Nadir CA-125 level as prognosis indicator of high-grade serous ovarian cancer

PURPOSE: The capacity of nadir CA-125 levels to predict the prognosis of epithelial ovarian cancer remains controversial. This study aimed to explore whether the nadir CA-125 serum levels could predict the durations of overall survival (OS) and progression free survival (PFS) in patients with high-grade serous ovarian cancer (HG-SOC) from the USA and PRC. MATERIALS AND METHODS: A total of 616 HG-SOC patients from the MD Anderson Cancer Center (MDACC, USA) between 1990 and 2011 were retrospectively analyzed. The results of 262 cases from the Jiangsu Institute of Cancer Research (JICR, PRC) between 1992 and 2011 were used to validate the MDACC data. The CA-125 immunohistochemistry assay was performed on 280 tissue specimens. The Cox proportional hazards model and the log-rank test were used to assess the associations between the clinicopathological characteristics and duration of survival. RESULTS: The nadir CA-125 level was an independent predictor of OS and PFS (p < 0.01 for both) in the MDACC patients. Lower nadir CA-125 levels (≤10 U/mL) were associated with longer OS and PFS (median: 61.2 and 16.8 months with 95% CI: 52.0–72.4 and 14.0–19.6 months, respectively) than their counterparts with shorter OS and PFS (median: 49.2 and 10.5 months with 95% CI: 41.7–56.7 and 6.9–14.1 months, respectively). The nadir CA-125 levels in JICR patients were similarly independent when predicting the OS and PFS (p < 0.01 for both). Nadir CA-125 levels less than or equal to 10 U/mL were associated with longer OS and PFS (median: 59.9 and 15.5 months with 95% CI: 49.7–70.1 and 10.6–20.4 months, respectively), as compared with those more than 10 U/mL (median: 42.0 and 9.0 months with 95% CI: 34.4–49.7 and 6.6–11.2 months, respectively). Baseline serum CA-125 levels, but not the CA-125 expression in tissues, were associated with the OS and PFS of HG-SOC patients in the MDACC and JICR groups. However, these values were not independent. Nadir CA-125 levels were not associated with the tumor burden based on second-look surgery (p = 0.09). Patients who achieved a pathologic complete response had longer OS and PFS (median: 73.7 and 20.7 months with 95% CI: 63.7–83.7 and 9.5–31.9 months, respectively) than those with residual tumors (median: 34.6 and 10.6 months with 95% CI: 6.9–62.3 and 4.9–16.3 months, respectively). CONCLUSIONS: The nadir CA-125 level was an independent predictor of OS and PFS in HG-SOC patients. Further prospective studies are required to clinically optimize the chances for a complete clinical response of HG-SOC cases with higher CA-125 levels (>10 U/mL) at the end of primary treatment

CORO1C is Associated With Poor Prognosis and Promotes Metastasis Through PI3K/AKT Pathway in Colorectal Cancer

Trophoblast cell surface protein 2 (Trop2) is one of the cancer-related proteins that plays a vital role in biological aggressiveness and poor prognosis of colorectal cancer (CRC). The study of the Trop2 related network is helpful for us to understand the mechanism of tumorigenesis. However, the effects of the related proteins interacting with Trop2 in CRC remain unclear. Here, we found that coronin-like actin-binding protein 1C (CORO1C) could interact with Trop2 and the expression of CORO1C in CRC tissues was higher than that in paracarcinoma tissues. The expression of CORO1C was associated with histological type, lymph node metastasis, distant metastasis, AJCC stage, venous invasion, and perineural invasion. The correlation between CORO1C expression and clinical characteristics was analyzed demonstrating that high CORO1C expression in CRC patients were associated with poor prognosis. Furthermore, CORO1C knockdown could decrease the cell proliferation, colony formation, migration and invasion in vitro and tumor growth in vivo. The underlying mechanisms were predicted by bioinformatics analysis and verified by Western blotting. We found that PI3K/AKT signaling pathway was significantly inhibited by CORO1C knockdown and the tuomr-promoting role of CORO1C was leastwise partly mediated by PI3K/AKT signaling pathway. Thus, CORO1C may be a valuable prognostic biomarker and drug target in CRC patients

