Comparative efficacy and safety of targeted therapy and immunotherapy for HER2-positive breast cancer: a systematic review and network meta-analyses.

Background: In recent years, novel therapies targeting specific molecular pathways and immunotherapies have exhibited promising outcomes for treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Our work aimed to assess the effectiveness and safety of these emerging treatment regimens for this disease. Material and methods: We systematically searched databases including PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials their inception to August 2023 to identify relevant randomized controlled trials (RCTs). The quality of eligible RCTs was evaluated with the Cochrane risk-of-bias tool, version 2 (RoB2). Investigated outcomes encompassed progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), and adverse events (AEs). They were expressed as hazard ratio (HR) with 95% conference intervals (CI) or risk ratio (RR) with 95% CI. Results: Our analysis identified a total of 28 RCTs suitable for inclusion in the NMA. Regarding the PFS, all these treatment regimens exhibited comparable effectiveness. In terms of OS, Capecitabine+Trastuzumab, Lapatinib+Trastuzumab and Pyrotinib+Capecitabine exhibited better effect compared to other treatments. Regarding pCR and AEs, all these treatment regimens exhibited comparable effectiveness, especially Lapatinib+Trastuzumab and Pyrotinib+Capecitabine. Conclusion: Our study highlights the prominent role of targeted therapies and immunotherapies in treating HER2-positive breast cancer. The efficacy of trastuzumab-containing regimens was superior to other treatment options, while maintaining a comparable safety profile. Based on these findings, trastuzumab-containing regimens emerge as a preferable and recommended choice in clinical practice for managing HER2-positive breast cancer. Systematic Review Registration: PROSPERO, identifier CRD42023414348.

Extraction, rapid preparation and neuroprotective effect of texasin, a main active constituent from Caragana jubata (Pall.) Poir.

Searching for new anti-ischemic stroke (anti-IS) drugs has always been a hot topic in the pharmaceutical industry. Natural products are an important source of discovering anti-IS drugs. The aim of the present study is to extract, rapidly prepare and explore the neuroprotective effect of texasin, a main active constituent from Caragana jubata (Pall.) Poir., which is a kind of Tibetan medicine with a clear anti-IS effect. The results showed that 95% ethanol was the optimal extraction solvent. A three-step rapid preparation method for texasin was successfully established, with a purity of 99.2%. Texasin at the concentration of 25-100 µM had no effect on the viability of normal cultured PC12 cells; 12.5 and 25 µM texasin could enhance the viability of PC12 cells damaged by oxygen and glucose deprivation/reoxygenation (OGD/R), and their effects are comparable to the positive drug edaravone at the concentration of 50 µM. Compared with the normal group, the expression of Bcl-2 protein in OGD/R-injured PC12 cells was downregulated (p < 0.01), and that of PERK, eIF2α, ATF4, CHOP, Bax and Cleaved caspase-3 proteins were upregulated (p < 0.01, p < 0.001). Compared with the OGD/R group, 25 µM texasin could upregulate the expression of Bcl-2 protein (p < 0.01), and downregulate that of PERK, eIF2α, ATF4, CHOP, Bax and Cleaved caspase-3 proteins (p < 0.01, p < 0.001). The 7-OH and 1-O of texasin formed H-bonds with residues Cys891 of the hinge ß-strand of PERK, which is crucial for kinase inhibitors. The above results suggest that the method established in the present study achieved rapid preparation of high-purity texasin. Texasin might inhibit neuronal apoptosis via the regulation of endoplasmic reticulum stress PERK/eIF2α/ATF4/CHOP signalling pathway to exert a protective effect on OGD/R-injured PC12 cells. Aiding by molecular docking, texasin was assumed to be a potential PERK inhibitor.

Sign-Based Gradient Descent With Heterogeneous Data: Convergence and Byzantine Resilience.

