In the tumor microenvironment, tumor-associated macrophage, as polarized macrophages M2 phenotype, can promote tumor progression and affect the prognosis of cancer. Significant attention has been drawn towards tumor-associated macrophage in recent years. In this review, we describe the polarization state of macrophages determined by tumor microenvironment and the recruitment of tumor-associated macrophage. We also pay special attention to the interaction between tumor-associated macrophages and tumors, discuss and summarize various targeted therapy strategies for tumor-associated macrophages, aiming to provide a reference for the future development of these novel and effective anti-cancer treatments.
ObjectiveTo summarize the biological characteristics of human epidermal growth factor receptor 2 (HER-2/neu) gene, the expression and meaning of HER-2/neu gene in gastric cancer, and clinical application of targeted medicine of HER-2/neu gene in gastric cancer. MethodsRelated literatures about HER-2/neu gene and gastric cancer were retrieved for a review. ResultsHER-2/neu gene encoded human epidermal growth factor receptor, and it participated in the gene regulation of tumor cell proliferation, invasion, and metastasis through the downstream signal transduction pathway. Amplification of HER-2/neu gene or overexpression of HER-2 was closely bound up to the occurrence and development of gastric cancer, however, whether it could be used as independent prognostic factors of gastric cancer remained to be controversial. Several targeted medicine of HER-2/neu gene had applied to clinical at present, and all of them obtained good short-term effect. ConclusionHER-2/neu gene is a reliable target of gastric cancer and targeted medicine of HER-2/neu gene has a promising prospect.
High-grade gliomas are the most common malignant primary central nervous system tumors with poor prognosis. The operation based on the principle of maximum safe resection of tumors, combined with radiation therapy and chemotherapy, is the primary treatment method. This treatment only delays the progression of high-grade gliomas, and almost all patients eventually develop disease progression or relapse. With the development of molecular biology, immunology, and genomics, people have a deeper understanding of the pathogenesis of gliomas. Targeted therapy, immunotherapy, and other comprehensive treatments are expected to become potential treatments for high-grade gliomas. This article reviews the current status of medical treatment of primary and recurrent high-grade gliomas, and the research progress of high-grade gliomas in targeted therapy and immunotherapy.
ObjectiveTo reveal the true value of plasma detection of epidermal growth factor receptor (EGFR) mutation for early-stage non-small cell lung cancer (NSCLC) gene diagnosis and to predict survival prognosis. MethodsTissue samples of positive EGFR mutations by using amplification refractory mutation system (ARMS) method were surgically resected from 198 patients with stage I-IV NSCLC between February 2014 and June 2015 in Tangdu hospital. Paired blood samples were collected before surgery. And the cellfree DNA (cfDNA) in plasma was extracted, plasma EGFR mutations were detected by real-time polymerase chain reaction (PCR). Concentration of cfDNA was measured by ultraviolet spectrophotometry. Follow-up observation for stage ⅢA patients was put into force after surgery. Kaplan-Meire was used in survival analysis. ResultsThe sensitivity of EGFR mutation for the 198 paired tissues and plasma samples was 17.2%.The sensitivity was positively correlated with TNM stage and negatively correlated with tumor differentiation. The sensitivity of sage ⅢA was 33.3%, significantly higher than that of the patients at stage ⅠA (1.6%, P=0.000) and stage ⅠB (7.9%, P=0.004). The sensitivity of poor differentiation was 36.8%, significantly higher than that of high differentiation (0.0%, P=0.000) and moderate differentiation (15.7%, P=0.010). There was no correlation between plasma cfDNA concentration and patient characteristics. Survival analysis showed that plasma detection was a vital factor for predicting postoperative survival prognosis of stage ⅢA patients (P=0.014). ConclusionTissue samples cannot be replaced by plasma samples for epidermal growth factor receptor (EGFR) mutation test in early-stage NSCLC patients, currently. When the sensitivity increases dramatically in the plasma samples of stage ⅢA NSCLC and poor differentiation tumor, we recommend using plasma detection for gene diagnosis, dynamic monitoring of EGFR mutations in stage ⅢA or poorly differentiated tumors, especially in NSCLC patients whose tissue samples cannot be obtained by surgery. And plasma EGFR detection is a valuable method of forecasting survival prognosis for locally advanced NSCLC patients.
