We analyzed the number of circulating tumor cells (CTCs) and Epstein–Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The ...levels of CTCs and EBV DNA were measured at baseline and after first‐line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non‐mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first‐line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first‐line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first‐line chemotherapy was associated with significantly longer progression‐free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first‐line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first‐line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
What's new?
Endemic nasopharyngeal carcinoma (NPC) is associated with latent infection of the oncogenic Epstein‐Barr virus (EBV) and frequently metastasizes to distant lymph nodes and organs. Metastatic NPC is treated by serial administration of cytotoxic or targeted therapies and treatment response is generally assessed with serial imaging, which often fails to detect changes in tumor burden. Here, the authors show that the number of circulating tumor cells (CTCs) and EBV DNA levels before, after, and during first‐line chemotherapy are strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
Warming temperatures caused by climate change are predicted to vary temporally and spatially. For mid‐ and high‐latitude reptiles, the seasonal variation in warming temperatures experienced by ...embryos and hatchlings may determine offspring fitness, yet this has remained largely unexplored.
To evaluate the independent and interactive influence of seasonal variation in warming temperatures on embryonic and hatchling development, we incubated eggs and reared hatchlings of a cold‐climate oviparous ectothermic species, the Heilongjiang grass lizard (Takydromus amurensis), following a 2 × 2 factorial design (present climate versus warming climate for embryos × present climate versus warming climate for hatchlings). We then evaluated embryonic and hatchling development, including hatching success, incubation period, initial hatchling body size, hatchling metabolic rate, growth rate and survival in the mesocosms.
We found that warming temperatures shortened the incubation period and produced hatchlings with higher survival rates than those incubated under the present climate conditions. Similarly, hatchlings reared under a warming climate had similar growth rates and resting metabolic rates, but higher survival rates than those reared under the present climate. Hatchlings that experienced both warming incubation and warming growth conditions had the highest survival rates.
This study revealed that moderate warming temperatures (Representative Concentration Pathway, RCP 4.5, 1.1–2.6°C) experienced by embryos and hatchlings interact to benefit hatchling fitness in cold‐climate oviparous ectotherms. Our study also highlighted the importance of integrating seasonal variation in warming temperatures when evaluating the responses to climate warming in multiple developmental stages in oviparous ectotherms.
摘要
气候变暖导致的温度升高存在着时空变异。对于中高纬度的爬行动物而言, 胚胎发育和后代生长经历的变暖温度可能存在季节间差异。而此种季节间差异的变暖温度如何影响后代的适合度, 目前仍然知之甚少。
为了评估季节间差异的变暖温度对胚胎发育和后代发育的独立或交互的影响, 我们以一种寒冷气候区分布的卵生外温物种黑龙江草蜥 (Takydromus amurensis) 为研究对象, 利用2 × 2因子控制的实验方案开展胚胎孵化和幼体饲养等工作 (当前气候与变暖气候胚胎孵化 × 当前气候与变暖气候幼体饲养)。并且, 我们检测了胚胎和幼体发育的指标, 包括孵化成功率、孵化期和幼体初始体长和体重、幼体代谢率、生长率和存活率等。
我们发现, 模拟气候变暖的孵化环境缩短了胚胎的孵化期, 并且孵出的幼体具有更高的存活率。此外, 尽管与当前气候下饲养的幼体在生长率和代谢率上并无差异, 但是在模拟变暖气候下饲养的幼体的存活率得到了显著地提升。从胚胎发育到后代生长阶段均经历变暖温度的幼体, 具有最高的存活率。
本研究揭示了胚胎和幼体均经历中等程度的气候变暖 (RCP 4.5, 1.1–2.6°C) 交互地提升了幼体的适合度, 证明了中等程度的气候变暖可能有益于寒冷气候的卵生外温动物。不仅如此, 本研究也强调了在评估具有多生活史阶段的卵生外温动物对气候变暖的响应时, 考虑季节间温度变暖差异的重要性。
Read the free Plain Language Summary for this article on the Journal blog.
Read the free Plain Language Summary for this article on the Journal blog.