Communication overhead has become one of the major bottlenecks in the distributed training of modern deep neural networks. With such consideration, various quantization-based stochastic gradient descent (SGD) solvers have been proposed and widely adopted, among which signSGD with majority vote shows a promising direction because of its communication efficiency and robustness against Byzantine attackers. However, signSGD fails to converge in the presence of data heterogeneity, which is commonly observed in the emerging federated learning (FL) paradigm. In this article, a sufficient condition for the convergence of the sign-based gradient descent method is derived, based on which a novel magnitude-driven stochastic-sign-based gradient compressor is proposed to address the non-convergence issue of signSGD. The convergence of the proposed method is established in the presence of arbitrary data heterogeneity. The Byzantine resilience of sign-based gradient descent methods is quantified, and the error-feedback mechanism is further incorporated to boost the learning performance Experimental results on the MNIST dataset, the CIFAR-10 dataset, and the Tiny-ImageNet dataset corroborate the effectiveness of the proposed methods.

Chlorogenic acid-chitosan copolymers: Synthesis, characterization and application in O/W emulsions for enhanced ß-carotene stability.

In this study, chlorogenic acid-chitosan (CA-CS) copolymers were prepared with varying Chitosan (CS): chlorogenic acid (CA)ratios and characterized for their water solubility, antioxidant capacity, and emulsions stability. Results showed that CA-CS samples exhibited up to 90.5 % increase in DPPH scavenging efficiency and 20 % increase in hydroxyl radical scavenging efficiency compared to CS alone. CA-CS copolymers used to stabilize oil in water (O/W) emulsions, which were evaluated for their potential in encapsulating and protecting ß-carotene. Microscopic observations revealed homogeneous spherical droplets in stable emulsions, suggesting effective interfacial structures. The selected CA-CS-stabilized O/W emulsions demonstrated encapsulation efficiencies of 74.8 % and 75.26 % for ß-carotene. The CA-CS stabilized O/W emulsions provided the most effective protection against ß-carotene degradation under UV exposure, retaining over 80 % of ß-carotene content after 12 h of testing. These findings indicate that CA-CS-based O/W emulsions show promise as carriers and protectors for bioactive compounds, due to their improved antioxidant capacity, emulsions stability, and protection against degradation.

Evaluation of amidated pectin as fat substitutes for minced chicken breast: Physicochemical properties and edible quality.

An investigation was conducted to assess the gelation characteristics of amino acid amidated pectin and its subsequent influence on the quality of minced chicken breast (MCB) when employed as a lipid substitute. Through experimentation, it was evidenced that amidated pectin, such as glycine amidated pectin (AP@Gly), glutamic amidated pectin (AP@Glu), and lysine amidated pectin (AP@Lys), demonstrated superior viscosity and gelation capacity in comparison to their native pectin (PE) counterpart. In contrast to PE, amidated pectin samples exhibited the potential to form high-strength hydrogels under conditions of minimal restriction. Additionally, evaluations conducted on all samples established that MCB samples enriched with pectin and amidated pectin demonstrated superior water retention capability. Before thermal processing, MCB samples fortified with amidated pectin showcased higher hardness and L* values in comparison to PE and the control group. However, upon thermal processing, no significant divergence was found in the chroma and texture profile analysis (TPA) attributes across all MCB samples, and the electronic tongue sensory evaluation was closely aligned with the control group. This evidence substantiates the effectiveness of amidated pectin samples as viable lipid substitutes in MCB products.

SCH 644343 alleviates ischemic stroke-induced neuroinflammation by promoting microglial polarization via the IL-4/SREBP-1 signaling pathway.

Ischemic stroke (IS), a kind of acute cerebrovascular disease, is one of the most common diseases, and it endangers the lives and health of elderly individuals. Inflammation is a key factor leading to stroke, making it a potential therapeutic target. Previous studies have found that neuroinflammation is closely associated with microglial polarization. Due to the various side effects of current drugs used to treat neuroinflammation, it is important to explore alternative drugs with anti-inflammatory activity for neuroinflammation treatment. In the present study, we investigated the effect of SCH 644343 (SCH), a natural compound, on neuroinflammation induced by IS and explored the mechanism. We found that SCH meliorated the phenotypes of IS in vivo, which was correlated with the increased percentage of infiltrated M2 macrophages in brain after stroke. SCH exerted a significant effect against oxygen-glucose deprivation/reoxygenation (OGD/R) in BV2 cells in vitro by inhibiting M1 microglial polarization and promoting M2 microglial polarization. Furthermore, suppression of SREBP-1 expression by pretreatment with the SREBP-1 inhibitor 25-HC attenuated the effect of SCH on IS in vitro. Taken together, SCH exerts anti-IS effect by promoting microglial polarization via the IL-4/SREBP-1 signaling pathway.

