Induction chemotherapy regimes in first-line treatment for locoregionally advanced nasopharyngeal carcinoma: A network meta-analysis and cost-effectiveness analysis.

OBJECTIVE: The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. PATIENTS AND METHODS: We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. RESULTS: According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. CONCLUSION: Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.

Nano-Bio Interactions: Biofilm-Targeted Antibacterial Nanomaterials.

Biofilm is a spatially organized community formed by the accumulation of both microorganisms and their secretions, leading to persistent and chronic infections because of high resistance toward conventional antibiotics. In view of the tunable physicochemical properties and the related unique biological behavior (e.g., size-, shape-, and surface charge-dependent penetration, protein corona endowed targeting, catalytic- and electronic-related oxidative stress, optical- and magnetic-associated hyperthermia, etc.), nanomaterials-based therapeutics are widely used for the treatment of biofilm-associated infections. In this review, the biological characteristics of biofilm are introduced. And the nanomaterials-based antibacterial strategies are further discussed via biofilm targeting, including preventing biofilm formation, enhancing biofilm penetration, disrupting the mature biofilm, and acting as drug delivery systems. In which, the interactions between biofilm and nanomaterials include mechanical disruption, electron transfer, enzymatic degradation, oxidative stress, and hyperthermia. Additionally, the current advances of nanomaterials for antibacterial nanomaterials by biofilm targeting are summarized. This review aims to present a complete vision of antibacterial nanomaterials-biofilm (nano-bio) interactions, paving the way for the future development and clinical translation of effective antibacterial nanomedicines.

A comprehensive evaluation of circ_0065214/ miR-188-3p/GPNMB axis in breast cancer.

CircRNAs are involved in multiple aspects during carcinogenesis, including tumorigenesis, vascularization, apoptosis and others. Exploring the role of circRNAs in breast cancer (BC) enables us to understand the development mechanism of BC more comprehensively. Here, we screened out and verified an up-regulated circRNA in BC from GEO data. Quantitative Real-time PCR (qRT-PCR) showed that circ_0065214 had a high expression level in BC patients. Besides, circ_0065214 had good diagnostic value in BC serum, and the area under the diagnostic curve, sensitivity and specificity were 0.78, 0.63 and 0.85, respectively. The combined application of circ_0065214 with CEA and CA-153 can further improve the diagnostic efficiency. The knockdown of circ_0065214 in vivo and in vitro inhibited the proliferation, migration and invasion of BC, but promoted autophagy. At last, dual-luciferase reporter assay and rescue assays revealed that circ_0065214 acted as a decoy to adsorb miR-188-3p, and then relieved the repressive effect of miR-188-3p on its target GPNMB. Our results demonstrated that circ_0065214 regulated the expression of GPNMB by competitively binding to miR-188-3p, thus promoting the proliferation, migration and invasion of breast cancer cells and inhibiting autophagy. These findings provided an original therapeutic strategy for BC.

Migrasomes, a new mode of intercellular communication.

Migrasomes are newly discovered extracellular vesicles (EVs) that are formed in migrating cells and mediate intercellular communication. However, their size, biological generation, cargo packaging, transport, and effects on recipient cells by migrasomes are different from those of other EVs. In addition to mediating organ morphogenesis during zebrafish gastrulation, discarding damaged mitochondria, and lateral transport of mRNA and proteins, growing evidence has demonstrated that migrasomes mediate a variety of pathological processes. In this review, we summarize the discovery, mechanisms of formation, isolation, identification, and mediation of cellular communication in migrasomes. We discuss migrasome-mediated disease processes, such as osteoclast differentiation, proliferative vitreoretinopathy, tumor cell metastasis by PD-L1 transport, immune cell chemotaxis to the site of infection by chemokines, angiogenesis promotion via angiogenic factors by immune cells, and leukemic cells chemotaxis to the site of mesenchymal stromal cells. Moreover, as new EVs, we propose the potential of migrasomes for disease diagnosis and treatment. Video Abstract.

