α, GBM angiogenesis and tumor growth in preclinical models. In patients, 2ME2 exhibits low toxicity and promising but inconsistent efficacy.

Oviposition behaviour of Phlebotomus argentipes--a laboratory-based study.

The breeding habitat of sandflies is a little studied and poorly understood phenomenon. More importantly, oviposition behaviour is a largely neglected aspect of sandfly biology and this knowledge gap further undermines our understanding of the biology of sandflies. Pheromones released by the eggs play an important role in identifying good sites for oviposition by female insects.

Clinical trials of viral therapy for malignant gliomas.

Despite recent scientific advances in the understanding of the biology of malignant gliomas, there has been little change in the overall survival for this devastating disease. New and innovative treatments are under constant investigation. Starting in the 1990s, there was an interest in using viral therapeutics for the treatment of malignant gliomas.

Restriction-Spectrum Imaging of Bevacizumab-Related Necrosis in a Patient with GBM.

Importance: With the increasing use of antiangiogenic agents in the treatment of high-grade gliomas, we are becoming increasingly aware of distinctive imaging findings seen in a subset of patients treated with these agents. Of particular interest is the development of regions of marked and persistent restricted diffusion. We describe a case with histopathologic validation, confirming that this region of restricted diffusion represents necrosis and not viable tumor.

Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging.

Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in malignant glioma. Conventional methods for assessment of BBB penetrance require synthesis of isotopically labeled drug derivatives. Here, we report a new methodology using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue without molecular labeling.

An EGFR wild type-EGFRvIII-HB-EGF feed-forward loop regulates the activation of EGFRvIII.

EGFRvIII is a key oncogene in glioblastoma (GBM). EGFRvIII results from an in-frame deletion in the extracellular domain of EGFR, does not bind ligand and is thought to be constitutively active. Although EGFRvIII dimerization is known to activate EGFRvIII, the factors that drive EGFRvIII dimerization and activation are not well understood.

User friendliness, efficiency & spray quality of stirrup pumps versus hand compression pumps for indoor residual spraying.

Background & Objectives: Indoor residual spraying (IRS) is a proven tool to reduce visceral leishmaniasis vectors in endemic villages. In India IRS is being done with stirrup pumps, whereas Nepal, Bangladesh, and other countries use compression pumps. The present study was conducted with the objectives to compare the efficiency, cost and user friendliness of stirrup and compression pumps.

Determinants of respiratory diseases in East Sikkim.

Background: Due to the difficult geographic terrain with lack of roads and transport, the Sikkim State in India finds difficulties in contending the respiratory diseases especially during the rainy seasons.

Findings: A case-control study was conducted for two months at the Central Referral Hospital of East Sikkim involving 110 individuals in the age group of 10 years and above. Due to feasibility constraints, 55 cases and 55 controls were selected by applying the non-probability sampling method with age and sex matching.

Retrospective study of pemetrexed as salvage therapy for central nervous system lymphoma.

There is currently no standard therapy for recurrent or chemotherapy-refractory central nervous system lymphoma (CNSL). Pemetrexed has been reported to have activity in patients with primary CNSL (PCNSL). The use of pemetrexed in secondary CNS lymphoma (SCNSL) has not previously been reported.

Swedish review strengthens grounds for concluding that radiation from cellular and cordless phones is a probable human carcinogen.

With 5.9 billion reported users, mobile phones constitute a new, ubiquitous and rapidly growing exposure worldwide. Mobile phones are two-way microwave radios that also emit low levels of electromagnetic radiation.

Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI.

Scavenger receptors (SRs) are molecular pattern recognition receptors that have been shown to mediate opsonin-independent uptake of therapeutic and imaging nanoparticles, underlying the importance of SRs in nanomedicine. Unlike pathogens, engineered nanomaterials offer great flexibility in control of surface properties, allowing addressing specific questions regarding the molecular mechanisms of nanoparticle recognition. Recently, we showed that SR-type AI/II mediates opsonin-independent internalization of dextran superparamagnetic iron oxide (SPIO) nanoparticles via positively charged extracellular collagen-like domain.

Leptomeningeal metastases in breast cancer.

Central nervous system (CNS) metastasis from breast cancer may be characterized as either parenchymal brain metastasis (BM) or leptomeningeal (LM) metastasis. BM are much more common (about 80% of all CNS metastases), and have been more extensively studied than LM. CNS metastasis in breast cancer has been associated with reduced overall survival, with the shortest survival generally observed in cases of LM.