Cost-effectiveness analysis of dostarlimab plus carboplatin-paclitaxel as first-line treatment for advanced endometrial cancer.

Background: A recent phase III clinical trial (NCT03981796) evaluated the efficacy and safety of dostarlimab combined with carboplatin-paclitaxel (DOS-CP) compared to placebo combined with carboplatin-paclitaxel (PLB-CP) as a first-line treatment for advanced endometrial cancer (EC). The NCT03981796 trial demonstrated that DOS-CP significantly improved progression-free survival and overall survival of patients with advanced EC while maintaining an acceptable safety profile. However, DOS-CP is expensive and its cost-effectiveness has not been evaluated. This study aims to evaluate the cost-effectiveness of DOS-CP compared to PLB-CP as a first-line treatment for advanced EC from the perspective of the Chinese healthcare system. Methods: A Markov model with three health states was developed to evaluate the cost-effectiveness of DOS-CP as a first-line treatment for advanced EC. Clinical efficacy data were derived from the NCT03981796 trial, and drug costs were determined based on national tender prices. Other costs and utility values were obtained from published literature. The outcomes assessed included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The robustness of the model was assessed through one-way sensitivity analysis and probabilistic sensitivity analysis. Results: In comparison to PLB-CP, the ICER of DOS-CP was $98,276.61/QALY for the overall population, $53,063.61/QALY for the dMMR subgroup, and $124,088.56/QALY for the pMMR subgroup. All of these ICER values were higher than the willingness-to-pay threshold of $38,201 per QALY. The most important variable that affected the results of the model was the discount rate, the cost of dostarlimab, and the utility value for progressive disease. Conclusion: From the perspective of the Chinese healthcare system, DOS-CP is unlikely to be a cost-effective first-line treatment option for advanced EC.

Cost-effectiveness analysis of transarterial chemoembolization combined with lenvatinib as the first-line treatment for advanced hepatocellular carcinoma.

Purpose: Results from the LAUNCH trial suggest transarterial chemoembolization (TACE) in combination with lenvatinib is significantly more effective than lenvatinib as a first-line treatment option for advanced hepatocellular carcinoma (HCC). However, the cost of TACE is substantial. This study compares the cost-effectiveness of TACE in combination with lenvatinib (TACE-LEN) with that of lenvatinib alone as the first-line treatment for advanced HCC from the perspective of the Chinese healthcare system. Methods: Markov models of different health states were constructed to simulate first-line treatment, disease progression, and survival in patients with advanced HCC. Clinical efficacy was obtained from the LAUNCH trial. The cost of drugs was sourced from national tender prices, and the treatment cost of weight-decreased was obtained from the Fujian Provincial Bureau of Prices. Other costs and utility values were based on the published literature. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) comprised the model output. One-way and probabilistic sensitivity analyses were performed to validate model robustness and subgroup analyses were also conducted. Results: Analysis of the model showed that compared to lenvatinib, TACE-LEN improved effectiveness by 1.60 QALYs at a total cost increase of $48,874.69, with an ICER value of $30,482.13/QALY. A one-way sensitivity analysis found that the progression-free survival utility value per year had the greatest impact on the model. A probabilistic sensitivity analysis showed that TACE-LEN had a 97.9% probability of being cost-effective as the first-line treatment option for advanced HCC compared to lenvatinib when the willingness-to-pay (WTP) value was $38,201/QALY (three times the Chinese GDP per capita in 2022). Subgroup analysis showed that all subgroups of patients preferred TACE-LEN. However, when the WTP threshold was below $30,300/QALY, TACE-LEN is no longer cost-effective. Conclusion: Our study found TACE-LEN to be a cost-effective treatment option for patients with advanced HCC compared to lenvatinib from a Chinese healthcare system perspective, but not so in low-income provinces in China.

Cost-effectiveness analysis of zolbetuximab plus mFOLFOX6 as the first-line treatment for CLDN18.2-positive, HER2-negative advanced gastric or Gastroesophageal Adenocarcinoma.

