No abstract

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases. Electronic supplementary material The online version of this article (10.1186/s13045-019-0702-0) contains supplementary material, which is available to authorized users.

Mitophagy, a process that selectively removes damaged organelles by autolysosomal degradation, is an early cellular response to ischemia. Mitophagy is activated in both cardiomyocytes and platelets during ischemia/reperfusion (I/R) and heart disease conditions. We focus on the molecular regulation of mitophagy and highlight the role of mitophagy in cardioprotection.

HuR is an ubiquitously expressed RNA-binding protein that stabilizes messenger RNA and regulates translation. This protein has been shown to play an important role in carcinogenesis and cancer progression. P-glycoprotein (P-gp) is the product of the multidrug resistance 1 gene, and the overexpression of P-gp induces multidrug resistance and represents a major obstacle in cancer chemotherapy. The purpose of this study was to determine the expression of HuR and P-gp in human breast cancer tissues and analyze the relationship between HuR or P-gp expression and the clinical-pathological variables and patient outcomes. Immunohistochemistry was used to determine HuR and P-gp expression in 82 human breast cancer tissues and 20 matched adjacent noncancerous tissues. Additionally, 16 benign breast tumor samples were used as controls. The overexpression of cytoplasmic HuR was found in breast cancer but not in the matched adjacent noncancerous tissues or benign breast tumors. The expression levels of cytoplasmic HuR were significantly associated with increased age, high nuclear grade, and the positive expression of the ER, PR, and HER-2/neu. HuR was also associated with the expression of P-gp protein. Furthermore, univariate analysis indicates that patients with high expression levels of cytoplasmic HuR or P-gp had significantly reduced survival compared to patients with low expression levels. A multivariate analysis showed that age at diagnosis, nuclear grade, and cytoplasmic HuR positivity were independent indicators for disease-free survival and overall survival in patients with breast cancer. In conclusion, cytoplasmic HuR expression detected by immunohistochemical staining is a negative prognostic indicator for survival in patients with breast cancer.

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Summary Mesenchymal stem cells (MSCs) are potential sources of cells for tissue repairing. However, little information is available regarding the therapeutic potency of intravenously transplanted MSCs for myocardial ischemia (MI). In the present study, MSCs were isolated from bone marrow of male rats and expanded in vitro. Three hours after ligation of left anterior descending artery, the transplanted group received an infusion of MSCs through the tail vein. At the same time, a coronary‐ligated control group was injected with culture medium. Homing of MSCs to the heart was assessed by expression of the Y chromosome sry gene using fluorescent in situ hybridization (FISH). At 1 week or 8 weeks after transplantation, sry positive cells were present in cardiac tissue in the transplanted group, but not in the hearts of control group. Cardiomyocytes, smooth muscle cells, and endothelial cells that bore sry gene were identified in transplanted group at 8 weeks after transplantation. Ultrastructural observation revealed that a large number of capillary and some immature myocytes were found to survive in the ischemia region. MSCs transplantation also decreased LVEDP pressure and −dP/dt, but increased LVSP and +dP/dt. The cardiac infarct size was significantly smaller in transplanted group than in control group. Our data suggest that intravenously transplanted MSCs improve cardiac performance and promote the regeneration of blood vessels and cardiomyocytes.

It remains controversial whether radical radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) still requires elective nodal irradiation (ENI), or only involved-field irradiation (IFI). In this study, a meta-analysis was conducted to compare ENI and IFI in the treatment of ESCC, in order to provide guidance for clinical practice. Literature on the use of ENI and IFI in the treatment of ESCC was retrieved, and the last access date was 31 December 2017. A meta-analysis was performed to evaluate the relative advantages and disadvantages of using ENI and IFI. Ten studies, involving a total of 1348 patients, were included in this analysis; of these, 605 patients underwent radiotherapy only, and 743 underwent radiochemotherapy. There was no significant difference in the 1-, 2- or 3-year local control rates between ENI and IFI, or in the 1-, 2- or 3-year overall survival rates. However, the incidences of ≥Grade 3 acute esophagitis and pneumonia were significantly lower in the IFI group. There were no differences in the rates of ≥Grade 3 myelosuppression or of out-field recurrence or metastasis between these two groups. Thus, neither local control rates nor overall survival rates differed significantly between the ENI and IFI groups, but in the latter group, incidences of severe radiation esophagitis and pneumonia were significantly lower. IFI was not associated with an increase in out-field recurrence or metastasis.

BackgroundResistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines.ResultsTwo human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing concentrations of docetaxel. Whole exome sequencing performed at five successive stages during this process was used to identify single point mutational events, insertions/deletions and copy number alterations associated with the acquisition of docetaxel resistance. Acquired coding variation undergoing positive selection and harboring characteristics likely to be functional were further prioritized using network-based approaches.A number of genomic changes were found to be undergoing evolutionary selection, some of which were likely to be functional. Of the five stages of progression toward resistance, most resistance relevant genomic variation appeared to arise midway towards fully resistant cells corresponding to passage 31 (5 nM docetaxel) for MDA-MB-231 and passage 16 (1.2 nM docetaxel) for MCF-7, and where the cells also exhibited a period of reduced growth rate or arrest, respectively. MCF-7 cell acquired several copy number gains on chromosome 7, including ABC transporter genes, including ABCB1 and ABCB4, as well as DMTF1, CLDN12, CROT, and SRI. For MDA-MB-231 numerous copy number losses on chromosome X involving more than 30 genes was observed. Of these genes, CASK, POLA1, PRDX4, MED14 and PIGA were highly prioritized by the applied network-based gene ranking approach. At higher docetaxel concentration MCF-7 subclones exhibited a copy number loss in E2F4, and the gene encoding this important transcription factor was down-regulated in MCF-7 resistant cells.ConclusionsOur study of the evolution of acquired docetaxel resistance identified several genomic changes that might explain development of docetaxel resistance. Interestingly, the most relevant resistance-associated changes appeared to originate midway through the evolution towards fully resistant cell lines. Our data suggest that no single genomic event sufficiently predicts resistance to docetaxel, but require genomic alterations affecting multiple pathways that in concert establish the final resistance stage.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2749-4) contains supplementary material, which is available to authorized users.