SRY-box transcription factors (SOXs) are effective inducers for the formation of stem-like phenotypes. As a member of SOX family, SOX9 (SRY-box transcription factor 9) has been reported to be highly ...expressed and exert oncogenic functions in multiple human cancers. In this study, we hypothesized that SOX9 could regulate the function of cancer stem/initiating cells (CSCs) to further facilitate the progression of colorectal cancer (CRC). Then, stable transfection of shRNAs was used to silence indicated genes. Loss-of-function experiments were conducted to demonstrate the in vitro function of CRC cells. In vivo study was conducted to determine the changes in tumorigenesis and metastasis in vivo. Bioinformatics analyses and mechanistic experiments were employed to explore the downstream molecules. Presently, GEPIA data indicated that SOX9 was upregulated in 275 COAD (colon adenocarcinoma) samples relative to 349 normal tissues. Besides, we also proved the upregulation of SOX9 in CRC cell lines (HCT15, SW480, SW1116, and HT-29) compared to normal NCM-460 cells. Silencing of SOX9 suppressed cell growth, stemness, migration, and invasion. Mechanistically, SOX9 activated the transcription of lncRNA phenylalanyl-tRNA synthetase subunit alpha antisense RNA 1 (FARSA-AS1), while FARSA-AS1 elevated SOX9 in turn by absorbing miR-18b-5p and augmented FARSA via sequestering miR-28-5p. Furthermore, loss of FARSA-AS1 hindered malignant phenotypes in vitro and blocked tumor growth and metastasis in vivo. Notably, we testified that FARSA-AS1 aggravated the malignancy in CRC by enhancing SOX9 and FARSA. Our study unveiled a mechanism of SOX9-FARSA-AS1-SOX9/FARSA loop in CRC, which provides some clews of promising targets for CRC.
There is increasing evidence that circular RNA (circRNA) are involved in cancer development, but the regulation and function of human circRNA remain largely unknown. In this study, we demonstrated ...that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1mRNA and circZKSCAN1 was significantly lower (P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR (RT‐PCR). The low expression level of ZKSCAN1 was only associated with tumor size (P = 0.032), while the cirZKSCAN1 levels varied in patients with different tumor numbers (P < 0.01), cirrhosis (P = 0.031), vascular invasion (P = 0.002), or microscopic vascular invasion (P = 0.002), as well as with the tumor grade (P < 0.001). Silencing both ZKSCAN1mRNA and circZKSCAN1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro. Silencing or overexpression of both forms of RNA did not interfere with each other. RNA‐seq revealed a very different molecular basis for the observed effects; ZKSCAN1mRNA mainly regulated cellular metabolism, while circZKSCAN1 mediated several cancer‐related signaling pathways, suggesting a nonredundant role for ZKSCAN1mRNA and circRNA. In conclusion, our results revealed two post‐translational products (ZKSCAN1mRNA and circZKSCAN1) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC. cirZKSCAN1 might be a useful marker for the diagnosis of HCC.
Circular RNA have recently been shown to play a regulatory role in disease. We investigated the role of circRNA transcribed from ZKSCAN1, a member of the zinc finger family. Our results revealed two post‐translational products (ZKSCAN1 mRNA and circZKSCAN1) that cooperated closely with one another to inhibit cancer growth migration and invasion, but which affected different signaling pathways.
Over the last decades, imaging technologies have got significant developments and become indispensable in the surgical management of liver cancers. Real-time navigation afforded by intraoperative ...images has a significant impact on the success of liver surgeries. Fluorescence imaging in the near-infrared spectrum has shown potential for tumor detection and image-guided surgery in clinics. While predominantly focused on indocyanine green (ICG) imaging, there is also accelerated development of more specific molecular tracers. Compared to passive targeting contrast agents ICG, active targeting and activatable probes both shed new light for intraoperative navigation owing to the higher degree of specificity for the tumor target. A variety of fluorescence imaging probes have been developed to target biomarkers unique to cancer cells or tumor microenvironment and demonstrated promising results. In this review, we provide a comprehensive update on preclinical development and clinical applications of fluorescence imaging in the surgical management of liver cancers. By highlighting the current status, we aim to offer insight into the challenges and opportunities for further investigation.
For patients with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) after curative resection, the effects of various postoperative adjuvant therapies are not summarized in detail, and ...the comparison between the effects of various adjuvant therapies is still unclear. Thus, we collected existing studies on postoperative adjuvant therapies for patients with HCC with MVI after curative resection and analyzed the effects of various adjuvant therapies.
