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Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma

《医学前沿（英文）》 doi: 10.1007/s11684-023-1029-3

摘要： Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

关键词： tumor prognosis molecular Microbiome subsets determine center analysis microbiome transcriptome data

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Relationship of adrenomedullin expression and microvessel density and prognosis in smooth muscle tumor

JIANG Yuan, TIAN Xuehong, YUAN Jie, JIN Yuemei, TAN Yusong

《医学前沿（英文）》 2007年第1卷第4期页码 398-400 doi: 10.1007/s11684-007-0077-4

摘要： The aim of this paper was to investigate the relationship between the expression of adrenomedullin (ADM) and microvessel density (MVD) and prognosis in smooth muscle tumor of uterus. The expression of ADM was detected using immunohistochemical staining in specimens from 15 normal controls, 28 cases of uterine leiomyoma (LE) and 19 cases of uterine leiomyosarcoma (LES). The MVD was assayed by immunostainting with CD. There was a positive correlation between the ADM expression and MVD in LE and LES respectively ( = 0.823, <0.01; = 0.793, <0.01). The expression of ADM in LE was statistically lower than that in LES (<0.05). There was a positive correlation between the ADM expression and mitotic figures in LES (<0.05): the more mitotic figures, the higher levels of the ADM expression and poor prognosis. The ADM is an important angiogenic factor in smooth muscle tumor of uterus. The ADM can be used as an accessory marker in estimating the malignant potency of LE and judging the pro gnosis of LES, and as a novel molecular target of anti-angiogenic and anticarcinogenic strategies.

关键词： anticarcinogenic microvessel density malignant potency muscle uterine leiomyosarcoma

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Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

《医学前沿（英文）》 doi: 10.1007/s11684-023-1050-6

摘要： Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

关键词： pancreatic cancer cancer screening single cell molecular alterations precancerous lesion therapy resistance

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Breast cancer-associated fibroblasts: their roles in tumor initiation, progression and clinical applications

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《医学前沿（英文）》 2016年第10卷第1期页码 33-40 doi: 10.1007/s11684-016-0431-5

摘要：

Breast cancer is the most common malignant tumor in women, and the incidence of this disease has increased in recent years because of changes in diet, living environment, gestational age, and other unknown factors. Previous studies focused on cancer cells, but an increasing number of recent studies have analyzed the contribution of cancer microenvironment to the initiation and progression of breast cancer. Cancer-associated fibroblasts (CAFs), the most abundant cells in tumor stroma, secrete various active biomolecules, including extracellular matrix components, growth factors, cytokines, proteases, and hormones. CAFs not only facilitate the initiation, growth, angiogenesis, invasion, and metastasis of cancer but also serve as biomarkers in the clinical diagnosis, therapy, and prognosis of breast cancer. In this article, we reviewed the literature and summarized the research findings on CAFs in breast cancer.

关键词： cancer-associated fibroblast breast cancer progression prognosis

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利用纳米粒子进行肿瘤分子成像 Review

程震,闫雪峰,孙夕林,申宝忠,Sanjiv Sam Gambhir

《工程（英文）》 2016年第2卷第1期页码 132-140 doi: 10.1016/J.ENG.2016.01.027

摘要：

分子成像不仅可以利用传统成像技术提供结构图像，也可利用许多新的成像技术提供生物功能信息和分子信息。在过去的几十年间，纳米技术在分子成像中的应用显示了许多明显的优势，并且为活体成像提供了新的机遇。多模态纳米粒子可对肿瘤的生物性和微环境做出精确评估。本文讨论了与工程化纳米粒子相关的话题，并总结了近几年来这些纳米结构在恶性肿瘤光学成像、超声成像、光声成像、磁共振成像和放射性核素显像中的应用；同时，还讨论了将纳米粒子应用到临床医学中面临的主要挑战。

关键词：肿瘤分子成像纳米粒子

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Caveolin proteins: a molecular insight into disease

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《医学前沿（英文）》 2016年第10卷第4期页码 397-404 doi: 10.1007/s11684-016-0483-6

摘要：

Caveolae are a kind of specific cystic structures of lipid rafts in the cytoplasmic membrane and are rich in cholesterol and sphingolipids. In recent years, many researchers have found that both caveolins and caveolae play a role in the development of various human diseases, including coronary heart disease, hypertension, and nervous system disorders. The specific mechanisms by which caveolins induce diseases have been a topic of interest. However, a number of detailed molecular mechanisms remain poorly understood. This article focuses on the relationship between caveolin proteins and human diseases and reviews the molecular mechanisms of caveolins in disease networks.