Appraisal of Phlebotomus argentipes habitat suitability using a remotely sensed index in the kala-azar endemic focus of Bihar, India.

Visceral leishmaniasis, or kala-azar, is recognised as a serious emerging public health problem in India. In this study, environmental parameters, such as land surface temperature (LST) and renormalised difference vegetation indices (RDVI), were used to delineate the association between environmental variables and Phlebotomus argentipes abundance in a representative endemic region of Bihar, India. The adult P.

Longitudinal restriction spectrum imaging is resistant to pseudoresponse in patients with high-grade gliomas treated with bevacizumab.

Background And Purpose: Antiangiogenic therapies, such as bevacizumab, decrease contrast enhancement and FLAIR hyperintensity in patients with high-grade gliomas in a manner that may not correlate with actual tumor response. This study evaluated the ability of an advanced DWI technique, restriction spectrum imaging, to improve conspicuity within regions of restricted diffusion compared with ADC in patients treated with bevacizumab and to demonstrate that unlike ADC, restriction spectrum imaging is less affected by bevacizumab-induced reductions in FLAIR hyperintensity.

Materials And Methods: Restriction spectrum imaging cellularity maps and DWI were available for 12 patients with recurrent high-grade gliomas at baseline and following initiation of bevacizumab.

Glucose corrected standardized uptake value (SUVgluc) in the evaluation of brain lesions with 18F-FDG PET.

Purpose: To retrospectively assess the utility of (18)F fluorodeoxyglucose (FDG) positron emission tomography (PET) images of standardized uptake values corrected for blood glucose (SUV(gluc)), and to compare this to various quantitative methods to identify the presence or absence of high grade malignancy.

Methods: A retrospective review in 42 patients, found 81 central nervous system (CNS) lesions. Fifty one were malignant and 30 were benign or post treatment changes based on pathology (n = 32) and on clinical outcome (n = 49).

Protein interaction discovery using parallel analysis of translated ORFs (PLATO).

Identifying physical interactions between proteins and other molecules is a critical aspect of biological analysis. Here we describe PLATO, an in vitro method for mapping such interactions by affinity enrichment of a library of full-length open reading frames displayed on ribosomes, followed by massively parallel analysis using DNA sequencing. We demonstrate the broad utility of the method for human proteins by identifying known and previously unidentified interacting partners of LYN kinase, patient autoantibodies, and the small-molecules gefitinib and dasatinib.

Retrospective analysis of the tolerability and activity of lacosamide in patients with brain tumors: clinical article.

Object: The object of this study was to determine the tolerability and activity of lacosamide in patients with brain tumors.

Methods: The authors reviewed the medical records at 5 US academic medical centers with tertiary brain tumor programs, seeking all patients in whom a primary brain tumor had been diagnosed and who were taking lacosamide.

Results: The authors identified 70 patients with primary brain tumors and reviewed seizure frequency and toxicities.

High-resolution mutational profiling suggests the genetic validity of glioblastoma patient-derived pre-clinical models.

Recent advances in the ability to efficiently characterize tumor genomes is enabling targeted drug development, which requires rigorous biomarker-based patient selection to increase effectiveness. Consequently, representative DNA biomarkers become equally important in pre-clinical studies. However, it is still unclear how well these markers are maintained between the primary tumor and the patient-derived tumor models.

47-year-old man with left leg numbness.

A 47-year-old white male with a history of uveitis, hypercalcemia and nephrolithiasis presented with acute onset partial seizure. On exam he had decreased sensation to light touch on his left lower extremity. A Brain MRI revealed a right frontal mass, which was initially thought to be a metastatic lesion or a primary brain tumor.

Spatial and temporal variation and hotspot detection of kala-azar disease in Vaishali district (Bihar), India.

Background: An improved understanding in transmission variation of kala-azar is fundamental to conduct surveillance and implementing disease prevention strategies. This study investigated the spatio-temporal patterns and hotspot detection for reporting kala-azar cases in Vaishali district based on spatial statistical analysis.

Methods: Epidemiological data from the study area during 2007-2011 was used to examine the dynamic space-time pattern of kala-azar outbreaks, and all cases were geocoded at a village level.