Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.

Methods: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients.

CDK4/6 inhibitor abemaciclib combined with low-dose radiotherapy enhances the anti-tumor immune response to PD-1 blockade by inflaming the tumor microenvironment in Rb-deficient small cell lung cancer.

Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have shown significant activity against several solid tumors by reducing the phosphorylation of the canonical CDK4/6 substrate retinoblastoma (Rb) protein, while the anti-tumor effect of CDK4/6 inhibitors on Rb-deficient tumors is not clear. Most small cell lung cancers (SCLCs) are Rb-deficient and show very modest response to immune checkpoint blockade (ICB) despite recent advances in the use of immunotherapy. Here, we aimed to investigate the direct effect of CDK4/6 inhibition on SCLC cells and determine its efficacy in combination therapy for SCLC.

Stem-like T cells and niches: Implications in human health and disease.

Recently, accumulating evidence has elucidated the important role of T cells with stem-like characteristics in long-term maintenance of T cell responses and better patient outcomes after immunotherapy. The fate of T cells has been correlated with many physiological and pathological human processes. In this review, we described present advances demonstrating that stem-like T (T cells are central players in human health and disease.

ATP-responsive mitochondrial probes for monitoring metabolic processes of glioma stem cells in a 3D model.

The metastatic cascade of cancer stem cells (CSCs) is always accompanied by elevated levels of adenosine triphosphate (ATP) as well as the alterntion of energy metabolism to support their differentiation and migration. Here we propose a 3D microfluidic tumor model coupled with an ATP-responsive mitochondrial probe (AMP) for investigation of metabolic processes of glioma stem cells (GSCs). The 3D tumor model has a middle matrix gel microchannel mimicking the extracellular matrix (ECM), which is sandwiched between a GSC culture chamber and a stimulation chamber.

Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models.

Development of personalized cancer vaccines based on neoantigens has become a new direction in cancer immunotherapy. Two forms of cancer vaccines have been widely studied: tumor-associated antigen (including proteins, peptides, or tumor lysates)-pulsed dendritic cell (DC) vaccines and protein- or peptide-adjuvant vaccines. However, different immune modalities may produce different therapeutic effects and immune responses when the same antigen is used.

Reconstituting Glioma Perivascular Niches on a Chip for Insights into Chemoresistance of Glioma.

In this work, we report the direct diagnosing chemoresistance of glioma stem cells (GSCs) during chemotherapy on a biomimetric microsystem that reconstitutes glioma perivascular niches on a chip. Glioma stem cells and endothelial cells were specially cocultured onto the biomimetric system to precisely control stem cell coculture for the proof-of-principle studies. The expression levels of 6- O-methylguanine was confirmed by mass spectrometer, and Bmi-1 gene was also investigated to uncover the chemoresistance of GSCs.

A dual-functional microfluidic chip for on-line detection of interleukin-8 based on rolling circle amplification.

Interleukin 8 (IL-8), also known as C-X-C motif ligand 8(CXCL8), is a proinflammatory chemokine functioned in neutrophil chemotaxis and activation. And it plays an important role in the process of glioma stem-like cell vascularization in the latest research. Herein, a dual-function microfluidic biosensor based on rolling circle amplification (RCA) was fabricated for cell culture and online IL-8 detection.

The pathological structure of the perivascular niche in different microvascular patterns of glioblastoma.

The perivascular niche is critical for intercellular communication between resident cell types in glioblastoma (GBM), and it plays a vital role in maintaining the glioma stem cell (GSC) microenvironment. It is shown in abundant research that different microvascular patterns exist in GBM; and it can be implied that different microvascular patterns are associated with different pathological structures in the perivascular niche. However, the pathological structure of the perivascular niche is still not clear.

Quantitative determination of VEGF165 in cell culture medium by aptamer sandwich based chemiluminescence assay.

In this work, we have developed a sensitive and selective chemiluminescence (CL) assay for vascular endothelial growth factor (VEGF165) quantitative detection based on two specific VEGF165 binding aptamers (Apt). VEGF is a predominant biomarker in cancer angiogenesis, and sensitive detection method of VEGF are highly demanded for both academic study and clinical diagnosis of multiple cancers. In our experiment, VEGF165 was captured in a sandwich structure assembled by two binding aptamers, one capture aptamer was immobilized on streptavidin-coated magnetic beads (MBs) and another VEGF-binding aptamer was labeled by biotin for further phosphatase conjunction.

Dynamic imaging of MYC and CDKN1A mRNAs as an indicator of cell G1-phase arrest.

The identification of G1-phase arrest requires a dynamic capturing method. In this work, we reported an indicator based on MYC and CDKN1A mRNA imaging to visualize G1-phase cycle arrest. A typical G1-phase arrest imaging is shown as a green-to-red conversion by fluorescence molecular beacons indicating the change as down-regulating of MYC and up-regulating of CDKN1A mRNA.

A DNA-directed covalent conjugation fluorescence probe for in vitro detection of functional matrix metalloproteinases.

Matrix metalloproteinases (MMPs) have been considered to contribute to the progression of tumorigenesis and tumor invasion; MMP-9 in particular, has been regarded as a priority target in cancer treatment due to its massive up-regulation in malignant tissues and its ability to degrade type IV collagen. In this work, we employed a DNA-directed covalent conjugation method to design a fluorescence probe for in vitro detection of functional matrix metalloproteinases, by which a nitrilotriacetic acid (NTA)-modified DNA probe can combine with the Zn in the active site of MMPs, and then a molecule beacon (MB) modified FITC and BHQ1 can open to bond with their complementary base, NTA-modified DNA. We can evaluate the amount of MMPs in the medium according to the fluorescence intensity.

A non-invasive genomic diagnostic method for bladder cancer using size-based filtration and microchip electrophoresis.

Bladder cancer (BC) cells spontaneously exfoliated in the urine of patients with BC. Detection of exfoliated tumor cells has clinical significance in cancer therapy because it would enable earlier non-invasive screening, diagnosis, or prognosis of BC. In this research, a method for analyzing genetic abnormalities of BC cells collected from urine samples was developed.

A comparative study of three different nucleic acid amplification techniques combined with microchip electrophoresis for HPV16 E6/E7 mRNA detection.

Research towards nucleic acid amplification technologies for detection of human papillomavirus (HPV) 16 E6/E7 mRNA was carried out in combination with microchip electrophoresis (MCE). The approaches of nucleic acid sequence based amplification (NASBA), one-step RT-PCR and two-step RT-PCR were successfully developed. NASBA was a simple enzymatic reaction, which directly amplified HPV16 mRNA by isothermal amplification, leaving out the complex and tedious operation.

Assay of multiplex proteins from cell metabolism based on tunable aptamer and microchip electrophoresis.

A simple and rapid method for multiplex protein assay based on tunable aptamer by microchip electrophoresis has been developed. Different lengths of aptamers can modulate the electrophoretic mobility of proteins, allowing the protein molecules to be effectively separated in hydroxyethyl cellulose buffer with 1.00 mM magnesium ion.

High-throughput and automatic typing via human papillomavirus identification map for cervical cancer screening and prognosis.

A novel human papillomavirus (HPV) typing assay for cervical cancer screening and prognosis was developed by the combination of restriction fragment length polymorphism (RFLP) and microchip electrophoresis (MCE) to achieve higher levels of sensitivity and throughput. The detection limit of 2 × 10(2) copies, high sensitivity and typing accuracy on the account of PCR-RFLP-MCE method guarantee the successful diagnosis results of 4-fold higher infection rate over cytologic tests. From clinical samples, eleven kinds of HPV types were identified with a good compatibility degree of over 90%.