DNA甲基化酶1在乙肝相关性肝癌中的表达及意义

目的:探讨DNA甲基化酶1(DNMT1)在乙肝相关性肝癌中表达的临床意义。方法:免疫组化检测66例乙肝相关性肝癌组织术后DNMT1表达,并对患者临床病理资料进行分析。结果:DNMT1在乙肝相关性肝癌组织中阳性率为40.9%,DNMT1高表达组与低表达组在性别、年龄及肿瘤大小方面无明显差异(P=0.900,P=0.509,P=0.347),在肿瘤结节、包膜及微血管浸润方面亦无明显差异(P=0.385,P=0.690,P=0.149),DNMT1高表达组与低表达组在Edmondson分级、BCLC分期及复发方面有明显差异(P=0.014,P=0.032,P=0.014)。结论:在乙肝相关性肝癌组织中存在DNMT1蛋白高表达,DNMT1高表达与患者恶性病理特征及复发具有一定作用,与患者具有较差的预后有关。     

P-selectin-mediated platelet adhesion promotes tumor growth

Blood platelets foster carcinogenesis. We found that platelets are accumulated in human tumors. P-selectin deficiency and soluble P-selectin abolish platelet deposition within tumors, decreasing secretion of vascular endothelial growth factor and angiogenesis, thereby suppressing tumor growth. Binding of the P-selectin cytoplasmic tail to talin1 triggers the talin1 N-terminal head to interact with the β3 cytoplasmic tail. This activates αIIbβ3 and recruits platelets into tumors. Platelet infiltration into solid tumors occurs through a P-selectin-dependent mechanism.     

Efficacy and safety analysis of trastuzumab and paclitaxel based regimen plus carboplatin or epirubicin as neoadjuvant therapy for clinical stage II-III,HER2-positive breast cancer patients: a phase 2, open-label,multicenter, randomized trial

This trial was designed to compare the efficacy and safety between epirubicin (E) and carboplatin (C) in combination with paclitaxel (P) and trastuzumab (H) in neoadjuvant setting. In 13 Chinese cancer centers, 100 patients with HER2-positive, locally advanced breast cancer were 1:1 randomized to receive medication as follows: trastuzumab and paclitaxel weekly combined with carboplatin weekly for PCH group, or epirubicin every 3 weeks for PEH group. Patients were given 4 to 6 cycles of chemotherapy. The primary endpoint was pathologic complete response (pCR) rate, which was no significant difference in PCH and PEH regimen (39.1% vs. 48.8%; p=0.365). However, PEH regimen achieved higher pCR in luminal-B (HER2-poitive) subgroup (55.0% vs. 24.0%; p = 0.033), but not in ERBB2+ subgroup (42.9% vs. 57.1%; p = 0.355). PEH regimen showed a favorable efficacy in PIK3CA mutated subgroup (69.2% vs.23.5%, p=0.012). No significant difference was observed in the subgroup analysis of TP53 mutation status, PTEN expression, FCGR2A SNP and FCGR3A SNP. Both regimens as neoadjuvant chemotherapy achieve similar efficacy and safety. PEH might improve pCR rate, especially in the luminal-B subtype and PIK3CA mutation subtype. PEH is feasible and less likely to increase the incidence of acute cardiac events compared to PCH.     

ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition

As the primary cause of lung cancer, tobacco smoke (TS) promotes the initiation and progression of lung tumorigenesis. Epithelial-mesenchymal transition (EMT) is a crucial process involved in cell malignant transformation. The role of ERK5, the lesser studied member of MAPKs family, in regulating TS-triggered pulmonary EMT has not been investigated. Normal human bronchial epithelial cells and BALB/c mice were used as in vitro and in vivo TS exposure models. Exposure of normal human bronchial epithelial cells to TS for 7 days induced morphological change, enhanced migratory and invasive capacities, reduced epithelial marker expression and increased mesenchymal marker expression. Importantly, we demonstrated for the first time that ERK5 negatively regulated TS-mediated lung epithelial EMT, as evidenced by the findings that TS suppressed ERK5 activation, and that TS-triggered EMT was mimicked with ERK5 inhibition and reversed by ERK5 overexpression. The negative regulation of ERK5 on pulmonary EMT was further confirmed in mice exposed to TS for 12 weeks. Taken together, our data suggest that ERK5 negatively regulates TS-mediated pulmonary EMT. These findings provide new insight into the molecular mechanisms of TS-associated lung tumorigenesis and may open up new avenues in the search for potential target of lung cancer intervention.     

Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma

Immune checkpoint signaling plays an important role in immunosuppression in multiple myeloma (MM). Blood levels of soluble programmed death-ligand 1 (sPD-L1), a checkpoint-relevant protein, might predict treatment response and survival outcomes in MM patients. We used an enzyme-linked immunosorbent assay to measure serum sPD-L1 levels in 81 newly diagnosed MM patients. We found that myeloma patients had higher sPD-L1 concentrations than healthy controls. The best sPD-L1 cutoff value for predicting disease progression risk was 2.783 ng/mL. The overall response rate to treatment was higher in low sPD-L1 patients than in high sPD-L1 patients. The 3-year progression free survival (PFS) and overall survival (OS) rates for all patients were 16% and 64%, respectively. Multivariate survival analysis including Eastern Cooperative Oncology Group performance status score, treatment response, and sPD-L1 level showed that a less than partial treatment response (PR) and higher sPD-L1 levels (>2.783 ng/ml) were independent prognostic factors for shorter PFS; neither factor was predictive of OS. The serum sPD-L1 level is a valuable biomarker for predicting treatment response and an independent prognostic factor for PFS. PD-1/PD-L1 blockade may be a promising novel immune-based therapeutic strategy in MM.     

