Cost-Effectiveness and Budget Impact Analysis of Apatinib for Advanced Metastatic Gastric Cancer from the Perspective of Health Insurance System

Objective. This study evaluated the cost-effectiveness of apatinib in patients with chemotherapy-refractory mGC. Patients and Methods. A Markov model was developed to simulate the clinical course of typical patients with chemotherapy-refractory metastatic gastric cancer (mGC). We estimated the 10-year quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratios (ICER). Model inputs were derived from the published literature and government sources. Direct costs were estimated from the perspective of the Chinese health insurance system. A scenario analysis for a Patient Assistance Programme (PAP) was performed. Results. Baseline analysis showed that apatinib increased the cost and QALYs by $7859 and 0.192, respectively, relative to conventional chemotherapy, resulting in an ICER of$40,997/QALY gained. When PAP was available, the ICER was $21,132/QALY. Probabilistic sensitivity analyses confirmed that apatinib with PAP achieved nearly 65$22,200. One-way sensitivity analyses demonstrated that the utility of progression-free survival was the most influential factor on the robustness of the model. Budget impact analysis estimated that the annual increase in fiscal expenditures would be approximately 0.45 million dollars. Conclusions. Our analysis suggests that apatinib is likely cost-effective in patients with chemotherapy-refractory mGC when PAP is available

Subgroup Economic Analysis for Glioblastoma in a Health Resource-Limited Setting

BACKGROUND: The aim of this research was to evaluate the economic outcomes of radiotherapy (RT), temozolomide (TMZ) and nitrosourea (NT) strategies for glioblastoma patients with different prognostic factors. METHODOLOGY/PRINCIPAL FINDINGS: A Markov model was developed to track monthly patient transitions. Transition probabilities and utilities were derived primarily from published reports. Costs were estimated from the perspective of the Chinese healthcare system. The survival data with different prognostic factors were simulated using Weibull survival models. Costs over a 5-year period and quality-adjusted life years (QALYs) were estimated. Probabilistic sensitivity and one-way analyses were performed. The baseline analysis in the overall cohort showed that the TMZ strategy increased the cost and QALY relative to the RT strategy by $25,328.4 and 0.29, respectively; and the TMZ strategy increased the cost and QALY relative to the NT strategy by$23,906.5 and 0.25, respectively. Therefore, the incremental cost effectiveness ratio (ICER) per additional QALY of the TMZ strategy, relative to the RT strategy and the NT strategy, amounts to $87,940.6 and$94,968.3, respectively. Subgroups with more favorable prognostic factors achieved more health benefits with improved ICERs. Probabilistic sensitivity analyses confirmed that the TMZ strategy was not cost-effective. In general, the results were most sensitive to the cost of TMZ, which indicates that better outcomes could be achieved by decreasing the cost of TMZ. CONCLUSIONS/SIGNIFICANCE: In health resource-limited settings, TMZ is not a cost-effective option for glioblastoma patients. Selecting patients with more favorable prognostic factors increases the likelihood of cost-effectiveness

The Heterogeneity of Neutrophil Recruitment in the Tumor Microenvironment and the Formation of Premetastatic Niches

The recruitment of neutrophil to the primary cancer has been shown to be steered by neoplastic cells or tumor-educated mesenchymal stromal cells and has a prometastatic effect. However, the neutrophil chemotaxis and their interaction with tumor cells in the distal metastasized tissues remain elusive. In this review, we discussed emerging research on the interaction between neutrophil recruitment and tumor metastasis, which is essential for studying tumor cell invasion and related immunotherapy

Hypoxia-Regulated lncRNA USP2-AS1 Drives Head and Neck Squamous Cell Carcinoma Progression

The role of hypoxia-regulated long non-coding RNA (lncRNA) in the development of head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. In the current study, we initially screened hypoxia-regulated lncRNA in HNSCC cells by RNA-seq, before focusing on the rarely annotated lncRNA USP2 antisense RNA 1 (USP2-AS1). We determined that USP2-AS1 is a direct target of HIF1α and is remarkably elevated in HNSCC compared with matched normal tissues. Patients with a higher level of USP2-AS1 suffered a poor prognosis. Next, loss- and gain-of-function assays revealed that USP2-AS1 promoted cell proliferation and invasion in vitro and in vivo. Mechanically, RNA pulldown and LC–MS/MS demonstrated that the E3 ligase DDB1- and CUL4-associated factor 13 (DCAF13) is one of the binding partners to USP2-AS1 in HNSCC cells. In addition, we assumed that USP2-AS1 regulates the activity of DCAF13 by targeting its substrate ATR. Moreover, the knockdown of DCAF13 restored the elevated cell proliferation and growth levels achieved by USP2-AS1 overexpression. Altogether, we found that lncRNA USP2-AS1 functions as a HIF1α-regulated oncogenic lncRNA and promotes HNSCC cell proliferation and growth by interacting and modulating the activity of DCAF13