Objective To analyze the factors associated with the adoption of targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and to generate evidence to inform decision-making on public security policy regarding innovative anticancer medicines for the benefit of patients. Methods The study population comprised female patients diagnosed with HER2-positive breast cancer and treated at Fujian Cancer Hospital from 2014 to 2020. The patients were eligible for targeted therapy. The demographic and sociological characteristics and clinical information of patients were extracted from the hospital information system. We performed binary logistic regression analysis of factors associated with the adoption of targeted therapy in patients with HER2-positive breast cancer. We also divided the participants into two groups according to their tumor stage for subgroup analysis. Results A total of 1 041 female patients with HER2-positive breast cancer were included, among them, 803 received targeted therapy. In September 2017, molecular-targeted medicines for HER2-positive breast cancer began to be included in the local basic health insurance program. Only 282 (35.1%) patients adopted targeted therapy before September 2017, after which this number increased to 521 (64.9%). Among the patients who adopted targeted therapy, most were formally employed (45.8%) and enrollees of the urban employee health insurance program (66.0%). Among those who did not adopt targeted therapy, most were unemployed (42.4%) and enrollees of the resident health insurance program (50.0%). Binary logistic regression analysis revealed that patient occupation, gene expression of estrogen receptor, tumor stage, surgery or not, radiotherapy or not, and undergoing treatment before or after September 2017 were correlated with the adoption of targeted therapy (P<0.05). Conclusions Inclusion of targeted medicines for HER2-positive breast cancer in the health insurance program substantially increased the overall administration of these therapies. Individual affordability is a critical factor associated with the application of targeted therapy in eligible patients. Future policies should enhance the public security of patients with a relatively weak ability to pay and provide insurance coverage for innovative anti-cancer medicines.
Objective To summarize the development of gallbladder carcinoma related resistance genes and targeted therapy. Methods Domestic and international publications online involving resistance genes and targeted therapy of gallbladder carcinoma in recent years were collected and reviewed. Results Recent studies had shown that chemotherapy drug resistance of gallbladder carcinoma mainly involved lysosome protein transmembrane β4 （LAPTM4B） gene， NF-E2-related factor 2 （Nrf2） gene， and cancer stem cells （CSCs）. While the latest gene targets of treatment for gallbladder carcinoma mainly involved LAPTM4B， Nemo-like kinase （NLK）， tissue factor way inhibitor-2 （TFPI-2）， vascular endothelial growth factor-D （VEGF-D）， epidermal growth factor receptor （EGFR）， and melanoma differentiation-associated gene 7/interleukin 24 （mda-7/IL-24） gene. Conclusion The research involving resistance genes and targeted therapy of gallbladder carcinoma has make a certain progress， which broaden the concept of traditional treatment of gallbladder carcinoma.
Graves’ ophthalmopathy (GO) is an autoimmune disease, and there is no specific treatment drug. Glucocorticoid (GC) therapy is still the first-line therapy for patients with moderate to severe GO. Targeted therapy may become a novel treatment due to GC’s adverse drug reactions. As the in-depth study of the pathogenesis of GO, many targeted drugs with randomized clinical trial (RCT) treatment have appeared in recent years, such as anti-insulin growth factor 1 receptor (teprotumumab), anti-CD20 (rituximab) and anti-interleukin(IL)-6 receptor (tocilizumab). It is worth noting that teprotumumab has been approved by US Food and Drug Administration in recently, and may quickly become the first-line therapy for GO. The anti-B cell stimulating factor (belimumab) which is undergoing RCT is waiting for the result of RCT to reveal. Anti-tumor necrosis factor-α (such as etanercept, adalimumab, and infliximab) which only used in case reports requires RCT further verification. In addition, anti-IL-17/IL-23, thyroid stimulating hormone receptor, CD40 targets and target therapies may have potential clinical value for GO due to the successful use of these target therapies in vitro experiments and other autoimmune diseases. This paper focus on the progress of targeted therapy of GO in China and abroad in recent years.
