Precise identification of somatic and germline variants in the absence of matched normal samples.

Somatic variants play a crucial role in the occurrence and progression of cancer. However, in the absence of matched normal controls, distinguishing between germline and somatic variants becomes challenging in tumor samples. The existing tumor-only genomic analysis methods either suffer from limited performance or insufficient interpretability due to an excess of features.

Mutation-guided chemotherapy-free strategy in first-line immunotherapy for low PD-L1-expressing non-squamous NSCLC.

Background: The necessity of platinum-doublet chemotherapy in first-line immunotherapy for non-squamous non-small cell lung cancer (nsqNSCLC) with programmed death-ligand 1 (PD-L1) expression on less than 50% of tumor cells remains poorly investigated. Biomarkers predicting this necessity can guide chemotherapy-free treatment to minimize unnecessary toxicity.

Methods: Treated with immune checkpoint inhibitor monotherapy (ICI-mono), chemotherapy, or combination (ICI-chemo), 790 low PD-L1-expressing nsqNSCLCs (in-house: n=83; public: n=707) were analyzed for development and validation of the interaction score for additional chemotherapy (ISAC).

An advanced NSCLC patient with and fusions treated with -TKI combination therapy: a case report.

Background: Anaplastic lymphoma kinase () rearrangement is one of the most important drivers in non-small cell lung cancer (NSCLC). Despite the effectiveness to canonical 3'- fusions, the clinical efficacy of ALK inhibitors in patients with complex fusions, such as nonreciprocal/reciprocal translocation remains uncertain. Exploring the optimal therapeutic regimens for this subset of patients is of crucial clinical significance.

Gross Total Resection Promotes Subsequent Recovery and Further Enhancement of Impaired Natural Killer Cell Activity in Glioblastoma Patients.

Glioblastoma is the most common primary malignant brain tumor, and median survival is relatively short despite aggressive standard treatment. Natural killer (NK) cell dysfunction is strongly associated with tumor recurrence and metastasis but is unclear in glioblastoma. NK activity (NKA) represents NK cell-secreted interferon-γ (IFN-γ), which modulates immunity and inhibits cancer progression.

mutation landscape in non-small cell lung cancer patients in Northeast China.

Objective: This study aimed to explore erb-b2 receptor tyrosine kinase 2 () gene mutations in patients with non-small cell lung cancers (NSCLC) in Northeast China, and to analyze mutation subtypes and clinicopathological characteristics related to the presence of mutations.

Methods: In this study, 1087 tissue samples, 368 whole blood samples, and 68 pleural effusion samples from 1349 NSCLC were collected. Next-generation sequencing (NGS) was used to perform genetic testing on the samples.

Colony‑stimulating factor CSF2 mediates the phenotypic plasticity of small‑cell lung cancer by regulating the p‑STAT3/MYC pathway.

Relapse and drug resistance are the main causes of mortality in patients with small‑cell lung cancer (SCLC). Intratumoral heterogeneity (ITH) is a key biological mechanism that leads to relapse and drug resistance. Phenotypic plasticity is an important factor that leads to ITH in SCLC, although its mechanisms and key regulatory factors remain to be elucidated.

Matriptase-2/NR4A3 axis switches TGF-β action toward suppression of prostate cancer cell invasion, tumor growth, and metastasis.

Dysregulation of pericellular proteolysis is strongly implicated in cancer metastasis through alteration of cell invasion and the microenvironment. Matriptase-2 (MT-2) is a membrane-anchored serine protease which can suppress prostate cancer (PCa) cell invasion. In this study, we showed that MT-2 was down-regulated in PCa and could suppress PCa cell motility, tumor growth, and metastasis.

Aberrant Alteration of Circulating Lymphocyte Subsets in Small Cell Lung Cancer Patients Treated with Radiotherapy.

The role of different circulating lymphocyte subsets, as well as their correlation with clinical characteristics of small cell lung cancer patients have not yet been fully understood. This study aims to evaluate the influence of the fluctuating absolute numbers of lymphocyte subpopulations in peripheral blood of patients with small cell lung cancer. The absolute counts and percentages of lymphocyte subsets in peripheral blood of 329 patients with small cell lung cancer were retrospectively analyzed.

Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD.

Current clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8 T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8 T lymphocyte proliferation, and we identify CAD, a key enzyme of pyrimidine biosynthesis, to be a novel afatinib target.

A Novel ROS1-FBXL17 Fusion Co-Existing with CD74-ROS1 Fusion May Improve Sensitivity to Crizotinib and Prolong Progression-Free Survival of Patients with Lung Adenocarcinoma.

Purpose: The rearrangement of (C-ros oncogene 1) is an important driver of non-small cell lung cancer (NSCLC). Currently, only approximately 24 fusion partners have been shown to be sensitive to crizotinib. Although fusion partner determination is not required to treat patients with tyrosine kinase inhibitor, the correlation between phenotypes and efficacies still needs more researches.

Inhibition of TMPRSS2 by HAI-2 reduces prostate cancer cell invasion and metastasis.

