Heterogeneity of cancer-initiating cells within glioblastoma.

Malignant gliomas, particularly glioblastoma multiforme (GBM), account for the majority of brain tumors. Their incidence is increasing world wide and they are incurable. Although a transient response to therapy is observed, tumor recurrence is inevitable and occurs within tissue that has received cytotoxic therapy. This suggests that a subpopulation of resistant cells is responsible for tumor regrowth. The treatment of GBMs represents a daunting challenge to clinicians due principally to the lack of effective therapeutic options. One explanation for this is the marked cellular and genetic heterogeneity within and across these types of tumors. Unravelling the cellular composition of gliomas and describing cell lineage relationships are essential for therapeutic breakthroughs. The recent proposal that a small percentage of cells with stem cells characteristics are responsible for tumor initiation and growth has sparked an interest in applying approaches used to study somatic stem cells toward an understanding of the cellular elements responsible for cancer progression and recurrence. To outline the relevance of these findings is the purpose of this review

Reality check: Asynchronous instruction works!

Never before had I asked a student to cite an emoticon. In traditional classroom instruction, it is unlikely that this would have come up at all. However, in an asynchronous course, you never know where an online threaded discussion on citation formats will lead. As library educators, we have the opportunity to have an impact on a student\u27s chances for success in locating and managing information. We must draw upon the students\u27 familiarity with new technologies and teach them how to effectively articulate their information need, identify appropriate resources, evaluate what has been retrieved, and redirect their continued searching. The challenge that confronts us is compounded by the fact that many students enter the library only through a virtual door. In recognition of the shifting paradigm involving information and new technologies, Purdue University\u27s Electrical Engineering Technology (EET) program asked the Purdue Libraries to develop a credit course that would teach the students how to effectively locate, evaluate, and present information. The course, Information Strategies, has been a required course in EET was designed and taught by the libraries\u27 faculty since 1993. It has subsequently been adapted to other disciplines, as well. As evolution of new technologies continued, course instructors proposed the development of an asynchronous version of this course to the Indiana Higher Education Telecommunications System (IHETS). The development grant was awarded and the first Web-based version of this course was offered Spring 1999. The purpose of the IHETS course development grant was to enhance and convert [the Information Strategies course] to a digital format, which will allow asynchronous statewide access. In July 1998, the investigators, Professors Sheila Curl, Leslie Reynolds, Brent Mai, and Alexius Smith, began adapting the traditional course for delivery over the Internet

Scalable Production of Glioblastoma Tumor-initiating Cells in 3 Dimension Thermoreversible Hydrogels

There is growing interest in developing drugs that specifically target glioblastoma tumor-initiating cells (TICs). Current cell culture methods, however, cannot cost-effectively produce the large numbers of glioblastoma TICs required for drug discovery and development. In this paper we report a new method that encapsulates patient-derived primary glioblastoma TICs and grows them in 3 dimension thermoreversible hydrogels. Our method allows long-term culture (~50 days, 10 passages tested, accumulative ~\u3e1010-fold expansion) with both high growth rate (~20-fold expansion/7 days) and high volumetric yield (~2.0 × 107 cells/ml) without the loss of stemness. The scalable method can be used to produce sufficient, affordable glioblastoma TICs for drug discovery

Scalable Production of Glioblastoma Tumor-initiating Cells in 3 Dimension Thermoreversible Hydrogels

There is growing interest in developing drugs that specifically target glioblastoma tumor-initiating cells (TICs). Current cell culture methods, however, cannot cost-effectively produce the large numbers of glioblastoma TICs required for drug discovery and development. In this paper we report a new method that encapsulates patient-derived primary glioblastoma TICs and grows them in 3 dimension thermoreversible hydrogels. Our method allows long-term culture (~50 days, 10 passages tested, accumulative ~\u3e1010-fold expansion) with both high growth rate (~20-fold expansion/7 days) and high volumetric yield (~2.0 × 107 cells/ml) without the loss of stemness. The scalable method can be used to produce sufficient, affordable glioblastoma TICs for drug discovery

Differential patterns of activity and functional connectivity in emotion processing neural circuitry to angry and happy faces in adolescents with and without suicide attempt