Heavy metal migration and risk transference associated with cyanobacterial blooms in eutrophic freshwater

The distribution of metals in cyanobloom-forming lakes, and potential risks of these metals during irrigation with water derived from the bloom were evaluated in this study. Seven metals were monitored throughout a cyanobacterial bloom season in Lake Taihu. Cyanobloom bio-dilution of the targeted metals could be explained by the negative relationships between total phytoplankton metal contents (Cu, Fe, Zn, Pb and Cr) and Chl a concentrations (p &lt; 0.05). Meanwhile, the ratios of extracellular bound to total cellular bound metals (Cu, Zn, Pb, Cr and Cd) were positively correlated with the ratios of cyanophyta to total phytoplankton (p &lt; 0.01), indicating the enhanced extracellular bound of these metals during cyanobloom period. Secondly, Cd, Pb and Cr were detected in several local vegetables. In comparison to reference vegetables, vegetables (e.g., radish, soybean, and cowpea), which were irrigated with cyanobloom broth collected from Lake Taihu, presented high health risk index (HRI) and were not safe for human consumption. Collectively, the frequent dominant colonial Microcystis blooms which performed high metal affinity might mediate the distribution of heavy metals in lake and potentially transferred these pollutants into terrestrial system. (C) 2017 Published by Elsevier B.V.</p

Distinct DNA Methylomes of Human Placentas Between Pre-Eclampsia and Gestational Diabetes Mellitus

Background: The placenta acts not only as a conduit of nutrient and waste exchange between mother and developing fetus but also functions as a regulator of the intrauterine environment. Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are leading causes of complications during pregnancy. Pathophysiologies show that they are associated with one another. Epigenetics provides a link between environmental factors that have previously been linked to poor pregnancy outcomes and fetal programming. Methods and Results: The present study investigated genome-wide DNA methylation changes in PE and GDM compared with control subjects through DNA methylation microarray. We found that the methylation patterns of placentas from PE and GDM women were similar; 64.4% of the annotated genes with differential methylation presented concordant changes between PE and GDM patients. Significantly, the same functional processes were affected by PE and GDM, with cell adhesion and cell differentiation being the most populated clusters and including genes related to carbohydrate metabolism and lipid metabolism. Conclusion: Our work showed that of DNA methylation patterns in human placentas are reliably and significantly associated with PE and GDM. DNA methylation status in the human placenta can function as a marker for the intrauterine environment and potentially play a functional role in PE and GDM development

In situ amplification based on assembly of aptamer sandwiches on nanochannels for ultrasensitive detection of exosomes

Exosomes hold tremendous potential as promising biomarkers for the early diagnosis of cancer. The urgent need for sensitive identification of cancer cell-derived exosomes has emphasized the importance of fabricating innovative approaches. In this work, we propose a novel in situ amplification strategy for ultrasensitive detection of cancer cell-derived exosomes based on the assembly of aptamer sandwiches on nanochannels. Specifically, the nanochannels are functionalized with aptamers targeting the transmembrane receptor protein CD63 to enable selective capture of exosomes. Meanwhile, the aptamers specific to membrane protein EpCAM are employed as anchors for binding with the targeted exosomes. This orchestrated interaction leads to the assembly of aptamer sandwiches, initiating a TdT-mediated polymerization reaction, thereby facilitating in situ amplification. Consequently, ultrasensitive, highly specific, and accurate detection of exosomes can be achieved, with a linear detection range from 2.06 × 103 to 2.06 × 108 particles/mL and a detection limit as low as 6.87 × 102 particles/mL. Moreover, the method shows satisfactory anti-interference capacity for the detection of exosomes in real serum samples, indicating potential applications in early clinical diagnosis of cancer

Mechanisms by which the intestinal microbiota affects gastrointestinal tumours and therapeutic effects