关键词： caveolin caveolae microRNA disease signaling pathway heart tumor

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Translational medicine in hepatocellular carcinoma

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《医学前沿（英文）》 2012年第6卷第2期页码 122-133 doi: 10.1007/s11684-012-0193-7

摘要：

Hepatocellular carcinoma (HCC) is a highly complex disease that is generally resistant to commonly used chemotherapy and radiotherapy. Consequently, there is an urgent need for the development of new treatment strategies for this devastating disease. In the past decade, tremendous progress has been achieved in the molecular stratification of HCCs for diagnosis, prognosis, and therapeutic decision-making. To date, the molecular classification of HCCs has been carried out through transcriptomic, genetic and epigenetic profiling of tumors. Such research has led to identification of several potential molecular targets in HCC, and subsequently, development of novel systemic agents for the treatment of HCC has begun in earnest. In this article, we review the current knowledge of the molecular pathogenesis of HCC and outline potential areas for application of this knowledge in a clinical setting. As a typical virus and inflammation-associated cancer, both host immune response and tumor microenvironment have crucial roles in HCC pathogenesis. In addition, we examine the potential of immunotherapy and strategies targeting various components of the tumor microenvironment, as well as novel molecular and cellular targets in HCC such as cancer stem cells.

关键词： hepatocellular carcinoma molecular classification molecular targeted therapies tumor microenvironment immunotherapy

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Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in hepatocellular carcinoma

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《医学前沿（英文）》 2016年第10卷第1期页码 52-60 doi: 10.1007/s11684-016-0433-3

摘要：

Hepatocellular carcinoma (HCC) is a lethal liver malignancy worldwide. In this study, we reported that protein phosphatase magnesium-dependent 1δ (PPM1D) was highly expressed in the majority of HCC cases (approximately 59%) and significantly associated with high serum α-fetoprotein (AFP) level (P= 0.044). Kaplan-Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor of HCC-specific overall survival (HR, 2.799; 95% CI, 1.346–5.818, P = 0.006). Overexpressing PPM1D promoted cell viability and invasion, whereas RNA interference-mediated knockdown of PPM1D inhibited proliferation, invasion, and migration of cultured HCC cells. In addition, PPM1D suppression by small interfering RNA decreased the tumorigenicity of HCC cells in vivo. Overall, results suggest that PPM1D is a potential prognostic marker and therapeutic target for HCC.

关键词： PPM1D hepatocellular carcinoma prognosis target therapy

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Elevated C-reactive protein levels predict worsening prognosis in Chinese patients with first-onset stroke

Jiangtao YAN, Rutai HUI, Daowen WANG

《医学前沿（英文）》 2009年第3卷第1期页码 30-35 doi: 10.1007/s11684-009-0005-x

摘要： The role of high sensitivity C-reactive protein (hsCRP) in predicting prognosis after stroke in the Asian population has not been investigated. We hypothesized that elevated levels of hsCRP were associated with worsening prognosis after stroke in Chinese patients. Two hundred and ninety consecutive patients with first-onset stroke and 290 age- and gender-matched control subjects without any cerebrovascular disease were enrolled for study. Plasma hsCRP level was detected and subsequent vascular events and death were recorded in both groups over a 5-year period. Compared to control group, patients presenting with stroke had higher plasma hsCRP level (3.3 ± 3.8 1.3 ± 2.2 mg/L, < 0.01). Furthermore, in the group of patients with stroke, the mean plasma hsCRP level was higher in patients who developed subsequent vascular diseases or died as compared with the patients without further complications (4.4 ± 4.3 2.7 ± 3.3 mg/L, < 0.01). Compared to the lowest tertile of hsCRP level, the relative risk for vascular events or death in stroke patients was 2.91 in the highest tertile of hsCRP (95% CI, 1.54–5.50, = 0.001). This increase in relative risk for vascular events or death in stroke patients continued after adjustment for age, sex and other cardiovascular risk factors such as hypertension and diabetes ( : 2.771, 95% CI: 1.367–5.617, = 0.005). These findings indicate that increased hsCRP level is associated with worsening prognosis after stroke in Chinese patients and suggests that inflammation is correlated with stroke outcome.