We collected all studies on postoperative adjuvant therapy for patients with HCC with MVI after curative resection from PubMed, EMBASE, Cochrane Library and SinoMed ending on May 1, 2019. Overall survival (OS) and disease-free/recurrence-free survival (RFS) between each group were compared in these studies by calculating the pooled hazard ratio (HR) and 95% confidence interval (CI). All statistical analyses were assessed by two authors independently.
A total of 13 studies were included in this study, including 824 postoperative adjuvant transarterial chemoembolization (pa-TACE) patients, 90 postoperative radiotherapy patients, 57 radiofrequency ablation (RFA)/re-resection patients, 16 sorafenib patients and 886 postoperative conservative treatment patients. The results showed that pa-TACE significantly improved OS and RFS compared with postoperative conservative treatment in patients with HCC with MVI after curative resection (HR: 0.64, 95% CI: 0.55-0.74, p < 0.001; HR: 0.70, 95% CI: 0.62-0.78, p < 0.001, respectively). There was no significant difference in OS between pa-TACE and radiotherapy in patients with HCC with MVI (HR: 1.75, 95% CI: 0.92-3.32, p = 0.087). RFS in patients with HCC with MVI after pa-TACE was worse than that after postoperative adjuvant radiotherapy (HR: 2.29, 95% CI: 1.43-3.65, p < 0.001). The prognosis of pa-TACE and RFA/re-resection in patients with MVI with recurrent HCC had no significant differences (HR: 0.65, 95% CI: 0.09-4.89, p = 0.671). Adjuvant treatments significantly improved the OS and RFS of patients compared with the postoperative conservative group (HR: 0.580, 95% CI: 0.480-0.710, p < 0.001; HR: 0.630, 95% CI: 0.540-0.740, p < 0.001, respectively).
Compared with postoperative conservative treatment, pa-TACE, postoperative radiotherapy and sorafenib can improve the prognosis of patients with hepatocellular carcinoma with microvascular invasion after curative resection. Postoperative radiotherapy can reduce the recurrence of patients with HCC with MVI after curative resection compared with pa-TACE.
Objective
This study was performed to explore the effective management of bleeding associated with radiofrequency ablation (RFA) of benign thyroid nodules.
Methods
Thirty-five patients with benign ...thyroid nodules who were treated with ultrasound-guided RFA from July 2015 to December 2016 at the Third Affiliated Hospital of Sun Yat-sen University were retrospectively reviewed. The technique efficacy, bleeding, and other complications were assessed during the follow-up period.
Results
The mean technique efficacy was 55.6%±22.8% at 1 month and 24.1%±17.1% at 6 months after the procedure. One case of an intranodular haematoma and two cases of voice change (>1 month) were observed. All patients recovered with corresponding treatment.
Conclusion
Although the incidence of haemorrhage is low, serious haematomas are life-threatening. Therefore, having a comprehensive understanding of the potential complications, an accurate clinical strategy, and adequate technical skills may prevent or help to properly manage these complications.
Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment. Lactic acid (LA) has been identified as an influential factor in promoting immune escape and tumor ...progression. However, the mechanisms through which LA modulates TAMs in colorectal cancer (CRC) remain poorly understood. We used qRT-PCR to quantify the expression of LA-related genes (LDHA and LAMP2) in CRC tumor tissues and adjacent nontumor tissues (n = 64). The biological effects and mechanisms of LA on macrophages and tumors were evaluated via qRT-PCR, Western blot, RNA-seq, wound healing assay, colony formation assay in vitro, and allograft mouse tumor models in vivo. We found the expression of LDHA and LAMP2 was highly elevated in the tumor regions and positively associated with a poor clinical stage of CRC. A high concentration of LA was generated under hypoxia; it could promote tumor progression and metastasis with the involvement of macrophages. The inhibition of LA release impaired this protumor phenomenon. Mechanically, LA induced M2 macrophages through the AKT/ERK signaling pathway; subsequently, M2 macrophages secreted CCL8 and facilitated the proliferation and metastasis of CRC cells by activating the CCL8/CCR5/mTORC1 axis. This effect was inhibited by the antagonist or knockdown of CCR5. In conclusion, lactate-induced CCL8 in TAMs accelerated CRC proliferation and metastasis through the CCL8/CCR5/mTORC1 axis.