Fusobacterium nucleatum (F. nucleatum, Fn) is associated with the colorectal cancer (CRC). Fn-infection could induce significant levels of serum Fn-specific antibodies in human and mice. The ...objective of this study was to identify Fn-infection that elicit a humoral response in patients with CRC and evaluate the diagnostic performance of serum anti-Fn antibodies. In this work, we showed the mean absorbance value of anti-Fn-IgA and -IgG in the CRC group were significantly higher than those in the benign colon disease group and healthy control group (P < 0.001). The sensitivity and specificity of ELISA for the detection of anti-Fn-IgA were 36.43% and 92.71% based on the optimal cut-off. The combination of anti-Fn-IgA and carcino-embryonic antigen (CEA) was better for diagnosing CRC (Sen: 53.10%, Spe: 96.41%; AUC = 0.848). Furthermore, combining anti-Fn-IgA with CEA and carbohydrate antigen 19-9 (CA19-9) (Sen: 40.00%, Spe: 94.22%; AUC = 0.743) had the better ability to classify CRC patients with stages I-II. These results suggested that Fn-infection elicited high level of serum anti-Fn antibodies in CRC patients, and serum anti-Fn-IgA level may be a potential diagnosing biomarker for CRC. Serum anti-Fn-IgA in combination with CEA and CA19-9 increases the sensitivity of detecting early CRC.
The polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is dysregulated in various cancers, and its upregulation strongly correlates with an invasive phenotype and poor ...prognosis in patients with nasopharyngeal carcinomas. However, the underlying mechanism of Bmi-1-mediated invasiveness remains unknown. In the current study, we found that upregulation of Bmi-1 induced epithelial-mesenchymal transition (EMT) and enhanced the motility and invasiveness of human nasopharyngeal epithelial cells, whereas silencing endogenous Bmi-1 expression reversed EMT and reduced motility. Furthermore, upregulation of Bmi-1 led to the stabilization of Snail, a transcriptional repressor associated with EMT, via modulation of PI3K/Akt/GSK-3beta signaling. Chromatin immunoprecipitation assays revealed that Bmi-1 transcriptionally downregulated expression of the tumor suppressor PTEN in tumor cells through direct association with the PTEN locus. This in vitro analysis was consistent with the statistical inverse correlation detected between Bmi-1 and PTEN expression in a cohort of human nasopharyngeal carcinoma biopsies. Moreover, ablation of PTEN expression partially rescued the migratory/invasive phenotype of Bmi-1-silenced cells, indicating that PTEN might be a major mediator of Bmi-1-induced EMT. Our results provide functional and mechanistic links between the oncoprotein Bmi-1 and the tumor suppressor PTEN in the development and progression of cancer.
Currently, there are no molecular biomarkers for the early detection of non-small-cell lung cancer (NSCLC). This study focused on identifying RNAs found on tumor-educated blood platelets (TEPs) for ...detecting stage I NSCLC.
Platelet RNAs, isolated from the blood of 9 patients with NSCLC (stages I and II) and 8 healthy controls, were analyzed using RNA-seq. ITGA2B was selected as a candidate marker. Two different Polymerase Chain Reactions (PCR) were used to measure ITGA2B in platelet samples from healthy controls (n = 150), patients with NSCLC (n = 243), and patients with benign pulmonary nodules (n = 141) in two cohorts.
Platelet ITGA2B levels were significantly higher (
< 0.001) in patients with NSCLC than in all controls. The diagnostic accuracy of ITGA2B was area under the curve (AUC) of 0.922 95% confidence interval (CI), 0.892-0.952, sensitivity of 92.8%, and specificity of 78.6% in the test cohort and 0.888, 91.2%, and 56.5% in the validation cohort for NSCLC by quantitative real time PCR (q-PCR). Furthermore, ITGA2B maintained diagnostic accuracy for patients with NSCLC using Droplet Digital PCR (ddPCR) and the other type of internal control, Ribosomal Protein L32 (RPL32) ddPCR: 0.967 (0.929-1.000) and RPL32: 0.847(0.773-0.920). A nomogram incorporating ITGA2B, carcinoembryonic antigen (CEA) and stage could predict the overall survival (C-index = 0.756).
TEP ITGA2B is a promising marker to improve identification of patients with stage I NSCLC and differentiate malignant from benign lung nodules.
There is growing opinion that primary spontaneous pneumothorax (PSP) patients without hemodynamic compromise could be safely and successfully managed with observation alone. The aims of this ...meta-analysis were to estimate the safety and effectiveness of conservative treatment compared with that of interventional management as the initial treatment option for patients with PSP.