18F-fluorodeoxyglucose (FDG) PET/CT after two cycles of neoadjuvant therapy may predict response in HER2-negative,but not in HER2-positive breast cancer

The aim of this prospective study was to assess the ability of 18F-fluorodeoxyglucose (¹⁸FDG) positron emission tomography/computed tomography (PET/CT) scanning to predict pathological complete response (pCR) in breast cancer, and to investigate whether timing of the scan and trastuzumab treatment influence the accuracy of pCR prediction in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. We treated 81 locally advanced breast cancer patients with four cycles of neoadjuvant chemotherapy (NAC). HER2-negative breast cancer patients received NAC alone, while HER2-positive breast cancer patients received NAC plus trastuzumab. ¹⁸FDG PET/CT scans were scheduled at baseline and after the second cycle of NAC. Axillary lymph node (ALN) dissection was performed after the last cycle of neoadjuvant therapy. Relative changes in standardized uptake values (SUV) between the two PET/CT scans (ΔSUV) in primary tumors and ALN metastases were calculated. There were 75 patients with 150 PET/CT scans in the final analysis, including 41 HER2-negative and 34 HER2-positive cases. In the HER2-negative group, the ΔSUV predicted overall and ALN pCR; the receiver operating characteristics-areas under curve (ROC-AUC) were 0.87 and 0.80 (P = 0.0014 and 0.031, respectively) and the negative predictive values were 94% and 89% respectively. However, in the HER2-positive group, ΔSUV could predict neither overall nor ALN pCR; the ROC-AUCs were only 0.56 and 0.53, with P = 0.53 and 0.84, respectively. Hence, the ΔSUV after two cycles of neoadjuvant therapy could predict pCR in HER2-negative patients treated with NAC alone, but not in HER2-positive patients treated with NAC plus trastuzumab.     

A network-based method to evaluate quality of reproducibility of differential expression in cancer genomics studies

BACKGROUND

Personalized cancer treatments depend on the determination of a patient''s genetic status according to known genetic profiles for which targeted treatments exist. Such genetic profiles must be scientifically validated before they is applied to general patient population. Reproducibility of findings that support such genetic profiles is a fundamental challenge in validation studies. The percentage of overlapping genes (POG) criterion and derivative methods produce unstable and misleading results. Furthermore, in a complex disease, comparisons between different tumor subtypes can produce high POG scores that do not capture the consistencies in the functions.

RESULTS

We focused on the quality rather than the quantity of the overlapping genes. We defined the rank value of each gene according to importance or quality by PageRank on basis of a particular topological structure. Then, we used the p-value of the rank-sum of the overlapping genes (PRSOG) to evaluate the quality of reproducibility. Though the POG scores were low in different studies of the same disease, the PRSOG was statistically significant, which suggests that sets of differentially expressed genes might be highly reproducible.

CONCLUSIONS

Evaluations of eight datasets from breast cancer, lung cancer and four other disorders indicate that quality-based PRSOG method performs better than a quantity-based method. Our analysis of the components of the sets of overlapping genes supports the utility of the PRSOG method.     

Association of five single nucleotide polymorphisms at 6q25.1 with breast cancer risk in northwestern China

CCDC170 and ESR1, located at 6q25.1, were associated with breast cancer (BC) risk by genome-wide association studies. Our goal was to validate the association between CCDC170-ESR1 polymorphisms and BC risk in the population of northwestern China. A case-control study of 551 patients with BC and 577 control individuals was conducted from January 2011 to November 2014. We analyzed five BC-associated single nucleotide polymorphisms (SNPs) identified in CCDC170-ESR1 by previous studies. Logistic regression models were used to derive odds ratios (ORs) and 95% confidence intervals after adjusting for body mass index and age. The minor alleles of rs3757318, rs3734805, and rs2046210 were associated with increased BC risk (OR = 1.30, p = 0.005; OR = 1.28, p = 0.006; OR = 1.20, p = 0.033, respectively) in an allelic model analysis. Those three SNPs had a coincident significant association with increased BC risk in genetic models and stratification analyses. A new haplotype, “CT”, was associated with a 1.31-fold increased risk of BC (OR = 1.31, p = 0.006). The “C” allele of rs9383951 was associated with a reduced risk of BC (OR = 0.69, p = 0.048) in estrogen receptor-positive individuals under the log-additive model. Our data provide new evidence of the association between CCDC170-ESR1 and BC susceptibility in the population of northwestern China.     

藏医真布病与中医痹症的对比探讨

中医学和藏医学同属于中国传统医学,拥有各自独特的文化背景及理论体系,二者对疾病的诊断、辨证、治疗手段都有各自的特点。藏医真布病（类似于现代医学中的类风湿性关节炎,属于中医痹症范畴）作为高原地区的常见病及多发病,具有较高的致残率。藏医学对真布病的认识不仅理论上有据可循,其疗效经过长期的临床验证,药物疗法与药浴等外治疗法结合更是具有毒副作用小、效果显著、安全经济等优点。本文以藏医和中医的理论背景为基础,通过藏医真布病、中医痹症在病因病机及治疗手段等方面的对比,讨论藏医药治疗真布病的优势与特点,提出对藏医未来发展思路的建议。