Case report: Complete atrio-ventricular block successfully reversed in newly diagnosed primary cardiac B-cell lymphoma.

Primary cardiac tumors are extremely uncommon and primary cardiac lymphoma (PCL) is an even rarer subset. A definite diagnosis can be delayed, which increases the likelihood of a poor prognosis. We report a case involving a 64-year-old male who presented with dyspnea, palpitation, and third-degree atrioventricular block (AVB) secondary to primary cardiac B-cell lymphoma that was diagnosed via endomyocardial biopsy (EMB) and multimodality imaging. Chemotherapy was initiated using rituximab, cyclophosphamide, vindesine, and prednisone (R-COP) followed by implantation of an artificial capsule pacemaker. Third-degree AVB vanished, and the subsequent cycle of treatment was adjusted as R-CDOP (rituximab, cyclophosphamide, doxorubicin liposome, vindesine, and prednisone), with aspirin and rosavastatin to prevent ischemic events. So far, the patient had a good clinical course and normal electrocardiogram. This case underscores the importance of EMB in the diagnosis of heart neoplasms. It is worth noting that anthracycline is not contraindicated in PCL.

Lateral Transfer Learning for Multiagent Reinforcement Learning.

Some researchers have introduced transfer learning mechanisms to multiagent reinforcement learning (MARL). However, the existing works devoted to cross-task transfer for multiagent systems were designed just for homogeneous agents or similar domains. This work proposes an all-purpose cross-transfer method, called multiagent lateral transfer (MALT), assisting MARL with alleviating the training burden. We discuss several challenges in developing an all-purpose multiagent cross-task transfer learning method and provide a feasible way of reusing knowledge for MARL. In the developed method, we take features as the transfer object rather than policies or experiences, inspired by the progressive network. To achieve more efficient transfer, we assign pretrained policy networks for agents based on clustering, while an attention module is introduced to enhance the transfer framework. The proposed method has no strict requirements for the source task and target task. Compared with the existing works, our method can transfer knowledge among heterogeneous agents and also avoid negative transfer in the case of fully different tasks. As far as we know, this article is the first work denoted to all-purpose cross-task transfer for MARL. Several experiments in various scenarios have been conducted to compare the performance of the proposed method with baselines. The results demonstrate that the method is sufficiently flexible for most settings, including cooperative, competitive, homogeneous, and heterogeneous configurations.

Research progress on the roles and mechanisms of γδT cells in periodontitis / 口腔疾病防治

@#Periodontitis is a chronic infectious disease that occurs in periodontal support tissues. Plaque microorganisms are its initiating factor, while local inflammation and alveolar bone loss resulting from periodontitis are the most common causes of tooth loss. Interleukin-17 (IL-17), which plays an important role in the immune response to periodontitis, mostly originates from T helper cell 17 (Th17) and γδT cells. In periodontitis, the role of Th17 cells has been demonstrated broadly, but the role of γδT cells was not revealed until recent years. As a highly heterogeneous group of T lymphocytes, γδT cells are considered a link between innate immunity and adaptive immunity. Studies have found that γδT cells are mostly distributed in the oral epithelium near the biofilm, where they can interact with microorganisms to produce IL-17, recruit neutrophils, macrophages, etc., and participate in the host immune response to periodontitis. They also play a role in the association between periodontitis and relevant systemic diseases. In addition, γδT cells have been proven to produce tissue repair-related factors with a protective effect against periodontitis. The possible mechanism of γδT cells in periodontitis is discussed in this review.