TMPRSS2 is an important membrane-anchored serine protease involved in human prostate cancer progression and metastasis. A serine protease physiologically often comes together with a cognate inhibitor for execution of proteolytically biologic function; however, TMPRSS2's cognate inhibitor is still elusive. To identify the cognate inhibitor of TMPRSS2, in this study, we applied co-immunoprecipitation and LC/MS/MS analysis and isolated hepatocyte growth factor activator inhibitors (HAIs) to be potential inhibitor candidates for TMPRSS2.

Author Correction: The Kunitz Domain I of Hepatocyte Growth Factor Activator Inhibitor-2 Inhibits Matriptase Activity and Invasive Ability of Human Prostate Cancer Cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis.

Background: Dysregulation of pericellular proteolysis usually accounts for cancer cell invasion and metastasis. Isolation of a cell-surface protease system for lung cancer metastasis is an important issue for mechanistic studies and therapeutic target identification.

Methods: Immunohistochemistry of a tissue array (n = 64) and TCGA database (n = 255) were employed to assess the correlation between serine protease inhibitors (SPIs) and lung adenocarcinoma progression.

The Kunitz Domain I of Hepatocyte Growth Factor Activator Inhibitor-2 Inhibits Matriptase Activity and Invasive Ability of Human Prostate Cancer Cells.

Dysregulation of pericellular proteolysis is often required for tumor invasion and cancer progression. It has been shown that down-regulation of hepatocyte growth factor activator inhibitor-2 (HAI-2) results in activation of matriptase (a membrane-anchored serine protease), human prostate cancer cell motility and tumor growth. In this study, we further characterized if HAI-2 was a cognate inhibitor for matriptase and identified which Kunitz domain of HAI-2 was required for inhibiting matriptase and human prostate cancer cell motility.

Ketamine Increases Permeability and Alters Epithelial Phenotype of Renal Distal Tubular Cells via a GSK-3β-Dependent Mechanism.

Ketamine, a dissociative anesthetic, is misused and abused worldwide as an illegal recreational drug. In addition to its neuropathic toxicity, ketamine abuse has numerous effects, including renal failure; however, the underlying mechanism is poorly understood. The process called epithelial phenotypic changes (EPCs) causes the loss of cell-cell adhesion and cell polarity in renal diseases, as well as the acquisition of migratory and invasive properties.

Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis.

Dysregulation of androgen signaling and pericellular proteolysis is necessary for prostate cancer progression, but the links between them are still obscure. In this study, we show how the membrane-anchored serine protease TMPRSS2 stimulates a proteolytic cascade that mediates androgen-induced prostate cancer cell invasion, tumor growth, and metastasis. We found that matriptase serves as a substrate for TMPRSS2 in mediating this proinvasive action of androgens in prostate cancer.

Feasibility of human hair follicle-derived mesenchymal stem cells/CultiSpher(®)-G constructs in regenerative medicine.

The use of human mesenchymal stem cells (hMSCs) in cell therapies has increased the demand for strategies that allow efficient cell scale-up. Preliminary data on the three-dimensional (3D) spinner culture describing the potential use of microcarriers for hMSCs culture scale-up have been reported. We exploited a rich source of autologous stem cells (human hair follicle) and demonstrated the robust in vitro long-term expansion of human hair follicle-derived mesenchymal stem cells (hHF-MSCs) by using CultiSpher(®)-G microcarriers.

Large-scale expansion of Wharton's jelly-derived mesenchymal stem cells on gelatin microbeads, with retention of self-renewal and multipotency characteristics and the capacity for enhancing skin wound healing.

Introduction: Successful stem cell therapy relies on large-scale generation of stem cells and their maintenance in a proliferative multipotent state. This study aimed to establish a three-dimension culture system for large-scale generation of hWJ-MSC and investigated the self-renewal activity, genomic stability and multi-lineage differentiation potential of such hWJ-MSC in enhancing skin wound healing.

Methods: hWJ-MSC were seeded on gelatin microbeads and cultured in spinning bottles (3D).

Cyclosporine A increases hair follicle growth by suppressing apoptosis-inducing factor nuclear translocation: a new mechanism.

Cyclosporine A (CsA) enhances hair growth through caspase-dependent pathways by retarding anagen-to-catagen phase transition in the hair follicle growth cycle. Whether apoptosis-inducing factor (AIF), a protein that induces caspase-independent apoptosis, can regulate the hair follicle cycle in response to CsA is currently unclear. Here, we show that the pro-hair growth properties of CsA are in part due to blockage of AIF nuclear translocation.

Engineered hair follicle mesenchymal stem cells overexpressing controlled-release insulin reverse hyperglycemia in mice with type L diabetes.

Genetically engineered stem cells that overexpress genes encoding therapeutic products can be exploited to correct metabolic disorders by repairing and regenerating diseased organs or restoring their function. Hair follicles are readily accessible and serve as a rich source of autologous stem cells for cell-based gene therapy. Here we isolated mesenchymal stem cells from human hair follicles (HF-MSCs) and engineered them to overexpress the human insulin gene and release human insulin in a time- and dose-dependent manner in response to rapamycin.