Background: The SPOTLIGHT trial demonstrated that zolbetuximab plus mFOLFOX6 (ZOL-FO) as a first-line regimen compared with placebo plus mFOLFOX6 (PLB-FO) conferred clinical benefits to patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, due to the high cost of zolbetuximab, whether ZOL-FO is cost-effective compared with PLB-FO is unclear. This study aimed to evaluate the cost-effectiveness of ZOL-FO as a first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma from the perspective of the Chinese healthcare system. Methods: Markov models with three different health states were developed to assess the cost-effectiveness of ZOL-FO as a first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma. Clinical efficacy data were obtained from the SPOTLIGHT trial; the drug's cost was calculated at national bid prices, and other costs and utility values were obtained from the published literature. Outcomes included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The model's robustness was verified using one-way sensitivity and probabilistic sensitivity analyses. Results: The ZOL-FO group gained 1.64 QALYs at $87,746.35, while the PLB-FO group gained 1.23 QALYs at $11,947.81. The ICER for ZOL-FO versus PLB-FO was $185,353.28 per QALY gained. The parameters exerting an important impact on the model results were the price of zolbetuximab, body surface area, and progression-free survival utility. At a willingness-to-pay threshold of $38,201/QALY, ZOL-FO had a 0% probability of cost-effectiveness compared with PLB-FO. Conclusion: From the perspective of the Chinese healthcare system, ZOL-FO is unlikely to be cost-effective as the first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma.

Advances in Ablation or Oxidation Mechanisms and Behaviors of Carbon Fiber-Reinforced Si-Based Composites.

Composites with excellent thermomechanical and thermochemical properties are urgently needed in the aerospace field, especially for structural applications under high-temperature conditions. Carbon fiber-reinforced Si-based composites are considered the most promising potential high-temperature materials due to their excellent oxidation resistance and ablative behaviors, good structural designability, and excellent mechanical properties. The reinforcement of the relevant composites mainly involves carbon fiber, which possesses good mechanical and temperature resistance abilities. In this paper, the ablation behaviors and mechanisms of related composites are reviewed. For carbon fiber-reinforced pure Si-based composites (C/SiM composites), the anti-ablation mechanism is mainly attributed to the continuous glassy SiO2, which inhibits the damage of the substrate. For C/SiM composite doping with refractory metal compounds, the oxides of Si and refractory metal together protect the main substrate from ablation and oxidation. Moreover, in addition to thermochemical damage, thermophysical and thermomechanical behavior severely destroy the surface coating of the substrate.

Preparation of amphoteric double network hydrogels based on low methoxy pectin: Adsorption kinetics and removal of anionic and cationic dyes.

The objective of this research was to devise a functional hydrogel was synthesized using pectin (PE), acrylic acid (AA), dimethyldiallyl ammonium chloride (DC), and polyvinyl alcohol (PVA), designed to adsorb both cationic and anionic dyes concurrently. The low methoxy pectin formed double network hydrogel through chemical and physical crosslinking with AA and PVA respectively. DC is combined into the hydrogel system through copolymerization reaction. Analysis of hydrogel's physicochemical properties was conducted using techniques such as infrared spectroscopy, texture analysis, thermogravimetry, and scanning electron microscopy. Dyes adsorption studies showed that the LP/AA/DC/PVA-2 hydrogel, prepared at the molar ratio of AA to DC of 1:2, exhibited higher adsorption efficiency for methylene blue (MB) and Congo red (CR). Kinetics and isotherms studies indicated that the adsorption behavior conformed to the pseudo-second-order kinetic model and Langmuir isotherm model. By the Langmuir isotherm fitting, the maximum adsorption capacities of MB and CR by LP/AA/DC/PVA-2 were recorded to be 222.65 mg/g and 316.46 mg/g, respectively. The adsorption mechanism is dominated by the hydrogen bonding and electrostatic interactions. Further, the adsorption and desorption experiments demonstrated that LP/AA/DC/PVA-2 hydrogel have excellent reusability.

Light disrupts social memory via a retina-to-supraoptic nucleus circuit.