Imbalance of Th17, Treg, and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease involving a variety of immune cells, including adaptive T and B cells and innate lymphoid cells (ILCs). Understanding the pathogenic role of these immune cells in RA provides new insights into the intervention and treatment of RA. METHODS: A total of 86 patients with RA (RA group) and 50 healthy controls (HC) were included in the study. The immune cells of CD4+, CD19+ B, NK, Th17, Treg, ILCs, and their subsets (i.e., ILC1s, ILC2s, and ILC3s) were characterized in peripheral blood mononuclear cells by flow cytometry. Cytokines (i.e., IFN-γ, IL-4, IL-10, IL-17A, IL-22, and IL-33) in sera were detected using ELISA. The above immune cells and cytokines were analyzed in patients with different disease activity status and positive ( +) or negative ( -) rheumatoid factor (RF)/anti-citrullinated protein antibodies (ACPA). RESULTS: Patients with RA had higher percentages of CD4+ T, CD19+ B, Th17, ILC2s, and ILC3s and lower percentages of Treg and ILC1s than HC. Patients with RA had elevated levels of IFN-γ, IL-4, IL-17A, and IL-22 and decreased level of IL-10. Compared with HC, patients with high disease activity had higher percentages of Th17, ILC2s, and ILC3s; lower percentages of ILC1s; and lower level of IL-10. The percentage of Treg cells in remission, low, moderate, and high disease activities decreased, whereas the level of IL-17A increased compared with HC. Furthermore, RF+ or ACPA+ patients exhibited elevated percentages of CD19+ B, ILC2s, and ILC3s and had decreased percentage of ILC1s and Treg cells than HC. The percentage of Th17 cells increased in RF-/ACPA- and RF+/ACPA+ patients. However, the above immune cells between RF or ACPA positive and negative patients were not significantly different. CONCLUSION: Th17, Treg, and ILC subset dysregulations are present in patients with RA but may not be associated with conventionally defined seropositive RF and ACPA. Key Points • Th17, Treg, and ILC subset dysregulations are present in patients with RA but may reflect inflammation rather than specific diseases and stages. • No difference for the distribution of Th17, Treg, and ILC subsets between RF+ and RF- patients and between ACPA+ and ACPA- patients. The screening spectrum of RF and ACPA serology should be expanded to elucidate the role of immune cells in RA pathogenesis.

Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine.

Multidrug resistance (MDR) has become one of the most intractable problems in clinics as it would cause failure in chemotherapy. In this study, we demonstrated that a nanoscale self-assembled nanomedicine, which almost consisted of a pure chemo-drug, could efficiently overcome MDR. Celastrol (CST) was directly assembled into a discrete nanomedicine by precipitation, and then CST nanoparticles (CNPs) inhibited drug efflux pumps by activating HSF-1 expression and promoting HSF-1 translocation into nucleus to suppress the Pgp expression. The more drug accumulated in cells could activate apoptosis signals simultaneously and realize drug resistance reversal. CNPs significantly increased the level of ROS to regulate ERK/JNK signaling, which would further induce resistant cell apoptosis. The tandem apoptosis strategy used the same concentration of CST but achieved a higher antitumor effect. Overall, our study provides a new translational and alternative strategy using conventional natural products to overcome MDR with high efficacy.

Inhibition of BETs prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells.

BACKGROUND: Heat shock response is a protected mechanism against environmental changes for the organism, which must be tightly regulated. Bromodomain and extra terminal-containing protein family (BETs) regulate numerous gene expression in many physiological and pathological conditions, including viral infection. SV40 is considered as a highly human disease-associated virus. OBJECTIVE: We aimed to explore whether BETs play a role in heat shock in SV40 large T antigen transfected cells. METHODS: SV40LTA was transfected in HeLa cells using the Lipofectamine 8000. BETs inhibitor JQ1 and I-BET-762 was employed to treat transfected cells and HEK-293 T cells. Heat shock treatment was performed to determine the effect of JQ1 and I-BET-762 on these cells. Western blot and quantitative RT-PCR were carried out to assess the expression of HSP70 and other HSPs. RESULTS: We found that inhibition of BETs by JQ1 and I-BET-762 protects cells from heat shock-induced death in HEK293T cells. Both JQ1 and I-BET-762 induce the expression of HSPs and HSF1 in HEK-293 T cells. However, neither JQ1 nor I-BET-762 fail to induce the expression of HSPs in either HeLa or HBL-1 cells. When SV40 large T antigen was transfected into HeLa cells, the induction of HSP70 expressing and the protection of heat shock-induced cell death are reproduced by JQ1 and IBET treatment in these transfected cells. CONCLUSIONS: Inhibition of BETs by JQ1 and I-BET-762 prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells. Our data indicate a novel function of BETs in SV40 large T antigen transformed cells, affecting HSPs and HSF1 as well as its function on heat shock response.