Abundant pore space in coal is not only the place for the accumulation of coalbed methane (CBM), but also the tunnel for gas migration. In this study, five sets of coal samples before and after the ...second coalification were selected from the eastern margin of Ordos Basin to simulate supercritical CO
2
(Sc-CO
2
) extraction in supercritical extraction equipment. The evolutions of pore structure and porosity were tested by mercury intrusion porosimetry and nuclear magnetic resonance spectroscopy to compare the changes of pore structure and porosity due to the Sc-CO
2
extraction, and to explain the related mechanism. The results show that: (1) Pore volume, pore specific surface area, and connectivity characteristics changed significantly due to Sc-CO
2
extraction, and the increment of pore volume and pore specific surface area presented a law of increase–decrease–increase with the increase in the coal rank, and the turning point was near the second coalification. (2) The porosity increment change trend due to Sc-CO
2
extraction was increase–decrease–increase with increasing coal rank, and the turning point was again near the second coalification, which supports the mercury intrusion porosimetry results. (3) The changes were observed in the porosity characteristics due to Sc-CO
2
extraction through pore-increasing and expanding effects. Before the second coalification, the pore-increasing and expanding effects co-existed in the micropores, and after the second coalification, the pore-expanding effect mainly existed in the transitional pores and above. (4) The variation model for the pore structure of coal due to Sc-CO
2
extraction was established. The conclusions offer not only important theoretical significance for the CO
2
-enhanced CBM (CO
2
-ECBM) mechanism but also important significance for CO
2
-ECBM engineering.
The dissolution of supercritical carbon dioxide (ScCO2) in water forms a ScCO2–H2O system, which exerts a transformative influence on the physicochemical characteristics of coal and significantly ...impacts the CO2-driven enhanced coalbed methane (CO2-ECBM) recovery process. Herein, the effect of ScCO2–H2O treatment on the physicochemical properties of coal was simulated in a high-pressure reactor. The migration of major elements, change in the pore structure, and change in the CH4 adsorption capacity of coal after the ScCO2–H2O treatment were detected using plasma emission spectroscopy, the low-temperature liquid nitrogen adsorption method, and the CH4 adsorption method, respectively. The results show that (1) the ScCO2–H2O treatment led to mineral reactions causing a significant migration of constant elements in the coal. The migration of Ca ions was the most significant, with an increase in their concentration in treated water from 0 to 16–970 mg·L−1, followed by Na, Mg, and K. Al migrated the least, from 0 to 0.004–2.555 mg·L−1. (2) The ScCO2–H2O treatment increased the pore volume and pore-specific surface area (SSA) of the coal via the dissolution and precipitation of minerals in the coal pores. The total pore volume increased from 0.000795–0.011543 to 0.001274–0.014644 cm3·g−1, and the total pore SSA increased from 0.084–3.332 to 0.400–6.061 m2·g−1. (3) Changes in the CH4 adsorption capacity were affected by the combined effects of a mineral reaction and pore structure change. The dissolved precipitates of the minerals in the coal pores after the ScCO2–H2O treatment caused elemental migration, which not only decreased the mineral content in the coal pores but also increased the total pore volume and total pore SSA, thus improving the CH4 adsorption capacity of the coal. This study provides theoretical support for CO2 sequestration and ECBM recovery.
Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported in many studies to reduce liver fibrosis. Apart from the paracrine mechanism by which the antifibrotic effects of BMSCs inhibit ...activated hepatic stellate cells (HSCs), the effects of direct interplay and juxtacrine signaling between the two cell types are poorly understood. The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated HSCs.
We show here that BMSCs directly cocultured with HSCs significantly suppressed the proliferation and α-smooth muscle actin (α-SMA) expression of HSCs. Moreover, the Notch1 and Hes1 mRNA levels and the Hes1 protein level in cocultured HSCs were evidently higher than in other models. Blocking the Notch signaling pathway with Notch1 siRNA caused the increased expression of phospho-Akt and greater cell growth of cocultured HSCs. This effect was attenuated by the PI3K inhibitor LY294002.
In conclusion, our results demonstrated that BMSCs remarkably inhibited the proliferation of HSCs through a cell–cell contact mode that was partially mediated by Notch pathway activation. In addition, the PI3K/Akt pathway is involved in HSC growth inhibition by the Notch pathway.
These findings demonstrated that BMSCs directly modulate HSCs in vitro via Notch signaling cascades. Our results may provide new insights into the treatment of hepatic fibrosis with BMSCs.
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