关键词： C-reactive protein inflammation stroke

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Risk factors of prognosis after acute kidney injury in hospitalized patients

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《医学前沿（英文）》 2017年第11卷第3期页码 393-402 doi: 10.1007/s11684-017-0532-9

摘要：

The risk factors, especially laboratory indicators, of prognosis after acute kidney injury (AKI) remain unclear. We conducted a retrospective survey of Chinese People’s Liberation Army General Hospital from January 1, 2012 to December 31, 2012 according to the AKI diagnosis standard issued by Kidney Disease Improving Global Outcomes. The epidemiological features and factors influencing hospital mortality and renal function recovery were evaluated through logistic regression analysis. Among 77 662 cases of hospitalized patients, 1387 suffered from AKI. The incidence rate and mortality of AKI were 1.79% and 14.56%, respectively. Multivariate logistic regression analysis revealed that high AKI stage, age greater than 80 years, neoplastic disease, low cardiac output, increased white blood cell count, and decreased platelet count and serum albumin levels were the risk factors affecting the mortality of AKI patients. Conversely, body mass index between 28 and 34.9 was a protective factor. Increased AKI stage, tumor disease, post-cardiopulmonary resuscitation, and RRT were the risk factors of renal function recovery upon discharge. In addition to traditional risk factors, white blood cell count, platelet count, albumin, and BMI were the predictors of the mortality of AKI patients. No laboratory indicators were found to be the risk factors of renal function recovery in AKI patients.

关键词： acute kidney injury risk factors prognosis

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Heterogeneity of the tumor immune microenvironment and clinical interventions

《医学前沿（英文）》 2023年第17卷第4期页码 617-648 doi: 10.1007/s11684-023-1015-9

摘要： Heterogeneity of the tumor immune microenvironment and clinical interventions

关键词： Heterogeneity tumor immune

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Proteins moonlighting in tumor metabolism and epigenetics

Lei Lv, Qunying Lei

《医学前沿（英文）》 2021年第15卷第3期页码 383-403 doi: 10.1007/s11684-020-0818-1

摘要： Cancer development is a complicated process controlled by the interplay of multiple signaling pathways and restrained by oxygen and nutrient accessibility in the tumor microenvironment. High plasticity in using diverse nutrients to adapt to metabolic stress is one of the hallmarks of cancer cells. To respond to nutrient stress and to meet the requirements for rapid cell proliferation, cancer cells reprogram metabolic pathways to take up more glucose and coordinate the production of energy and intermediates for biosynthesis. Such actions involve gene expression and activity regulation by the moonlighting function of oncoproteins and metabolic enzymes. The signal−moonlighting protein−metabolism axis facilitates the adaptation of tumor cells under varying environment conditions and can be therapeutically targeted for cancer treatment.

关键词： moonlighting function tumor metabolism epigenetics

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Complex interplay between tumor microenvironment and cancer therapy

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《医学前沿（英文）》 2018年第12卷第4期页码 426-439 doi: 10.1007/s11684-018-0663-7

摘要：

Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.

关键词： tumor microenvironment therapy response treatment resistance

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Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma

《医学前沿（英文）》 2023年第17卷第4期页码 699-713 doi: 10.1007/s11684-022-0972-8

摘要： Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%–50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

关键词： anti-CD19 chimeric antigen receptor T immunotherapy diffuse large B cell lymphoma tumor microenvironment tumor-associated macrophage metabolism

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Progress in tumor vascular normalization for anticancer therapy: challenges and perspectives

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《医学前沿（英文）》 2012年第6卷第1期页码 67-78 doi: 10.1007/s11684-012-0176-8

摘要：

Antitumor angiogenic therapy has been shown promising in the treatment of several advanced cancers since the approval of the first antiangiogenic drug Avastin in 2004. Although the current antiangiogenic drugs reduce the density of tumor blood vessels and result in tumor shrinkage at the early stage of treatment, recent studies have shown that antiangiogenic therapy has transient and insufficient efficacy, resulting in tumor recurrence in patients after several months of treatment. Blockage of blood and oxygen supplies creates a hypoxic and acidic microenvironment in the tumor tissues, which fosters tumor cells to become more aggressive and metastatic. In 2001, Jain proposed tumor vascular normalization as an alternative approach to treating cancers based on the pioneering work on tumor blood vessels by several other researchers. At present, normalizing the disorganized tumor vasculature, rather than disrupting or blocking them, has emerged as a new option for anticancer therapy. Preclinical and clinical data have shown that tumor vascular normalization using monoclonal antibodies, proteins, peptides, small molecules, and pericytes resulted in decreased tumor size and reduced metastasis. However, current tumor vascular normalizing drugs display moderate anticancer efficacy. Accumulated data have shown that a variety of vasculogenic/angiogenic tumor cells and genes play important roles in tumor neovascularization, growth, and metastasis. Therefore, multiple-targeting of vasculogenic tumor cells and genes may improve the efficacy of tumor vascular normalization. To this end, the combination of antiangiogenic drugs with tumor vascular normalizing therapeutics, as well as the integration of Western medicine with traditional Chinese medicine, may provide a good opportunity for discovering novel tumor vascular normalizing drugs for an effective anticancer therapy.

关键词： angiogenesis vasculogenesis neovascularization tumor vasculature normalization traditional Chinese medicine