Security Analysis of Continuous-Variable Measurement-Device-Independent Quantum Key Distribution Systems in Complex Communication Environments.

Continuous-variable measure-device-independent quantum key distribution (CV-MDI QKD) is proposed to remove all imperfections originating from detection. However, there are still some inevitable imperfections in a practical CV-MDI QKD system. For example, there is a fluctuating channel transmittance in the complex communication environments. Here we investigate the security of the system under the effects of the fluctuating channel transmittance, where the transmittance is regarded as a fixed value related to communication distance in theory. We first discuss the parameter estimation in fluctuating channel transmittance based on these establishing of channel models, which has an obvious deviation compared with the estimated parameters in the ideal case. Then, we show the evaluated results when the channel transmittance respectively obeys the two-point distribution and the uniform distribution. In particular, the two distributions can be easily realized under the manipulation of eavesdroppers. Finally, we analyze the secret key rate of the system when the channel transmittance obeys the above distributions. The simulation analysis indicates that a slight fluctuation of the channel transmittance may seriously reduce the performance of the system, especially in the extreme asymmetric case. Furthermore, the communication between Alice, Bob and Charlie may be immediately interrupted. Therefore, eavesdroppers can manipulate the channel transmittance to complete a denial-of-service attack in a practical CV-MDI QKD system. To resist this attack, the Gaussian post-selection method can be exploited to calibrate the parameter estimation to reduce the deterioration of performance of the system.

Palliative care medical student education: a cross-sectional medical school survey in mainland China.

OBJECTIVE: According to the 2015 Quality of Death Index, China ranks 71st in terms of quality of palliative care out of 80 countries. Lack of palliative care education for health professionals is regarded as largely responsible. The study aims to evaluate the status of palliative care education for medical students in mainland China. METHODS: A list of all medical schools was obtained from the Ministry of Education. A telephone survey of associate deans responsible for medical education at all 282 medical schools in mainland China was conducted in May 2019, following a standardised protocol. Telephone interviews focused on attitudes to palliative care teaching and the extent and manner in which palliative care is incorporated into the curriculum. RESULTS: Associate deans from 173 (61.2%) of the 282 medical schools responded. A total of 120 schools (42.5%) completed the interview, while 53 (18.7%) evaded direct questions related to palliative care. Of the responding deans, 92 (76.7%) regarded palliative care education as very important. However, only 11 (9.2%) provided specific teaching on palliative care. A few schools (n=18) integrated palliative care education within required curricula, such as medical ethics and nursing science. The main reason reported for not providing palliative care education was that the medical curriculum dictated by the Ministry of Education does not require it. CONCLUSION: A very small minority of medical schools in mainland China have any formal teaching about palliative care. Clearly, national standards for didactic and clinical teaching in palliative care for medical students and other health professionals are needed.

SJMHE1 Peptide from Schistosoma japonicum Inhibits Asthma in Mice by Regulating Th17/Treg Cell Balance via miR-155.

