Tumor-associated macrophages possess the potential to contribute to cancer progression by modulation of immune function, angiogenesis, and cell metastasis. However, understanding of the chemokine signaling networks that regulate this process is unclear. Here, we demonstrate that treatment of CT26 colon cancer cells with RAW 264.7 macrophage conditioned media induces cancer cell migration, invasion and metastasis. Genetic profiling indicated that chemokines SDF-1[alpha] and VEGF are upregulated in tumor- stimulated macrophages and contribute to tumor cell migration in vitro. Macrophages also showed a robust chemotactic response towards tumor-derived chemokines. Microarray analysis and functional testing revealed CSF-1 as the major chemoattractant for macrophages. In the in vivo CAM model, RAW macrophages localized specifically to the tumor periphery where they were found to increase CT26 tumor growth, microvascular density, vascular disruption, and lung metastasis suggesting these cells home to actively invading areas of the tumor, but not the hypoxic core of the tumor mass. Additionally, hypoxic conditions down-regulated CSF-1 production in several tumor cell lines and decreased macrophage migration in vitro. Taken together our findings suggest that normoxic tumor cells release CSF-1 to recruit macrophages to the tumor periphery where they secrete mitogenic and angiogenic factors that facilitate tumor cell proliferation, invasion and metastasis

Posterior cruciate ligament (PCL) injuries are most commonly associated with multiligamentous knee injuries. Isolated rupture can be treated nonoperatively with bracing, but with concomitant surgical injuries or high-grade instability, operative intervention may be warranted. While historically PCL injuries were surgically managed with open primary repair, contemporary surgical options include arthroscopic primary repair and reconstruction. Appropriate patient selection is critical in avoiding residual laxity following primary repair, and innovations in advanced imaging and arthroscopic technology now allow for identification of suitable patients. In this technical vote, we describe a method for anatomic bundle-specific primary PCL repair with transosseous fixation. The appropriate patient for this procedure has a femoral-sided avulsion of 1 or both PCL bundles, presents with an acute or subacute injury, and has adequate tissue quality for bundle reapproximation to the footprint. This allows for minimally invasive, anatomic restoration of tension for each bundle.

A 34-year-old patient presented with a right orbito-facial mass since childhood, consistent with a congenital arteriovenous (AV) malformation. Prior to presentation, she had multiple incomplete surgical resections and embolizations with N-butyl acetyl acrylate and Onyx-18. The patient reported gradual, progressive vision loss shortly after Onyx-18 embolization. Five months after embolization, she presented with decreased vision, disfigurement and mechanical ptosis relating to a large subcutaneous mass affecting the medial right upper eyelid and forehead. Significant exam findings included a visual acuity of 20/400 (20/60 prior to embolization), an afferent pupillary defect, and optic disc pallor. MRI and angiography revealed a persistent AV malformation with feeders from the ophthalmic artery and an absent choroidal flush to the right eye. Pathology from surgical resection showed a significant foreign body giant cell reaction to the embolization material adjacent to the vessels. We suggest that an incomplete embolization with Onyx-18 may have caused vascular steal syndrome from the ophthalmic artery.

Background

Patient stratification to identify subtypes with different disease manifestations, severity, and expected survival time is a critical task in cancer diagnosis and treatment. While stratification approaches using various biomarkers (including high-throughput gene expression measurements) for patient-to-patient comparisons have been successful in elucidating previously unseen subtypes, there remains an untapped potential of incorporating various genotypic and phenotypic data to discover novel or improved groupings.

Methods

Here, we present HOCUS, a unified analytical framework for patient stratification that uses a community detection technique to extract subtypes out of sparse patient measurements. HOCUS constructs a patient-to-patient network from similarities in the data and iteratively groups and reconstructs the network into higher order clusters. We investigate the merits of using higher-order correlations to cluster samples of cancer patients in terms of their associations with survival outcomes.

Results

In an initial test of the method, the approach identifies cancer subtypes in mutation data of glioblastoma, ovarian, breast, prostate, and bladder cancers. In several cases, HOCUS provides an improvement over using the molecular features directly to compare samples. Application of HOCUS to glioblastoma images reveals a size and location classification of tumors that improves over human expert-based stratification.

Conclusions

Subtypes based on higher order features can reveal comparable or distinct groupings. The distinct solutions can provide biologically- and treatment-relevant solutions that are just as significant as solutions based on the original data.

We report on the successful fabrication of orthomode transducer-coupled transition-edge sensor (TES) bolometer arrays for cosmic microwave background (CMB) polarimetry experiments with the superconductor electronics fabrication facility at SEEQC Inc. Commercial microfabrication foundry could provide increase in detector fabrication throughput for a next-generation CMB experiment, CMB-S4, that would deploy approximately one order of magnitude more detectors than current CMB experiments. We also developed TES bolometers with two TESs in series that have two different superconducting temperatures (Tc) using a superconducting proximity effect between niobium (Nb) and aluminum-manganese (AlMn) alloy. We will discuss the motivation, design considerations, fabrication processes, test results, and how industrial detector fabrication could be a path to fabricate hundreds of detector wafers for future CMB polarimetry experiments and other experiments that require TESs and superconducting RF circuits.

Innovative strategies are needed to generate resources to replicate and sustain proven, community-based health promotion programs. Authors describe how civic-minded university students can conduct such programs while simultaneously gaining skills that make them competitive graduate school applicants.

Few clades of plants have proven as difficult to classify as cacti. One explanation may be an unusually high level of convergent and parallel evolution (homoplasy). To evaluate support for this phylogenetic hypothesis at the molecular level, we sequenced the genomes of four cacti in the especially problematic tribe Pachycereeae, which contains most of the large columnar cacti of Mexico and adjacent areas, including the iconic saguaro cactus (Carnegiea gigantea) of the Sonoran Desert. We assembled a high-coverage draft genome for saguaro and lower coverage genomes for three other genera of tribe Pachycereeae (Pachycereus, Lophocereus, and Stenocereus) and a more distant outgroup cactus, Pereskia We used these to construct 4,436 orthologous gene alignments. Species tree inference consistently returned the same phylogeny, but gene tree discordance was high: 37% of gene trees having at least 90% bootstrap support conflicted with the species tree. Evidently, discordance is a product of long generation times and moderately large effective population sizes, leading to extensive incomplete lineage sorting (ILS). In the best supported gene trees, 58% of apparent homoplasy at amino sites in the species tree is due to gene tree-species tree discordance rather than parallel substitutions in the gene trees themselves, a phenomenon termed "hemiplasy." The high rate of genomic hemiplasy may contribute to apparent parallelisms in phenotypic traits, which could confound understanding of species relationships and character evolution in cacti.

Background

In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies.

Methods

Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated.

Results

A subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values <.01; hazard ratios > 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022).

Conclusions

Our findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.

Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs coexisting in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to divergent bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. Stem Cells 2016;34:1702-1707.