COVID-19 infection in patients with late-onset Pompe disease.

Introduction/aims: Severe acute respiratory syndrome coronavirus-2 2019 (SARS-CoV2/COVID-19) is frequently more severe in individuals with pre-existing respiratory and cardiovascular conditions. The impact on patients with neuromuscular disorders is of concern, but remains largely unknown. Late-onset Pompe disease (LOPD) is a lysosomal-storage disorder characterized by progressive skeletal and respiratory muscle degeneration.

Asymmetric cell division promotes therapeutic resistance in glioblastoma stem cells.

Asymmetric cell division (ACD) enables the maintenance of a stem cell population while simultaneously generating differentiated progeny. Cancer stem cells (CSCs) undergo multiple modes of cell division during tumor expansion and in response to therapy, yet the functional consequences of these division modes remain to be determined. Using a fluorescent reporter for cell surface receptor distribution during mitosis, we found that ACD generated a daughter cell with enhanced therapeutic resistance and increased coenrichment of EGFR and neurotrophin receptor (p75NTR) from a glioblastoma CSC.

Therapeutic strategies to induce ERα in luminal breast cancer to enhance tamoxifen efficacy.

Breast cancer is the most prevalent malignancy and second leading cause of death in women worldwide, with hormone receptor-positive luminal breast cancers being the most widespread subtype. While these tumors are generally amenable to endocrine therapy, cellular heterogeneity and acquired ability of tumor cells to undergo cell state switching makes these populations difficult to be fully targeted and eradicated through conventional methods. We have leveraged a quality-by-design (QbD) approach that integrates biological responses with predictive mathematical modeling to identify key combinations of commercially available drugs to induce estrogen receptor expression for therapeutic targeting.

High-Throughput Automated Single-Cell Imaging Analysis Reveals Dynamics of Glioblastoma Stem Cell Population During State Transition.

Cancer stem cells (CSCs) are a heterogeneous and dynamic self-renewing population that stands at the top of tumor cellular hierarchy and contribute to tumor recurrence and therapeutic resistance. As methods of CSC isolation and functional interrogation advance, there is a need for a reliable and accessible quantitative approach to assess heterogeneity and state transition dynamics in CSCs. We developed a high-throughput automated single cell imaging analysis (HASCIA) approach for the quantitative assessment of protein expression with single-cell resolution and applied the method to investigate spatiotemporal factors that influence CSC state transition using glioblastoma (GBM) CSCs (GSCs) as a model system.

Outlining involvement of stem cell program in regulation of O6-methylguanine DNA methyltransferase and development of temozolomide resistance in glioblastoma: An Editorial Highlight for 'Transcriptional control of O -methylguanine DNA methyltransferase expression and temozolomide resistance in glioblastoma' on page 780.

Glioblastoma is a malignant brain tumor that inevitably develops resistance to standard of care drug temozolomide (TMZ) due to a population of cells called cancer stem cells (CSCs). These cells utilize progenitor cell signaling programs and develop robust DNA repair machinery. In this editorial highlight we focus on stem cell regulation of TMZ resistance and discuss findings of Happold et al.

New Advances and Challenges of Targeting Cancer Stem Cells.

The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20-23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop.

CD55 regulates self-renewal and cisplatin resistance in endometrioid tumors.

Effective targeting of cancer stem cells (CSCs) requires neutralization of self-renewal and chemoresistance, but these phenotypes are often regulated by distinct molecular mechanisms. Here we report the ability to target both of these phenotypes via CD55, an intrinsic cell surface complement inhibitor, which was identified in a comparative analysis between CSCs and non-CSCs in endometrioid cancer models. In this context, CD55 functions in a complement-independent manner and required lipid raft localization for CSC maintenance and cisplatin resistance.

Reporter Systems to Study Cancer Stem Cells.

Cancer stem cells have been identified in primary tumors, patient derived xenografts, and established cancer cell lines. The development of reporters has enabled investigators to rapidly enrich for these cells and more importantly track these cells in real time. Here we describe the current state of the reporter field and their use and limitations in multiple cancers.