摘要:Pancreatic cancer is one of the more dismal gastrointestinal tumors due to the obscure symptoms in the early stage of disease, rapid progression and insensitivity to chemotherapy. The 5-year survival rate is only approximately 9% for patients with pancreatic cancer. In the recent years, with the change in dietary structure and life style as well as the improvement of clinical detection rate, the incidence of pancreatic cancer is increasing annually, and it severely undermines the health of people. However, the advance in molecular biology provides more potential targets for the treatment of pancreatic cancer. Besides, well-conducted clinical trials continue to translate more theoretical innovations from bench to bedside. These both can improve the prognosis of pancreatic cancer eventually. The present review summarized the important findings in pancreatic cancer research in 2020.
关键词:Pancreatic cancer;Basic research;Clinical research
摘要:Background and purpose: Metastasis remains the cause of 90% of death from cancer. By analyzing the distribution of metastatic sites and survival status of 20 000 metastatic cancer patients from a hospital-based cancer registry database, this study provides the real-world data for the cancer treatment and survival management in China. Methods: A total of 20 067 cancer patients who were diagnosed as having metastatic caner or developed metastasis during the follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were included in this study. Medical records review, telephone visits and death registry data linkage were applied in collecting endpoint data. The first follow-up date was the diagnosis date of metastasis, and the last follow-up date was November 1, 2020. Kaplan-Meier method was applied in evaluating the 1-, 3- and 5-year overall survival (OS) rates for overall cancer and site-specific cancer patients. Results: The median follow-up time was 46.7 months, 13 170 cases died during the follow- up, 60.05% was single-site metastasis, and 39.95% was multiple-site metastasis. Among all metastable sites, the proportion of metastasis to liver was 33.82%, 26.25% to lung, 26.22% to bone, and 9.22% to brain. The incidence of brain metastasis was the highest in lung cancer patients among all cancer types (31.14%). Liver was the most frequent metastatic site in pancreatic cancer (77.85%), and bone was the most frequent metastatic site in patients with prostate cancer (83.20%). Subgroup analysis showed that liver metastasis was easier to be observed in males than in females (35.46% vs 31.89%, P<0.001), whereas lung, bone and brain metastases were more frequently to be observed in females (24.96% vs 27.76%, 25.26% vs 27.34%, 8.34% vs 10.25, P<0.001). After metastasis, the 1-, 3- and 5-year OS rates of overall cancer were 65.59% (95% CI: 64.90-66.27), 33.42% (95% CI: 32.69-34.16) and 21.12% (95% CI: 20.39-21.84), respectively. Conclusion: The metastasis patterns for different cancer sites are different, and there is sex heterogeneity. Currently, the survival rate after metastasis is poor, and the future research combining with treatment strategies is required to improve the survival of advanced-stage cancer patients.
摘要:Background and purpose: Solute carrier family 6 member 3 (SLC6A3) is highly expressed in patients with renal clear cell carcinoma. However, the effect of SLC6A3 on the metastasis of renal clear cell carcinoma and its molecular mechanism are still unclear. This study aimed to investigate the effect of SLC6A3 on proliferation and migration of renal clear cell carcinoma cells and its potential molecular mechanism. Methods: The expression of SLC6A3 in renal clear cell carcinoma and adjacent tissues collected in Shaanxi Cancer Hospital from January 2017 to January 2018 was detected by immunohistochemistry. The expression of SLC6A3 in renal clear cell carcinoma cell line SNU-349 was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. ShNC and shSLC6A3 plasmids were constructed and transfected into SNU-349 cells. Changes in cell proliferation, apoptosis and invasion ability of SLC6A3 downregulated cells were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and transwell assay. The effects of SLC6A3 downregulation on phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) signaling pathway were analyzed by Western blot. Results: SLC6A3 was highly expressed in renal clear cell carcinoma tissues and cells (P<0.05). After SLC6A3 was downregulated, cell proliferation and invasion ability were significantly decreased (P<0.05), apoptotic rate was significantly increased (P<0.05), and cell cycle S-phase arrest was observed (P<0.05). The expression levels of PI3K and phosphorylation levels of Akt in cells were significantly reduced after SLC6A3 was downregulated (P<0.05). Conclusion: SLC6A3 is highly expressed in renal clear cell carcinoma tissues. Downregulation of SLC6A3 inhibits cell proliferation and invasion, and promotes cell apoptosis. SLC6A3 may affect the growth of SNU-349 cells by regulating the PI3K/Akt signaling pathway.