PURPOSE: Helminths and their products can regulate immune response and offer new strategies to control and alleviate inflammation, including asthma. We previously found that a peptide named as SJMHE1 from Schistosoma japonicum can suppress asthma in mice. This study mainly investigated the molecular mechanism of SJMHE1 in inhibiting asthma inflammation. METHODS: SJMHE1 was administered to mice with OVA-induced asthma via subcutaneous injection, and its effects were detected by testing the airway inflammation of mice. The Th cell distribution was analyzed by flow cytometry. Th-related transcription factor and cytokine expression in the lungs of mice were analyzed using quantitative real-time PCR (qRT-PCR). The expression of miR-155 and levels of phosphorylated STAT3 and STAT5 were also determined after SJMHE1 treatment in mice by qRT-PCR and Western blot analysis. The in vitro mouse CD4+ T cells were transfected with lentivirus containing overexpressed or inhibited miR-155, and the proportion of Th17, Treg cells, CD4+p-STAT3+, and CD4+p-STAT5+ cells were analyzed by flow cytometry. RESULTS: SJMHE1 ameliorated the airway inflammation of asthmatic mice, upregulated the proportion of Th1 and Treg cells, and the expression of Th1 and Treg-related transcription factor and cytokines. Simultaneously, SJMHE1 treatment reduced the percentage of Th2 and Th17 cells and the expression of Th2 and Th17-related transcription factor and cytokines. SJMHE1 treatment decreased the expression of miR-155 and p-STAT3 but increased p-STAT5 expression. In vitro, the percentage of Th17 and CD4+p-STAT3+ cells increased in CD4+ T cells transfected over-expression of miR-155, but SJMHE1 inhibited the miR-155-mediated increase of Th17 cells. Furthermore, SJMHE1 increased the proportion of Treg and CD4+p-STAT5+ cells after transfected over-expression or inhibition of miR-155. CONCLUSION: SJMHE1 regulated the balance of Th17 and Treg cells by modulating the activation of STAT3 and STAT5 via miR-155 in asthma. SJMHE1 might be a promising treatment for asthma.

miR-370-3p as a Novel Biomarker Promotes Breast Cancer Progression by Targeting FBLN5.

miRNAs play a crucial part in multiple biological processes of cell proliferation, migration, apoptosis, and chemoresistance. In cancer, miRNAs can be divided into oncogenes or tumor suppressors on the basis of their functions in the carcinogenic process. The purpose of this study was to explore the roles and clinical diagnostic value of miR-370-3p in breast cancer. Our results demonstrated that miR-370-3p significantly promoted proliferation, metastasis, and stemness of breast cancer in vitro and in vivo. In particular, clinical data revealed that high expression of serum miR-370-3p and exosomal miR-370-3p from breast cancer patients was remarkably correlated with lymphatic metastasis and tumor node metastasis (TNM) stages. Mechanistically, miR-370-3p inhibited FBLN5 expression and activated the NF-κB signaling pathway to promote breast cancer cell proliferation, migration, and stemness. FBLN5 expression was significantly decreased in breast cancer cells and tumor tissues of breast cancer patients. Our research identified that miR-370-3p promoted breast cancer progression by inhibiting FBLN5 expression and activating the NF-κB signaling pathway. Serum exosomal miR-370-3p would provide a potential biomarker for the diagnosis of breast cancer.

Quantum Hacking on an Integrated Continuous-Variable Quantum Key Distribution System via Power Analysis.

In quantum key distribution (QKD), there are some security loopholes opened by the gaps between the theoretical model and the practical system, and they may be exploited by eavesdroppers (Eve) to obtain secret key information without being detected. This is an effective quantum hacking strategy that seriously threatens the security of practical QKD systems. In this paper, we propose a new quantum hacking attack on an integrated silicon photonic continuous-variable quantum key distribution (CVQKD) system, which is known as a power analysis attack. This attack can be implemented by analyzing the power originating from the integrated electrical control circuit in state preparation with the help of machine learning, where the state preparation is assumed to be perfect in initial security proofs. Specifically, we describe a possible power model and show a complete attack based on a support vector regression (SVR) algorithm. The simulation results show that the secret key information decreases with the increase of the accuracy of the attack, especially in a situation with less excess noise. In particular, Eve does not have to intrude into the transmitter chip (Alice), and may perform a similar attack in practical chip-based discrete-variable quantum key distribution (DVQKD) systems. To resist this attack, the electrical control circuit should be improved to randomize the corresponding power. In addition, the power can be reduced by utilizing the dynamic voltage and frequency scaling (DVFS) technology.