The PubMed, Embase and Cochrane library databases were systematically searched for randomized controlled trials (RCTs) and cohort studies (prospective or retrospective) until April 25, 2020, that compared conservative treatment and interventional treatment as the initial treatment for patients with PSP. The primary outcomes were success rates and recurrence rates. The secondary outcome was complication rates. Data extraction and quality assessment from eligible studies were independently conducted by two reviewers.
8 trials with a total of 1342 patients were identified. The success rates of conservative management were similar with interventional treatment, with a risk ratio 1.05 (95% confidence interval 0.94 to 1.17, I2 = 69.1%). There was no significant difference of recurrence rates between these two type managements. (RR, 1.43, 95% confidence interval 0.45 to 4.55, I2 = 86.7%). Complication rates were lower in conservative treatment group (13 of 215 6.05%) than in interventional treatment group (57 of 212, 26.89%), although the difference did not reach statistical significance (RR, 0.15, 95% CI, 0.02 to 1.13, I2 = 56.7%).
Results of the meta-analysis suggest that conservative treatment offers a safe and effective alternative as compared with interventional management as the initial treatment approach for patients with PSP. However, more randomized clinical trials are need to provide more strong evidence to confirm our results.
EBV causes B lymphomas and undifferentiated nasopharyngeal carcinoma (NPC). Although the mechanisms by which EBV infects B lymphocytes have been extensively studied, investigation of the mechanisms ...by which EBV infects nasopharyngeal epithelial cells (NPECs) has only recently been enabled by the successful growth of B lymphoma Mo-MLV insertion region 1 homolog (BMI1)-immortalized NPECs in vitro and the discovery that neuropilin 1 expression positively affects EBV glycoprotein B (gB)-mediated infection and tyrosine kinase activations in enhancing EBV infection of BMI1-immortalized NPECs. We have now found that even though EBV infected NPECs grown as a monolayer at extremely low efficiency (<3%), close to 30% of NPECs grown as sphere-like cells (SLCs) were infected by EBV. We also identified nonmuscle myosin heavy chain IIA (NMHC-IIA) as another NPEC protein important for efficient EBV infection. EBV gH/gL specifically interacted with NMHC-IIA both in vitro and in vivo. NMHC-IIA densely aggregated on the surface of NPEC SLCs and colocalized with EBV. EBV infection of NPEC SLCs was significantly reduced by NMHC-IIA siRNA knock-down. NMHCIIA antisera also efficiently blocked EBV infection. These data indicate that NMHC-IIA is an important factor for EBV NPEC infection.
Metabolic reprogramming plays important roles in development and progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism has not been completely defined. In this work, we found ...INSL5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL5 could serve as a novel diagnostic marker for NPC, especially for serum VCA‐IgA‐negative patients. Moreover, higher plasma INSL5 level was associated with poor disease outcome. Functionally, INSL5 overexpression increased, whereas knockdown of its receptor GPCR142 or inhibition of INSL5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo. Mechanistically, INSL5 enhanced phosphorylation and nuclear translocation of STAT5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2‐DG or blockade of INSL5 by a neutralizing antibody reversed INSL5‐induced proliferation and invasion, indicating that INSL5 can be a potential therapeutic target in NPC. In conclusion, INSL5 enhances NPC progression by regulating cancer cell metabolic reprogramming and is a potential diagnostic and prognostic marker as well as a therapeutic target for NPC.
Synopsis
This study reveals that INSL5 promotes tumor progression by regulating cancer cell metabolic reprogramming. INSL5 is a potential diagnostic and prognostic marker as well as a therapeutic target for nasopharyngeal carcinoma (NPC).
INSL5 expression levels are elevated in NPC tumor tissue and in the plasma of NPC patients.
INSL5 plasma levels are associated with NPC patient outcome.
INSL5 promotes tumor progression through an autocrine mechanism involving binding to its receptor GPCR142.
INSL5 activates JAK1‐STAT5 signal pathway and promotes glycolytic gene expression, which in turn induces metabolic reprogramming in cancer cells.
INSL5‐GPCR142 axis can be a potential therapeutic target for NPC.
This study reveals that INSL5 promotes tumor progression by regulating cancer cell metabolic reprogramming. INSL5 is a potential diagnostic and prognostic marker as well as a therapeutic target for nasopharyngeal carcinoma (NPC).
Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, ...platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The
value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222-3.587;
= 0.007) and PLR (HR: 2.003; 95% CI: 1.177-3.410;
= 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (
< 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation-based prognostic scores (
< 0.001). The I stage is a novel and useful predictive factor for OS in patients with NPC.
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