Synthesis of [B,Al]-EWT-Type Zeolite and Its Catalytic Properties

EWT zeolite belongs to ultra-large pore zeolite with the 10MR and 21MR channels, which has good thermal stability, certain acid strength and good application prospects in petroleum refining and petrochemical reactions. However, EWT zeolite has fewer medium/strong acid sites, especially Brönsted acid sites, which makes it difficult to apply to acid-catalyzed reactions. The regulation of acid amount and distribution was achieved by boron and aluminum substitution into the siliceous framework of EWT. The physico-chemical properties of the samples were characterized by XRD, SEM, N2 adsorption-desorption, XRF, ICP, Py-IR, NH3-TPD and 11B & 27Al & 29Si MAS NMR. The results show that quantities of boron and aluminum elements can occupy the framework of [B,Al]-EWT to increase the density of medium and strong acid centers, with more acidity and Brönsted acid centers than EWT zeolite. In the reaction of glycerol with cyclohexanone, the conversion of the sample (U-90-08-10/U-90-H-HCl) is significantly higher than that of the EWT sample, approaching or exceeding the Beta zeolite. A catalytic activity study revealed a direct correlation between the Brönsted acidic site concentration and the activity of the catalyst. The U-90-08-10-H catalyst was also considerably stable in the catalytic process. This work shows, for the first time, that extra-large pore zeolites can be used in industrial acid-catalytic conversion processes with excellent catalytic performance

Single‐Nucleus Transcriptome Profiling of Locally Advanced Cervical Squamous Cell Cancer Identifies Neural‐Like Progenitor Program Associated with the Efficacy of Radiotherapy

Abstract Radiotherapy is the first‐line treatment for locally advanced cervical squamous cell cancer (CSCC). However, ≈50% of patients fail to respond to therapy and, in some cases, tumors progress after radical radiotherapy. Here, single‐nucleus RNA‐seq is performed to construct high‐resolution molecular landscapes of various cell types in CSCC before and during radiotherapy, to better understand radiotherapy related molecular responses within tumor microenvironment. The results show that expression levels of a neural‐like progenitor (NRP) program in tumor cells are significantly higher after radiotherapy and these are enriched in the tumors of nonresponding patients. The enrichment of the NRP program in malignant cells from the tumors of nonresponders in an independent cohort analyzed by bulk RNA‐seq is validated. In addition, an analysis of The Cancer Genome Atlas dataset shows that NRP expression is associated with poor prognosis in CSCC patients. In vitro experiments on the CSCC cell line demonstrate that downregulation of neuregulin 1 (NRG1), a key gene from NRP program, is associated with decreased cell growth and increased sensitivity to radiation. Immunohistochemistry staining in cohort 3 validated key genes, NRG1 and immediate early response 3 from immunomodulatory program, as radiosensitivity regulators. The findings reveal that the expression of NRP in CSCC can be used to predict the efficacy of radiotherapy

Lipolytic inhibitor G0S2 modulates glioma stem-like cell radiation response

Abstract Background Ionizing radiation (IR) therapy is the standard first-line treatment for newly diagnosed patients with glioblastoma (GBM), the most common and malignant primary brain tumor. However, the effects of IR are limited due to the aberrant radioresistance of GBM. Methods Transcriptome analysis was performed using RNA-seq in radioresistant patient-derived glioma stem-like cells (GSCs). Survival of glioma patient and mice bearing-brain tumors was analyzed by Kaplan–Meier survival analysis. Lipid droplet and γ-H2AX foci-positive cells were evaluated using immunofluorescence staining. Results Lipolytic inhibitor G0/G1 switch gene 2 (G0S2) is upregulated in radioresistant GSCs and elevated in clinical GBM. GBM patients with high G0S2 expression had significantly shorter overall survival compared with those with low expression of G0S2. Using genetic approaches targeting G0S2 in glioma cells and GSCs, we found that knockdown of G0S2 promoted lipid droplet turnover, inhibited GSC radioresistance, and extended survival of xenograft tumor mice with or without IR. In contrast, overexpression of G0S2 promoted glioma cell radiation resistance. Mechanistically, high expression of G0S2 reduced lipid droplet turnover and thereby attenuated E3 ligase RNF168-mediated 53BP1 ubiquitination through activated the mechanistic target of rapamycin (mTOR)-ribosomal S6 kinase (S6K) signaling and increased 53BP1 protein stability in response to IR, leading to enhanced DNA repair and glioma radioresistance. Conclusions Our findings uncover a new function for lipolytic inhibitor G0S2 as an important regulator for GSC radioresistance, suggesting G0S2 as a potential therapeutic target for treating gliomas

Markov diagram of health states and the possible transitions among them during each 1-month cycle.

<p>Markov diagram of health states and the possible transitions among them during each 1-month cycle.</p

The cost-effectiveness acceptability curves for the three first-line strategies for GBM in the overall cohort and the 8 subgroups.

<p>The vertical axes represent the probabilities of cost effectiveness. The horizontal axes represent the willingness-to-pay thresholds to gain 1 additional quality-adjusted life-year (QALY). The bold vertical dashed and solid lines represent the thresholds for China and Shanghai City, respectively.</p