Genomic mutations in patients with advanced non-small cell lung cancer in Yunan and its clinical significance / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the lung cancer-associated driver gene mutations in peripheral blood of patients with advanced non-small cell lung cancer (NSCLC) in Yunnan area, and to explore their association with clinical pathological features. Methods: Peripheral blood of 304 patients with stage Ⅳ NSCLC were collected from Molecular Diagnostic Center of Yunnan Cancer Hospital during January 2019 to December 2019. Next generation sequencing (NGS) technique was used to detect the mutation of NSCLC related driver genes, chi-square test was used to analyze the relationship between the major mutant genes and the clinicopathological features of patients, and Logistic regression was used to analyze the independent risk factors. Results: In the peripheral blood of 304 patients with stage Ⅳ NSCLC, there were 120 (39.47%) cases with EGFR mutations, 12 (3.95%) cases with ALK fusion, 36 (11.84%) case with other mutations such as KRAS, BRAF and RET. The main EGFR mutations were 19del and L858R (69.17%). The mutation rate of EGFR was higher in female, young, non-smoking, non-chemotherapy and lung adenocarcinoma patients (49.26% vs 31.55%, 45.39% vs 33.56%, 45.92% vs 27.78%, 45.07% vs 26.37%, 42.39% vs 10.71%, all P<0.05). Multivariate analysis showed that female, no history of chemotherapy and lung adenocarcinoma were independent risk factors for EGFR mutations (all P<0.05). Conclusion: Using NGS technology to detect the driver genes in peripheral blood of patients with advanced NSCLC in Yunnan area showed that the mutation rate of EGFR was higher in women and lung adenocarcinoma patients without chemotherapy history.

Exosomes: A rising star in breast cancer (Review).

Exosomes are nano­sized extracellular vesicles composed of lipid bilayers. They originate from different types of cells and contain various biological molecules. Exosomes can release their contents and exert their corresponding biological functions. In addition, exosomes play important roles in clinical applications. Exosomes and their contents play key roles in the development of breast cancer, including promoting tumorigenesis, metastasis, angiogenesis, immune escape, and treatment resistance. Exosomes can also be used as biomarkers for cancer diagnosis, prognosis and treatment. In this review, we propose that exosomes are important in clinical applications for breast cancer and their roles cannot be neglected.

Exosomal miR-1910-3p promotes proliferation, metastasis, and autophagy of breast cancer cells by targeting MTMR3 and activating the NF-κB signaling pathway.

Exosomes are key mediators of intercellular communication and play a role in the pathogenesis and progression of cancer. Exosomes in circulating body fluids serve as molecular markers for cancer diagnosis. This study aimed to investigate the role of exosomal microRNA (miR)-1910-3p in breast cancer and determine its clinical diagnostic value. MiR-1910-3p promoted proliferation and migration of breast cancer cells in vitro and in vivo. In vitro, exosomes enriched in miR-1910-3p transferred miR-1910-3p to mammary epithelial cells and breast cancer cells, promoting proliferation and migration, inhibiting apoptosis, and inducing autophagy. In vivo, exosomes enriched in miR-1910-3p promoted the proliferation and migration of breast cancer cells. MiR-1910-3p downregulated myotubularin-related protein 3, activated the NF-κB and wnt/ß-catenin signaling pathway, and promoted breast cancer progression. Serum miR-1910-3p in exosomes was an effective diagnostic marker that improved the sensitivity of breast cancer diagnosis when used in combination with the traditional tumor marker CA153. In conclusion, breast cancer cell-derived exosomes promoted the growth, metastasis, and autophagy of breast cancer cells by transferring miR-1910-3p. MiR-1910-3p in serum exosomes may serve as a novel molecular marker for breast cancer diagnosis.

Mouse bone marrow mesenchymal stem cells with distinct p53 statuses display differential characteristics.