关键词:Renal clear cell carcinoma;Solute carrier family 6 member 3;Proliferation;Migration
摘要:Background and purpose: As the targeted antibody of human epidermal growth factor receptor 2 (HER2), trastuzumab resistance gets more and more attention. This study aimed to explore the role of miR-375 in the occurrence of trastuzumab resistance in breast cancer cells through regulating epithelial-mesenchymal transition (EMT) by targeting Yes-associated protein 1 (YAP1). Methods: Trastuzumab-resistant breast cancer cell line was established. miR-375 mimic and recombinant plasmid YAP1 were transfected into SK-BR-3R cells. The sensitivities of each breast cancer cell line to trastuzumab were detected by MTT assay, and proliferation was detected by colony formation assay. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were applied to detect mRNA and protein expressions of miR-375, vimentin, E-cadherin and YAP1. Dual-luciferase reporter gene assay was conducted to verify the role of miR-375 in regulation of YAP1 transcription. A total of 25 breast cancer tissues from patients were collected to detect correlation in clinical performance. Results: Compared with NC group, after transfection with miR-375 mimic, the sensitivity to trastuzumab (P<0.01) and capacity of colony formation (P<0.01) for SK- BR-3R (resistance) cell line were decreased significantly, and the expression of vimentin was significantly downregulated, whereas E-cadherin was significantly upregulated (all P<0.05). YAP1 as downstream target gene of miR-375 was observed (P<0.01). MiR- 375 was negatively correlated with YAP1 in breast cancer tissues (r=-0.586 8, P=0.002 8). After miR-375 mimic and YAP1-MUT co- transfection in SK-BR-3R, compared with the control, the sensitivity to trastuzumab (P<0.01), capacity of colony formation (P<0.05) and the expressions of vimentin and E-cadherin were restored (P<0.05). Conclusion: miR-375 takes part in trastuzumab resistance of breast cancer cells through regulating EMT, which is mediated by targeting YAP1.
关键词:miR-375;Trastuzumab resistance;Breast cancer;Yes-associated protein 1;Epithelial-mesenchymal transition
摘要:Background and purpose: miR-122 is abnormally expressed in various tumors and involved in tumor cell proliferation and apoptosis, while cAMP response element-binding protein 1 (CREB1) is involved in esophageal cancer development. This study aimed to investigate the effect of miR-122-5p on proliferation of esophageal cancer cells and xenografts by targeting CREB1 and its mechanism. Methods: Forty-three specimens of esophageal cancer and corresponding adjacent normal tissues (3-5 cm from the edge of cancer) were collected after tumor resection in Quanzhou First Hospital Affiliated to Fujian Medical University from November 2017 to November 2019. The expressions of miR-122-5p mRNA and CREB1 mRNA in esophageal cancer tissues and cells were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Cells were divided into control group, miR-NC group, pc-NC group, miR-122-5p mimic group, pc-CREB1 group and miR-122-5p mimic+pc-CREB1 group. The miR-NC, pc-NC, miR-122-5p mimic and pc-CREB1 plasmids were transfected into EC109 cells separately or jointly using Lipofectamine TM 2000. The targeting relationship was verified by the dual-luciferase reporter assay. The cell proliferation was detected by MTT assay. Cell growth ability was tested by cloning formation experiment. The rate of apoptosis was detected by flow cytometry. The Ki-67 labelling index, proliferating cell nuclear antigen (PCNA), activated caspase-3, Bax, Bcl-2 and CREB1 were detected by Western blot. All nude mice were divided into four groups: control group, miR-122-5p mimic group, pc-CREB1 group, miR-122-5p mimic+pc-CREB1 group. Transfected EC109 cells were injected subcutaneously in the left armpit of nude mice. After 30 days, the nude mice were sacrificed, the subcutaneous tumors were completely removed, and the volume and weight of the transplanted tumors were measured. The Ki-67 labelling index and caspase-3 were detected by immunohistochemistry. Results: miR-122-5p was expressed at a low level in esophageal cancer tissues and cells, while CREB1 was highly expressed in esophageal cancer tissues and cells (both P<0.01). miR-122-5p targeted down-regulation of CREB1 was observed. Compared with the control group, the number of esophageal cancer cell clones in the miR-122-5p group decreased, PCNA and Ki-67 labelling index were down- regulated, the apoptotic rate increased, activated caspase-3 and Bax protein expressions were up-regulated, Bcl-2 protein expression was down-regulated, the volume and weight of esophageal cancer EC109 transplanted tumor decreased, the ratio of Ki-67 positive cells increased, and the ratio of caspase-3 positive cells decreased (all P<0.01). Overexpression of CREB1 reversed the effects of miR-122-5p on proliferation and apoptosis of esophageal cancer cells and transplanted tumors. Conclusion: miR-122-5p can inhibit the proliferation of esophageal cancer cells and induce apoptosis by targeted down-regulation of CREB1, thereby inhibiting the growth of esophageal cancer cells and transplanted tumors.