Metastatic renal cell carcinoma accounts for 20%-30% of newly diagnosed renal cell carcinoma and its prognosis is poor. It is not sensitive to radiotherapy or chemotherapy, and traditional cytokine therapy has limited efficacy in patient with metastatic renal cell carcinoma. In recent years, with the emergence of targeted drugs and immune checkpoint inhibitors, the survival of patients with metastatic renal cancer has been greatly improved. This article reviews treatment and research progress of metastatic renal cell carcinoma. It mainly introduces the medical treatment, including cytokine therapy, targeted therapy and emerging immunotherapy, and further analyzes the value of cytoreductive nephrectomy in the context of targeted therapy. The purpose of this article is to provide evidence for reasonable choices of treatment regimens in order to better guide clinical treatment.
Objective To analyze the clinical features and survival of lung cancer with pleural effusions. Methods A total of 982 consecutive patients with a newly diagnosed lung cancer from January 2008 to December 2014 were retrospectively reviewed. To analyze the clinical features and survival differences, the total patients were divided into the following two groups: with (n=204) or without (n=778) pleural effusions. Results Lung cancer comprised 682 (69.5%) males and 300 (30.5%) females, with an average age of 59.74 years (19–93 years). There were 487(49.6%) squamous carcinoma, 254 (25.9%) adenocarcinoma and 166 (16.9%) small cell lung cancer; 113 (11.5%) lung cancer at early stage (Ⅰ–Ⅱ), 247 (25.2%) cases at stage Ⅲ and 567 (57.7%) at stage Ⅳ. The median survival time of all patients was 12 months. Patients with pleural effusions had a worse prognosis compared to patients without (median survival time: 11 vs.12 months, P=0.003), the median survival time could be reduced by 1 month in males (P=0.004), 3 months in elder patients over 60 years (P<0.001), 4 to 8 months in carcinoma and small cell lung cancer (P≤0.001), and 2 to 3 months in advanced lung cancer (stage Ⅲ and Ⅳ) (P<0.05). Any or combined treatment of surgery, radiotherapy, chemotherapy and targeted therapy was associated with an improved overall survival of about 2 months (P=0.009), and targeted therapy could even improve the median survival time by 1 to 8 months (P=0.002). Conclusions About 20.8% of the patients developed pleural effusion at the same time during the course of lung cancer. Pleural effusion is a poor prognostic factor of lung cancer.
Objective To systematically evaluate the safety and efficacy of trastuzumab combined with chemotherapy for HER-2 positive patients with advanced gastric cancer. Methods We searched ClinicalTrails.gov, PubMed, EMbase, Web of Science, The Cochrane Library (Issue 5, 2016), CNKI, CBM, WanFang Data, VIP and major meeting proceeding databases (ASCO and ESMO) from inception to May 2016, to collect randomized controlled trials (RCTs) or non-RCTs about trastuzumab combined with chemotherapy versus chemotherapy alone for advanced gastric cancer. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was performed by using RevMan 5.3 software. Results Nine studies involving 1 034 HER-2 positive patients were included, of which three were RCTs and the other six were non-RCTs. Meta-analysis results indicated that the trastuzumab combined with chemotherapy group (the trial group) was superior to the chemotherapy alone group (the control group) in complete remission (OR=2.76, 95%CI 1.40 to 5.44,P=0.003), partial remission (OR=1.81, 95%CI 1.40 to 2.33,P<0.000 01), overall response rate (OR=2.09, 95%CI 1.63 to 2.68,P<0.000 01) and disease control rate (OR=2.20, 95%CI 1.63 to 2.98,P<0.000 1), while there was no statistical significances in stable disease (OR=0.87, 95%CI 0.66 to 1.14,P=0.31). In terms of safety, the incidence of diarrhea (OR=1.51, 95%CI 1.10 to 2.06,P=0.01) and erythra (OR=4.35, 95%CI 1.25 to 15.10,P=0.02) in the trial group were higher than the control group. However, other adverse reactions were no significant differences in two groups. Conclusion Compared with chemotherapy alone, trastuzumab combined with chemotherapy in the treatment of HER-2 positive patients with advanced gastric cancer can significantly improve response rate, but it may increase the incidence of diarrhea and erythra. Because of the limited quality and quantity of the included studies, the above conclusion needs to be verified by conducting more high quality studies.