Background - Neural substrates of emotion dysregulation in adolescent suicide attempters remain unexamined. Method - We used functional magnetic resonance imaging to measure neural activity to neutral, mild or intense (i.e. 0%, 50% or 100% intensity) emotion face morphs in two separate emotion-processing runs (angry and happy) in three adolescent groups: (1) history of suicide attempt and depression (ATT, n = 14); (2) history of depression alone (NAT, n = 15); and (3) healthy controls (HC, n = 15). Post-hoc analyses were conducted on interactions from 3 group × 3 condition (intensities) whole-brain analyses (p < 0.05, corrected) for each emotion run. Results - To 50% intensity angry faces, ATT showed significantly greater activity than NAT in anterior cingulate gyral–dorsolateral prefrontal cortical attentional control circuitry, primary sensory and temporal cortices; and significantly greater activity than HC in the primary sensory cortex, while NAT had significantly lower activity than HC in the anterior cingulate gyrus and ventromedial prefrontal cortex. To neutral faces during the angry emotion-processing run, ATT had significantly lower activity than NAT in the fusiform gyrus. ATT also showed significantly lower activity than HC to 100% intensity happy faces in the primary sensory cortex, and to neutral faces in the happy run in the anterior cingulate and left medial frontal gyri (all p < 0.006,corrected). Psychophysiological interaction analyses revealed significantly reduced anterior cingulate gyral–insula functional connectivity to 50% intensity angry faces in ATT v. NAT or HC. Conclusions - Elevated activity in attention control circuitry, and reduced anterior cingulate gyral–insula functional connectivity, to 50% intensity angry faces in ATT than other groups suggest that ATT may show inefficient recruitment of attentional control neural circuitry when regulating attention to mild intensity angry faces, which may represent a potential biological marker for suicide risk

Determination of Somatic and Cancer Stem Cell Self-Renewing Symmetric Division Rate Using Sphere Assays

Representing a renewable source for cell replacement, neural stem cells have received substantial attention in recent years. The neurosphere assay represents a method to detect the presence of neural stem cells, however owing to a deficiency of specific and definitive markers to identify them, their quantification and the rate they expand is still indefinite. Here we propose a mathematical interpretation of the neurosphere assay allowing actual measurement of neural stem cell symmetric division frequency. The algorithm of the modeling demonstrates a direct correlation between the overall cell fold expansion over time measured in the sphere assay and the rate stem cells expand via symmetric division. The model offers a methodology to evaluate specifically the effect of diseases and treatments on neural stem cell activity and function. Not only providing new insights in the evaluation of the kinetic features of neural stem cells, our modeling further contemplates cancer biology as cancer stem-like cells have been suggested to maintain tumor growth as somatic stem cells maintain tissue homeostasis. Indeed, tumor stem cell's resistance to therapy makes these cells a necessary target for effective treatment. The neurosphere assay mathematical model presented here allows the assessment of the rate malignant stem-like cells expand via symmetric division and the evaluation of the effects of therapeutics on the self-renewal and proliferative activity of this clinically relevant population that drive tumor growth and recurrence

Scalable Culturing of Primary Human Glioblastoma Tumor- Initiating Cells with a Cell-Friendly Culture System

Glioblastoma is the most aggressive and deadly brain cancer. There is growing interest to develop drugs that specifically target to glioblastoma tumor-initiating cells (TICs). However, the cost-effective production of large numbers of high quality glioblastoma TICs for drug discovery with current cell culturing technologies remains very challenging. Here, we report a new method that cultures glioblastoma TICs in microscale alginate hydrogel tubes (or AlgTubes). The AlgTubes allowed long-term culturing (~50 days, 10 passages) of glioblastoma TICs with high growth rate (~700-fold expansion/14 days), high cell viability and high volumetric yield (~3.0 × 108 cells/mL) without losing the stem cell properties, all offered large advancements over current culturing methods. This method can be applied for the scalable production of glioblastoma TICs at affordable cost for drug discovery

Scalable Culturing of Primary Human Glioblastoma Tumor- Initiating Cells with a Cell-Friendly Culture System

Glioblastoma is the most aggressive and deadly brain cancer. There is growing interest to develop drugs that specifically target to glioblastoma tumor-initiating cells (TICs). However, the cost-effective production of large numbers of high quality glioblastoma TICs for drug discovery with current cell culturing technologies remains very challenging. Here, we report a new method that cultures glioblastoma TICs in microscale alginate hydrogel tubes (or AlgTubes). The AlgTubes allowed long-term culturing (~50 days, 10 passages) of glioblastoma TICs with high growth rate (~700-fold expansion/14 days), high cell viability and high volumetric yield (~3.0 × 108 cells/mL) without losing the stem cell properties, all offered large advancements over current culturing methods. This method can be applied for the scalable production of glioblastoma TICs at affordable cost for drug discovery

Scalable Culturing of Primary Human Glioblastoma Tumor- Initiating Cells with a Cell-Friendly Culture System

Glioblastoma is the most aggressive and deadly brain cancer. There is growing interest to develop drugs that specifically target to glioblastoma tumor-initiating cells (TICs). However, the cost-effective production of large numbers of high quality glioblastoma TICs for drug discovery with current cell culturing technologies remains very challenging. Here, we report a new method that cultures glioblastoma TICs in microscale alginate hydrogel tubes (or AlgTubes). The AlgTubes allowed long-term culturing (~50 days, 10 passages) of glioblastoma TICs with high growth rate (~700-fold expansion/14 days), high cell viability and high volumetric yield (~3.0 × 108 cells/mL) without losing the stem cell properties, all offered large advancements over current culturing methods. This method can be applied for the scalable production of glioblastoma TICs at affordable cost for drug discovery