Mesenchymal stem cells (MSCs) affect diverse aspects of tumor progression, such as angiogenesis, tumor growth and metastasis. Bone marrow MSCs (BM­MSCs) are fibroblast­like cells with multipotent differentiation ability, that localize to areas of tissue damage, including wounds and solid tumors. The tumor suppressor gene, p53, is functionally involved in cell cycle control, apoptosis and genomic stability, and is mutated and inactivated in most human cancers. The present study aimed to investigate the role of p53 in the biology of BM­MSCs. In the present study, p53 wild­type (p53+/+), knockdown (p53+/­) and knockout (p53­/­) mouse BM­MSCs (mBM­MSCs) were observed to be similar in appearance and in the expression of cell surface biomarkers, but expressed differential p53 protein levels. The p53+/­ and p53­/­ mBM­MSCs demonstrated an increased proliferation rate compared with mBM­MSCs derived from p53+/+ mice. mBM­MSCs from all three groups, representing distinct p53 statuses, were unable to form tumors over a 3­month period in vivo. The adipogenic and osteogenic differentiation of mBM­MSCs was increased in the absence of p53. The colony formation and migratory abilities of p53+/­ and p53­/­ mBM­MSCs were markedly enhanced, and the expression levels of stem cell­associated proteins were significantly increased compared with p53+/+. The expression levels of microRNA (miR)­3152 and miR­337 were significantly increased in p53+/­ and p53­/­ mBM­MSCs, whereas the expression levels of miR­221, miR­155, miR­1288 and miR­4669 were significantly decreased. The expression levels of tumor necrosis factor­α and interferon­Î³­inducible protein­10 were significantly upregulated in the supernatant of p53+/­ and p53­/­ mBM­MSCs. Ubiquitin protein ligase E3 component n­recognin 2, RING­finger protein 31 and matrix metalloproteinase 19 were highly expressed in p53+/­ and p53­/­ mBM­MSCs. The results of the present study indicated that p53 may serve an important role in the biology of mBM­MSCs, and may provide novel insights into the role of cells with different p53 statuses in cancer progression.

Exosomal TRIM3 is a novel marker and therapy target for gastric cancer.

BACKGROUND: Exosomes are critically involved in cancer development and progression. The exosomal contents have been suggested as ideal cancer biomarkers. In this study, we investigated the expression of exosomal proteins in the serum of gastric cancer patients and their roles in gastric cancer. METHODS: The proteomic profile of exosomes from the serum of gastric cancer patients was detected by using LC-MS/MS. The expression of TRIM3 in exosomes from the serum of gastric cancer patients and healthy controls was assessed by ELISA and western blot. Immunohistochemistry was used to detect TRIM3 expression in gastric cancer tissues and their matching adjacent tissues. The growth and migration abilities of gastric cancer cells with TRIM3 overexpression or knockdown in vitro were evaluated by colony formation assay and transwell migration assay. The effects of TRIM3 overexpression or knockdown on gastric cancer growth and metastasis in vivo were investigated by using subcutaneous xenograft tumor and peritoneal metastasis mouse model. The effects of TRIM3-overexpressing exosomes on gastric cancer growth and metastasis in vitro and in vivo were also evaluated. RESULTS: We found that the expression levels of TRIM3 mRNA and protein were decreased in gastric cancer tissues compared to the matched control tissues. In addition, the levels of TRIM3 protein in the serum exosomes of gastric cancer patients were lower than that in healthy controls. We demonstrated that TRIM3 overexpression reduced while TRIM3 knockdown promoted the growth and metastasis of gastric cancer in vitro and in vivo through the regulation of stem cell factors and EMT regulators. Moreover, exosomes-mediated delivery of TRIM3 protein could suppress gastric cancer growth and metastasis in vitro and in vivo. CONCLUSIONS: Taken together, our findings suggest that exosomal TRIM3 may serve as a biomarker for gastric cancer diagnosis and the delivery of TRIM3 by exosomes may provide a new avenue for gastric cancer therapy.