The formation of social memory between individuals of the opposite sex is crucial for expanding mating options or establishing monogamous pair bonding. A specialized neuronal circuit that regulates social memory could enhance an individual's mating opportunities and provide a parallel pathway for computing social behaviors. While the influence of light exposure on various forms of memory, such as fear and object memory, has been studied, its modulation of social recognition memory remains unclear. Here, we demonstrate that acute exposure to light impairs social recognition memory (SRM) in mice. Unlike sound and touch stimuli, light inhibits oxytocin neurons in the supraoptic nucleus (SON) via M1 SON-projecting intrinsically photosensitive retinal ganglion cells (ipRGCs) and GABAergic neurons in the perinuclear zone of the SON (pSON). We further show that optogenetic activation of SON oxytocin neurons using channelrhodopsin is sufficient to enhance SRM performance, even under light conditions. Our findings unveil a dedicated neuronal circuit through which luminance affects SRM, utilizing a non-image-forming visual pathway, distinct from the canonical modulatory role of the oxytocin system.

The cost-effectiveness of cemiplimab plus chemotherapy as the first-line treatment for advanced non-small cell lung cancer.

Background: The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.) PCT as the first-line treatment for patients with advanced NSCLC from the perspective of the Chinese healthcare system. Methods: We constructed a Markov model to evaluate the cost-effectiveness of CCT as the first-line treatment for patients with advanced NSCLC. The transition probabilities were extracted from the survival data of the EMPOWER-LUNG 3 trial. The drugs' costs were referred from national tender prices, while other model input parameters were derived from the EMPOWER-LUNG 3 trial and published literature. The outcome parameters mainly included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model outcomes. Results: Compared to PCT, in the CCT regimen, an additional $79,667 was spent in terms of the total cost and with an additional 0.31 QALYs, resulting in an ICER value of $253,148/QALY. Sensitivity analysis indicated that the hazard ratio (HR) of OS, the cost of cemiplimab (100 mg), and the HR of PFS, all significantly impacted the model's results. The probability of CCT (vs. PCT) being cost-effective was 0% at a willingness-to-pay threshold of $38,201/QALYs in China. The scenario analysis showed that when the price of cemiplimab was reduced to less than $184.09/100 mg, the CCT regimen could be considered cost-effective as the first-line treatment for patients with advanced NSCLC compared to the PCT. Conclusion: In China, the CCT was not cost-effective as the first-line treatment for patients with advanced NSCLC.

Novel Pickering emulsion gels stabilized solely by phenylalanine amidated pectin: Characterization, stability and curcumin bioaccessibility.

Pickering emulsion gels represent a novel class of non-toxic and biocompatible emulsions, offering extensive applications in the pharmaceutical and food additive sectors. This study delineates the synthesis of Pickering emulsion gels utilizing native and amidated pectin samples. Phenylalanine amidated pectin (AP) was procured via an ultra-low temperature enzyme method, while the control group (LP) adhered to an identical procedure without papain catalysis. Experimental outcomes revealed that the AP Pickering emulsion gel manifested superior stability compared to pectin emulsion samples (PE and LP). The Pickering emulsion gel from 5 % amidated pectin (5AP) retained stability throughout a 14-day emulsion stability assessment. Furthermore, all emulsion samples were evaluated for their capacity to deliver and sustain curcumin within an in vitro digestion simulation. Rheological properties and oil droplet size results indicated that the 5AP Pickering emulsion gel exhibited optimal cream index and emulsion stability, effectively inhibiting premature water-oil stratification within the emulsion and augmenting curcumin bioaccessibility. Within the in vitro digestion simulation, the 5AP Pickering emulsion gel demonstrated the highest curcumin bioaccessibility, measured at 17.96 %.

A Tumor Suppressive Role of CYLD as a Novel Potential DUB of Aurora B in Cervical Cancer.

