Hyaluronic acid (HA) is abundant in tumor microenvironment and closely associated with invasiveness of glioblastoma (GBM) cells. However, the cellular mechanism underlying HA-rich microenvironment in ...GBM remains unexplored. Here, we show that tumor-associated mesenchymal stem-like cells (tMSLCs) contribute to abundance of hyaluronic acid (HA) in tumor microenvironment through HA synthase-2 (HAS2) induction, and thereby enhances invasiveness of GBM cells. In an autocrine manner, C5a secreted by tMSLCs activated ERK MAPK for HAS2 induction in tMSLCs. Importantly, HA acted as a signaling ligand of its cognate receptor RHAMM for intracellular signaling activation underlying invasiveness of GBM cells. Taken together, our study suggests that tMSLCs contribute to HA-rich proinvasive ECM microenvironment in GBM.
The authors describe three fluorescein-conjugated peptides generated by cell-phage display for use as a diagnostic probes for fluorescent detection and imaging of
Salmonella enteritidis
and
...Salmonella typhimurium
. The authors also designed a polyvalent-directed peptide polymer synthesized with poly-D-lysine and bifunctional succinimidyl 3-(2-pyridyldithio)propionate with an affinity and sensitivity that is higher by more than an order of magnitude compared to single peptides due to multiple binding site interactions. In order to establish a diagnostic system for food poisoning, imaging analysis was performed using fluorescence microscopy. The limit of detection of the diagnostic system based on polyvalent directed peptide interaction is 10
2
colony-forming units per mL for
Salmonella
.
Graphical abstract
Schematic of a fluorescent method for detection and imaging of
Salmonella enteritidis
and
Salmonella typhimurium
by using a fluorescein labeled polyvalent-directed peptide polymer (PDPP) with a high affinity and sensitivity as a diagnostic probe. The system uses a microplate reader and was applied to the detection of food poisoning.
Poor prognosis of glioblastoma (GBM) is attributable to the propensity of tumor cells to infiltrate into the brain parenchyma. Protein kinase C (PKC) isozymes are highly expressed or aberrantly ...activated in GBM. However, how this signaling node translates to GBM cell invasiveness remains unknown. Here, we report that among PKC isoforms, PKCδ is strongly associated with infiltration of GBM cells. Notably, PKCδ enhanced Tyr418 phosphorylation of the non-receptor tyrosine kinase SRC, which in turn activated STAT3 and subsequent NOTCH2 signaling, ultimately leading to GBM cell invasiveness. Furthermore, we showed that PKCδ was aberrantly activated in GBM cells by c-MET, a receptor tyrosine kinase hyperactivated in GBM. In agreement, inhibition either component in the c-MET/PKCδ/SRC/STAT3 signaling axis effectively blocked the NOTCH2 signaling and invasiveness of GBM cells. Taken together, our findings shed a light on the signaling mechanisms behind the constitutive activation of PKCδ signaling in GBM.
Highlights • KRAS promotes invasion through epithelial-mesenchymal transition in breast cancer. • KRAS contributes resistance of breast cancer to radio- and chemo-therapy. • BHP blocks KRAS-induced ...malignant phenotypes in breast cancer. • BHP inhibits the downstream effectors of KRAS signaling, PI3K/AKT and Raf-1/ERK.
Highly resistant tumor cells are hard to treat at low doses of plasma. Therefore, researchers have gained more attention to development of enhancers for plasma therapy. Some enhancers could improve ...the efficacy of plasma towards selectivity of cancer cells damage. In this dataset, we report the application of low doses of PEG-coated gold nanoparticles with addition of plasma treatment. This data consists of the effect of PEG-coated GNP and cold plasma on two solid tumor cell lines T98G glioblastoma and A549 lung adenocarcinoma. Cell proliferation, frequency of cancer stem cell population studies by this co-treatment was reported. Finally, we included in this dataset the effect of co-treatment in vivo, using tumor xenograft nude mice models. The data supplied in this article supports the accompanying publication “Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT” (N. K. Kaushik, N. Kaushik, K. C. Yoo, N Uddin, J. S. Kim, S. J. Lee et al., 2016) 1.
Metastasis of breast cancer is promoted by epithelial–mesenchymal transition (
EMT
). Emerging evidence suggests that
STAT
3 is a critical signaling node in
EMT
and is constitutively activated in ...many carcinomas, including breast cancer. However, its signaling mechanisms underlying persistent activation of
STAT
3 associated with
EMT
remain obscure. Here, we report that
PIM
2 promotes activation of
STAT
3 through induction of cytokines. Activation of
STAT
3 caused an increase in
PIM
2 expression, implicating a positive feedback loop between
PIM
2 and
STAT
3. In agreement, targeting of either
PIM
2,
STAT
3 or
PIM
2‐dependent cytokines suppressed
EMT
‐associated migratory and invasive properties through inhibition of
ZEB
1. Taken together, our findings identify the signaling mechanisms underlying the persistent activation of
STAT
3 and the oncogenic role of
PIM
2 in
EMT
in breast cancer.