关键词:miR-122-5p;cAMP response element-binding protein 1;Esophageal cancer;Proliferation;Apoptosis
摘要:Background and purpose: Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer, and is prone to distant metastasis. The site of metastasis and tumor burden can predict the prognosis. The purpose of this study was to compare impacts of the different sites of distant metastasis and the number of metastatic organs on the prognosis of extensive- stage SCLC patients to provide reference for clinical decision. Methods: Clinical data of extensive-stage SCLC patients from May 2014 to February 2019 in Shanghai Pulmonary Hospital, Tongji University were collected, and the relationship between the sites of distant metastasis / the number of metastatic organs and overall survival (OS)/therapeutic efficacy was retrospectively analyzed. Results: Most of patients (69.0%) had distant metastasis at the initial diagnosis. The greater the number of metastatic organs, the shorter the median OS (P=0.007 9) and progression-free survival (PFS) (P=0.027 0). The median OS of patients with brain metastasis, bone metastasis, contralateral lung metastasis, liver metastasis and other organ metastasis were 14.83, 11.70, 14.47, 11.10 and 12.47 months, respectively (P=0.031 1). The median PFS of patients with brain metastasis, bone metastasis, contralateral lung metastasis, liver metastasis and other organ metastasis were 5.07, 4.07, 7.10, 3.87 and 4.80 months, respectively (P=0.033 6). Conclusion: Distant metastasis in patients with extensive-stage SCLC suggests poor prognosis, and the more metastatic organs, the worse the OS and PFS. Patient with liver and bone metastases has worse OS and PFS suggesting poor prognosis.
关键词:Extensive-stage small cell lung cancer;Organ metastasis;Survival time
摘要:Background and purpose: There are various chemotherapy regimens for breast cancer, and multiple chemotherapy drugs are often used in combination. The chemotherapy cycle is long, and chemotherapy drugs cause many adverse reactions. In clinical diagnosis and treatment of tumor patients, liver injury caused by chemotherapy is also a common adverse reaction. Of the drug-induced liver injuries, liver injury caused by antitumor drugs accounts for 15%. We aimed to provide clinical strategies for chemotherapy patients to reduce adverse reactions, increase chemotherapy compliance and improve the quality of life of patients. Methods: We retrospectively analyzed the risk factors of liver injury caused by chemotherapy in patients with breast cancer who were treated in Fudan University Shanghai Cancer Center from January 2017 to December 2017. We enrolled breast cancer patients from Fudan University Shanghai Cancer Center and collected basic information including patient’s information, medical history, chemotherapy, and laboratory indicators related to liver function. According to the presence or absence of liver injury, the patients were divided into case group and control group. Univariate analysis of each factor level and multivariate analysis were used to explore the risk factors of liver injury caused by chemotherapy in patients with breast cancer. The prediction model of liver injury was established by binary logistic analysis, and the predictive ability of the model was tested by receiver operating characteristic (ROC) curve analysis. Results: A total of 724 patients with breast cancer in Fudan University Shanghai Cancer Center were eligible for inclusion in this study. The proportion of patients with liver injury during chemotherapy was 40.74%. The results of logistics analysis based on the results of univariate analysis showed that age, TNM stage, intensive chemotherapy regimen, paclitaxel combined with platinum chemotherapy regimen, anthracycline chemotherapy regimen and chemotherapy cycle became the independent risk factors for liver injury caused by chemotherapy in patients. The accuracy of the binary logistic model: P=1/1+Exp∑(0.901- AX 1 +1.01X 2 +TX 3 -1.82X 4 +5.225X 5 +1.256X 6 + 0.874X 7 -0.764X 8 ), with a specificity of 91.61% and a sensitivity of 81.69%, was 87.60%. The negative predictive value (NPV) was 87.92%, and the positive predictive value (PPV) was 87.00%. At the same time, ROC curve analysis showed that the area under the ROC curve was 0.923 (95% CI: 0.901-0.944, P<0.001). Conclusion: It is necessary to establish an effective prediction model to take certain intervention measures for patients with high-risk liver injury. The binary logistic prediction model established in this study has high accuracy, sensitivity and specificity, and can satisfy the prediction requirements of chemotherapy-induced liver injury in breast cancer patients. It lays the theoretical foundation for the prediction and clinical intervention of adverse reactions in breast cancer patients with liver injury at later stage.