Background: Cervical cancer is a common leading cause of cancer related to women death worldwide. Cylindromatosis (CYLD) is known as an important tumor suppressor in various human cancers, and a deubiquitination enzyme (DUB) as well. Previously, we identified Skp2 as an E3 ligase of Aurora B ubiquitination, but the DUB of Aurora B still remains unknown. Methods: Aurora B ubiquitination site is identified through in vivo ubiquitination assay. Activity of Aurora B and CENPA was detected by immunoblotting (IB) and immunofluorescence (IF) assay. Protein-to-protein interaction was investigated by immunoprecipitation (IP). Cell chromosome dynamics was monitored by live-cell time-lapse Imaging. Cancer cell proliferation, colony formation, apoptosis, and cell invasion and migration assays were also performed. Protein level was checked by immunohistochemical (IHC) staining in clinical cervical cancer samples. Results: We identified Lysine 115 (K115) as the main Aurora B ubiquitination site for Skp2. We could also detect an interaction of Aurora B with the DUB CYLD. We found that CYLD promoted deubiquitination of Aurora B, and regulated Aurora B activity and function as well. Compared with control, we found it took more time for the cells to finish cell mitosis with CYLD over-expression. Furthermore, we found that CYLD deficiency promoted cervical cancer cell proliferation, colony formation, cell migration and invasion, and inhibited apoptosis instead, whereas it is just opposite with CYLD over-expression. In clinical cervical cancer samples, we showed a negative correlation of CYLD expression with Aurora B activation and histological cancer cell invasion. Furthermore, there was less CYLD abundance and higher Aurora B activity in advanced cancer samples compared with early stage. Conclusions: Our findings uncover CYLD as a novel potential DUB of Aurora B, which inhibits Aurora B activation and its subsequent function in cell mitosis, and also provide more evidence for its tumor suppressor function in cervical cancer.

Bone serves as a transfer station for secondary dissemination of breast cancer.

Metastasis is responsible for the majority of deaths among breast cancer patients. Although parallel polyclonal seeding has been shown to contribute to organ-specific metastasis, in the past decade, horizontal cross-metastatic seeding (metastasis-to-metastasis spreading) has also been demonstrated as a pattern of distant metastasis to multiple sites. Bone, as the most frequent first destination of breast cancer metastasis, has been demonstrated to facilitate the secondary dissemination of breast cancer cells. In this review, we summarize the clinical and experimental evidence that bone is a transfer station for the secondary dissemination of breast cancer. We also discuss the regulatory mechanisms of the bone microenvironment in secondary seeding of breast cancer, focusing on stemness regulation, quiescence-proliferation equilibrium regulation, epigenetic reprogramming and immune escape of cancer cells. Furthermore, we highlight future research perspectives and strategies for preventing secondary dissemination from bone.

Ampelopsin induces MDA-MB-231 cell cycle arrest through cyclin B1-mediated PI3K/AKT/mTOR pathway in vitro and in vivo.

Breast cancer is one of the most common malignant tumors in women and it is the most frequently diagnosed cancer in the world. Ampelopsin (AMP) is a purified component from the root of Ampelopsis grossedentata. It is reported that AMP could significantly inhibit the proliferation of breast cancer cells. However, the antitumor mechanism against breast cancer has not yet been fully elucidated. The purpose of this work was to study the role of AMP against breast cancer MDA-MB-231 cells and to further investigate the underlying mechanism. PI3K/AKT/mTOR plays a very important role in tumor cell growth and proliferation and we hypothesize that AMP may inhibit this pathway. In the present work, the results showed that AMP could significantly inhibit the growth of breast cancer MDA-MB-231 cells in vitro and in vivo. In addition, treatment with AMP decreased the levels of PI3K, AKT and mTOR, as well as cyclin B1 expression, followed by p53/p21 pathway activation to arrest the cell cycle at G2/M. Moreover, it demonstrated a positive association between cyclin B1 and PI3K/AKT/mTOR levels. Importantly, this pathway was found to be regulated by cyclin B1 in MDA-MB-231 cells treated with AMP. Also, it was observed that cyclin B1 overexpression attenuated cell apoptosis and weakened the inhibitory effects of AMP on cell proliferation. Together, AMP could inhibit breast cancer MDA-MB-231 cell proliferation in vitro and in vivo, due to cell cycle arrest at G2/M by inactivating PI3K/AKT/mTOR pathway regulated by cyclin B1.

SHCBP1 Is a Prognostic Biomarker Related to the Tumour Immune Microenvironment in Pan-Cancer.