Glioma cells with stem cell properties, termed glioma stem-like cells (GSCs), have been linked to tumor formation, maintenance, and progression and are responsible for the failure of chemotherapy and ...radiotherapy. Because conventional glioma treatments often fail to eliminate GSCs completely, residual surviving GSCs are able to repopulate the tumor. Compounds that target GSCs might be helpful in overcoming resistance to anticancer treatments in human brain tumors. In this study, we showed that 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP), a new 2-pyrone derivative, suppressed the maintenance of the GSC population in both a glioma cell line and patient-derived glioma cells. Treatment of GSCs with BHP effectively inhibited sphere formation and suppressed the CD133(+) cell population. Treatment with BHP also suppressed expression of the stemness-regulating transcription factors Sox2, Notch2, and β-catenin in sphere-cultured glioma cells. Treatment of GSCs with BHP significantly suppressed two fundamental characteristics of cancer stem cells: self-renewal and tumorigenicity. BHP treatment dramatically inhibited clone-forming ability at the single-cell level and suppressed in vivo tumor formation. BHP markedly inhibited both phosphoinositide 3-kinase/Akt and Ras/Raf-1/extracellular signal-regulated kinase signaling, which suggests that one or both of these pathways are involved in BHP-induced suppression of GSCs. In addition, treatment with BHP effectively sensitized GSCs to chemotherapy and radiotherapy. Taken together, these results indicate that BHP targets GSCs and enhances their sensitivity to anticancer treatments and suggest that BHP treatment may be useful for treating brain tumors by eliminating GSCs.
Wearable electronics have attracted extensive attentions over the past few years for their potential applications in health monitoring based on continuous data collection and real‐time wireless ...transmission, which highlights the importance of portable powering technologies. Batteries are the most used power source for wearable electronics, but unfortunately, they consist of hazardous materials and are bulky, which limit their incorporation into the state‐of‐art skin‐integrated electronics. Sweat‐activated biocompatible batteries offer a new powering strategy for skin‐like electronics. However, the capacity of the reported sweat‐activated batteries (SABs) cannot support real‐time data collection and wireless transmission. Focused on this issue, soft, biocompatible, SABs are developed that can be directly integrated on skin with a record high capacity of 42.5 mAh and power density of 7.46 mW cm−2 among the wearable sweat and body fluids activated batteries. The high performance SABs enable powering electronic devices for a long‐term duration, for instance, continuously lighting 120 lighting emitting diodes (LEDs) for over 5 h, and also offers the capability of powering Bluetooth wireless operation for real‐time recording of physiological signals for over 6 h. Demonstrations of the SABs for powering microfluidic system based sweat sensors are realized in this work, allowing real‐time monitoring of pH, glucose, and Na+ in sweat.
A stretchable, conformable sweat‐activated battery (SAB) has been developed with high power density (7.46 mW cm−2) and energy capacity (42.5 mAh); it enables lighting 120 lighting emitting diodes (LEDs) for 5 h, and offers enough power to support Bluetooth wireless operation for real‐time recording of physiological signals in state‐of‐art wearable sensors for over 6 h. The SAB is also demonstrated in powering microfluidic system based sweat sensors for real‐time monitoring of pH, glucose, and Na+ in sweat.
Poly(d,l‐lactic‐ co‐glycolic acid) (PLGA) microspheres were prepared by an oil/water emulsion solvent evaporation method to use as an injectable microcarrier for cell delivery. Three different kinds ...of PLGA microspheres having hydrophobic, negatively charged, and positively charged surfaces were prepared. Hydrophobic and negatively charged PLGA microspheres were prepared by using terminally capped and uncapped PLGA polymer, respectively. Positively charged PLGA microspheres were prepared by blending PLGA with PLGA‐g‐poly(l‐lysine) graft copolymer as a surface modifying agent. Bovine chondrocytes were cultured on the three PLGA microspheres under serum conditions to comparatively evaluate cell attachment, cell proliferation, and cell function with respect to surface properties. Positively charged PLGA microspheres showed the highest cell attachment, growth, and function compared to hydrophobic and negatively charged microspheres. Surface‐modified PLGA microspheres can potentially be used as an injectable delivery system for cells into a tissue defect site.
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