摘要:Background and purpose: Neutrophil to lymphocyte ratio (NLR) is a simple, objective and inexpensive laboratory indicator, and its predictive value has been verified in different types of cancer. The purpose of this study was to integrate pretreatment indicators including clinical factors with NLR to predict axillary pathological complete response (apCR) after neoadjuvant therapy (NAT). Methods: From April 2016 to April 2020, 416 breast cancer patients with clinical nodal positive disease undergoing operation after NAT were included. The pretreatment clinicopathological factors and laboratory indexes were collected. The optimal cut-off values of age and laboratory indexes were determined by Youden index using receiver operating characteristic (ROC) curve analyses. The logistic regression analysis was applied to examine predictive factors of apCR. Then, a logistic model was developed according to multivariate analysis results, and it was analyzed using ROC curve and area under curve (AUC) value. Results: Among 416 patients, 37.3% (155) of them achieved apCR. The multivariate analysis showed that age (OR=0.528, 95% CI: 0.343-0.814), pathological grade (OR=1.846, 95% CI: 1.187-2.872), molecular subtype (OR=2.791, 95% CI: 1.780-4.377) and NLR (OR=0.302, 95% CI: 0.105-0.867) were indicated as independent predictors of apCR. Based on these factors, we built the logistic model to predict apCR: logit(P)=0.613×pathological grading+1.027×molecular subtype-0.638×age-1.196×NLR-0.244 (model checking χ 2 =54.478, P< 0.001). The AUC value of the logistic model was 0.702. Conclusion: Except for traditional clinical factors, the NLR level could also be identified as predictive factor of apCR after NAT. Integrating traditional clinical factors with NLR level could help to predict apCR and guide individualized treatment options.
关键词:Breast cancer;Neoadjuvant therapy;Neutrophil to lymphocyte ratio;Axillary lymph node;Pathological complete response
摘要:The application of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) has significantly improved the survival of patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, there are still a portion of patients with poor efficacy and prognosis. Therefore, it is urgently needed to find effective emerging prognostic markers. In the past few years, tumor mutational burden (TMB) was mainly used to screen patients who benefitted from immunotherapy and predict the efficacy. Recently, there are also corresponding exploratory studies on EGFR-mutant NSCLC. In this review, we summarized the challenges of TMB test and latest clinical research in EGFR-mutant advanced NSCLC.
摘要:Recent study has found that lipid metabolism has close relation to the occurrence, development and therapy of lung cancer and gradually becomes a hot topic in cancer cell metabolism. Analyzing the relationship between lipid metabolism and lung cancer may be helpful for accurate diagnosis, prediction of therapeutic efficacy and estimation of prognosis. Additionally, it is possible to develop drugs for tumor lipid metabolism. Therefore, this paper reviewed the characteristics of blood lipid in patients with lung cancer, their relationship to therapeutic efficacy and the medicines for lipid metabolism. This can provide reference for treatment targeting lipid metabolism in lung cancer.