OBJECTIVE: Shc SH2 domain-binding protein (SHCBP1) is involved in regulating tumour progression in a variety of tumour types. The aim of this study was to analyze the prognostic landscape of SHCBP1 in pan-cancer and investigate the relationship between SHCBP1 expression and tumour immune microenvironment. METHODS: The Cancer Genome Atlas (TCGA) and genotype tissue expression (GTEx) database were used for obtaining the required data for the evaluation of SHCBP1 expression. The clinical characteristics and prognostic role of SHCBP1 were analyzed by using TCGA cohort. This was followed by gene set enrichment analysis by R software. Based on TCGA pan-cancer data, the correlation between SHCBP1 expression and immune infiltration, immune-related genes, microsatellite instability (MSI), and tumour mutational burden (TMB) was discussed. Finally, the half-maximum inhibitory concentration (IC50) values of 192 anti-cancer drugs were obtained from the Genomics of Drug Sensitivity in Cancer (GDSC) database and their correlation with SHCBP1 was analyzed. RESULTS: SHCBP1 was upregulated in most tumours showing a significant association with poor prognosis. Gene set enrichment analysis revealed SHCBP1 relation to the immunity, cell cycle, and cancer pathway in various types of tumour. SHCBP1 expression also showed a positive correlation with tumour-associated macrophages (TAMs) and immunosuppressive genes including TGFBR1, PD-L1 and TGFB1 and so on. In addition, high expression of SHCBP1 in patients was associated with resistance to a variety of anti-tumour drugs. CONCLUSION: The present study confirms SHCBP1 as a poor prognostic marker of cancers. Its high expression is suggested to be involved in immunological resistance to a variety of anti-tumour drugs.

Cost-effectiveness analysis of sintilimab plus chemotherapy for advanced or metastatic esophageal squamous cell carcinoma.

Background: Sintilimab plus chemotherapy (SIDCHM) is more effective than placebo plus chemotherapy (PLCHM) for advanced or metastatic esophageal squamous cell carcinoma (ESCC). However, considering the high cost of sintilimab, this study evaluated the cost-effectiveness of SIDCHM in comparison with PLCHM for advanced or metastatic ESCC from the Chinese healthcare system perspective. Methods: Polymorphic Markov models were constructed to simulate the course and cost of SIDCHM. Treatment drug costs were calculated at national list prices and clinical data, other costs, and utility values were extracted from the reference literature. Primary outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). The robustness of the model was verified by one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: SIDCHM obtained 1.03 QALYs at $24,044.49, whereas the effectiveness and cost of PLCHM were 0.67 QALYs and $14,166.24, respectively. The ICER for SIDCHM versus PLCHM was $23,458.08/QALY. The utility of the PFS state was the parameter that had the greatest effect on the ICER. The PSA showed that SIDCHM had an 86% probability of being cost-effective at the willingness-to-pay threshold of 3* Chinese gross domestic product per capita ($37,653/QALY). Conclusion: From the Chinese healthcare system perspective, SIDCHM is considered a cost-effective treatment option compared with PLCHM as first-line therapy for advanced or metastatic ESCC.

Cost-effectiveness analysis of adebrelimab combined with chemotherapy for extensive-stage small cell lung cancer.

Background: The findings of the CAPSTONE-1 trial showed that adebrelimab in combination with chemotherapy (etoposide-carboplatin) (ADCHM) is clinically beneficial as a first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), compared with placebo plus chemotherapy (PLCHM, etoposide-carboplatin). However, owing to the higher cost of adebrelimab, it is unclear whether ADCHM is cost-effective compared with PLCHM. This study aimed to evaluate the cost-effectiveness of ADCHM as a first-line treatment for patients with ES-SCLC from the perspective of the Chinese healthcare system. Methods: A Markov model with three health states was developed to assess the cost-effectiveness of ADCHM as a first-line treatment option with ES-SCLC. Clinical data were obtained from the CAPSTONE-1 trial. Costs of the drug were calculated at national tender prices, and other costs and utility values were obtained from published literature. The outcomes included life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were used to validate the robustness of the model. Results: The ADCHM group achieved 1.21 QALYs (2.47 LYs) for $25,312, whereas the PLCHM group achieved 0.81 QALYs (1.59 LYs) for $14,846. The ICER for ADCHM versus PLCHM was $25914 per QALY gained. The variables with the greatest impact on the model results were the utility value of progressive disease, the utility value of progression-free survival, and the price of adebrelimab (100 mg). At a willingness-to-pay threshold of $37,653/QALY, ADCHM had an 89.1% probability of being cost-effective compared with PLCHM. Conclusion: ADCHM may be a cost-effective first-line treatment strategy for ES-SCLC from the perspective of the Chinese healthcare system.