Abstract The intestinal microbiota is considered to be a forgotten organ in human health and disease. It maintains intestinal homeostasis through various complex mechanisms. A significant body of research has demonstrated notable differences in the gut microbiota of patients with gastrointestinal tumours compared to healthy individuals. Furthermore, the dysregulation of gut microbiota, metabolites produced by gut bacteria, and related signal pathways can partially explain the mechanisms underlying the occurrence and development of gastrointestinal tumours. Therefore, this article summarizes the latest research progress on the gut microbiota and gastrointestinal tumours. Firstly, we provide an overview of the composition and function of the intestinal microbiota and discuss the mechanisms by which the intestinal flora directly or indirectly affects the occurrence and development of gastrointestinal tumours by regulating the immune system, producing bacterial toxins, secreting metabolites. Secondly, we present a detailed analysis of the differences of intestinal microbiota and its pathogenic mechanisms in colorectal cancer, gastric cancer, hepatocellular carcinoma, etc. Lastly, in terms of treatment strategies, we discuss the effects of the intestinal microbiota on the efficacy and toxic side effects of chemotherapy and immunotherapy and address the role of probiotics, prebiotics, FMT and antibiotic in the treatment of gastrointestinal tumours. In summary, this article provides a comprehensive review of the pathogenic mechanisms of and treatment strategies pertaining to the intestinal microbiota in patients with gastrointestinal tumours. And provide a more comprehensive and precise scientific basis for the development of microbiota-based treatments for gastrointestinal tumours and the prevention of such tumours

Comparative Proteomic Profile of the Human Umbilical Cord Blood Exosomes between Normal and Preeclampsia Pregnancies with High-Resolution Mass Spectrometry

Background/Aims: Exosomes are extracellular vesicles that are involved in several biological processes. The roles of proteins from human umbilical cord blood exosomes in the pathogenesis of preeclampsia remains poorly understood. Methods: In this study, we used high-resolution LC-MS/MS technologies to construct a comparative proteomic profiling of human umbilical cord blood exosomes between normal and preeclamptic pregnancies. Results: A total of 221 proteins were detected in human umbilical cord blood exosomes, with 14 upregulated and 15 downregulated proteins were definitively identified between preeclamptic and control pregnancies. Further bioinformatics analysis (Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis) indicated that these differentially expressed proteins correlate with enzyme regulator activity, binding, extracellular region, cell part, biological regulation, cellular process and complement and coagulation cascades occurring during pathological changes of preeclampsia. Conclusion: Our results show significantly altered expression profiles of proteins in human umbilical cord blood exosomes between normal and preeclampsia pregnancies. These proteins may be involved in the etiology of preeclampsia

Amorphous WO3WO_{3} Induced Lattice Distortion for a Low-Cost and Highly-Efficient Electrocatalyst for Overall Water Splitting in Acid

The development of highly active and durable catalysts for water oxidation under acidic conditions is necessary but challenging for renewable energy conversion. Ir-based catalysts are highly efficient for water oxidation in acid, but their large scale application is hindered by the high cost and scarcity of iridium. Herein, we use an amorphous WO$_3$ induced lattice distortion (AWILD) strategy to reduce the Ir content to only 2 wt% in the final material. The optimized hybrid nitrogen-doped carbon (NC)/WO$_3$/IrO$_2$ can efficiently catalyze water oxidation with a low overpotential of 270 mV at 10 mA cm$^{−2}$ current density $(η_{10})$ and a high turnover frequency of over 2 s$^{−1}$ at 300 mV overpotential in 0.5 M H$_2$SO$_4$, a performance that surpasses that of commercial IrO$_2$ significantly. Introducing the layer of amorphous WO$_3$ between IrO$_2$ nanoparticles and NC can distort the lattice of IrO$_2$, exposing more highly active sites for water oxidation. The AWILD effect compensates for the lower Ir content and dramatically reduces the cost of the catalyst without sacrificing the catalytic activity. Additionally, this catalyst also exhibits high activity in acid for hydrogen evolution with only 65 mV of $η_{10}$ attributed to the AWILD effect, exhibiting efficient bifunctionality as a Janus catalyst for overall water splitting. The AWILD approach provides a novel and efficient strategy for low-cost and highly efficient electrocatalysts for acidic overall water splitting with an extremely low content of noble metals

Association between BANCR and clinicopathological parameters of patients.

<p>Association between BANCR and clinicopathological parameters of patients.</p