Long-term survivors of early breast cancer treated with chemotherapy are characterized by a pro-inflammatory biomarker profile compared to matched controls.


  • 影响因子:7.31
  • DOI:10.1002/ejhf.1758
  • 作者列表:"Tromp J","Boerman LM","Sama IE","Maass SWMC","Maduro JH","Hummel YM","Berger MY","de Bock GH","Gietema JA","Berendsen AJ","van der Meer P
  • 发表时间:2020-02-20

BACKGROUND:Chemo- and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment. The pathophysiology behind these late cardiac effects is poorly understood. Therefore, we studied a large panel of biomarkers from different pathophysiological domains in long-term BC survivors, and compared these to matched controls. METHODS AND RESULTS:In total 91 biomarkers were measured in 688 subjects: 342 BC survivors stratified either to treatment with chemotherapy ± radiotherapy (n = 170) or radiotherapy alone (n = 172) and matched controls. Mean age was 59 ± 9 years and 65 ± 8 years for women treated with chemotherapy ± radiotherapy and radiotherapy alone, respectively, with a mean time since treatment of 11 ± 5.5 years. No biomarkers were differentially expressed in survivors treated with radiotherapy alone vs. controls (P for all >0.1). In sharp contrast, a total of 19 biomarkers were elevated, relative to controls, in BC survivors treated with chemotherapy ± radiotherapy after correction for multiple comparisons (P <0.05 for all). Network analysis revealed upregulation of pathways relating to collagen degradation and activation of matrix metalloproteinases. Furthermore, several inflammatory biomarkers including growth differentiation factor 15, monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 16, tumour necrosis factor super family member 13b and proprotein convertase subtilisin/kexin type 9, elevated in survivors treated with chemotherapy, showed an independent association with lower left ventricular ejection fraction. CONCLUSION:Breast cancer survivors treated with chemotherapy ± radiotherapy show a distinct biomarker profile associated with mild cardiac dysfunction even 10 years after treatment. These results suggest that an ongoing pro-inflammatory state and activation of matrix metalloproteinases following initial treatment with chemotherapy might play a role in the observed cardiac dysfunction in late BC survivors.


背景: 乳腺癌的化疗和放疗 (BC) 可导致心脏毒性,甚至在初始治疗后数年。这些晚期心脏效应背后的病理生理学还知之甚少。因此,我们在长期 BC 幸存者中研究了一组来自不同病理生理结构域的大型生物标志物,并将其与匹配的对照进行了比较。 方法和结果: 在 688 名受试者中总共测量了 91 个生物标志物: 342 例 bc 幸存者,分为化疗 + 放疗 (n = 170) 或单纯放疗 (n = 172) 和匹配的控件。接受化疗 + 放疗和单纯放疗的女性平均年龄分别为 59 ± 9 岁和 65 ± 8 岁, 自治疗以来的平均时间为 11 ± 5.5 年。在接受单纯放疗治疗的幸存者与对照组中没有生物标志物的差异表达 (P 均&gt; 0.1)。与此形成鲜明对比的是,经过多重比较校正后,接受化疗 ± 放疗的 BC 幸存者中,相对于对照组,总共有 19 个生物标志物升高 (P



作者列表:["Abrahamsson H","Jensen BV","Berven LL","Nielsen DL","Šaltytė Benth J","Johansen JS","Larsen FO","Johansen JS","Ree AH"]

METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.

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作者列表:["Suvina V","Kokulnathan T","Wang TJ","Balakrishna RG"]

METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.

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来源期刊:Cancer letters
作者列表:["Zhou Z","Zhou Q","Wu X","Xu S","Hu X","Tao X","Li B","Peng J","Li D","Shen L","Cao Y","Yang L"]

METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.

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