NAT10 Promotes Malignant Progression of Lung Cancer via the NF-κB Signaling Pathway.

BACKGROUND: NAT10 (N-acetyltransferase 10) is a newly identified novel acetyltransferase. Abnormal expression of NAT10 is associated with several human disorders, including cancer, autoimmune diseases, and cardiovascular disease. This study aimed to investigate the role of NAT10 in promoting lung cancer malignant progression through the NF-κB (nuclear factor κB) signaling pathway. METHODS: Cells lines BEAS-2B, NCI-H524, A549, PC-9, NCI-H23, and NCI-H258 were cultured for identification. Western blotting and PCR assays determined gene expression within the sample cells. Cellular functionality was assayed using CCK8 (Cell Counting Kit-8), Dual-Luciferase Reporter, and Colony formating. RESULTS: The PCR assay and Western blotting showed a significant elevation of NAT10 levels within tumor tissues compared to paraneoplastic tissues (p < 0.05). Specifically, NAT10 only affected the expression and content of RelA/p65 in lung cancer. Analysis from the TCGA (The Cancer Genome Atlas) database indicated that elevated expression levels of NAT10 in tumors can be a good prognostic indicator for lung cancer patients. The CCK8 assay showed that the knockdown of NAT10 significantly suppressed the A549 cells' progression rate (p < 0.05). The colony formation assays further confirmed that the overexpression of NAT10 significantly increased the generation of clones in the NCI-H524 cells (p < 0.05). The proliferation rate influenced by the overexpression of NAT10 was inhibited by blocking the NF-κB signaling pathway (p < 0.05). Dual-luciferase reporter gene assay results revealed NAT10's potential in promoting the NF-κB signaling pathway's activity in lung cancer. Immunohistochemical staining underscored a strong link between NAT10 protein expression and the NF-κB signaling pathway in lung cancer tissues. CONCLUSIONS: NAT10's expression is significantly upregulated in tumor tissues, supported by PCR results. NAT10 plays a role in the development and proliferation of lung cancer cells and can activate the NF-κB signaling pathway in lung cancer. Hence, NAT10's regulation of the NF-κB signaling pathway is critical in the malignant proliferation of lung cancer.

Targeting Esophageal Squamous Cell Carcinoma by Combining Copper Ionophore Disulfiram and JMJD3/UTX Inhibitor GSK J4.

The alcohol-averse drug disulfiram has been reported to have anti-tumor effects and is well suited for drug combinations. In order to identify potential drug combinations in esophageal squamous cell carcinoma (ESCC), we screened a bioactive compound library with the disulfiram copper chelation product CuET. The Jumonji domain-containing protein 3 (JMJD3) and the ubiquitously transcribed tetratricopeptide repeat protein X-linked (UTX) inhibitor GSK J4 were identified. To further understand the molecular mechanism underlying the efficient drug combination, we applied quantitative mass spectrometry to analyze the signaling pathway perturbation after drug treatment. The data revealed that the synergistic effect of GSK J4 and CuET was due to the interaction among JMJD3 and UTX, which may play important roles in maintaining endoplasmic reticulum (ER) homeostasis in tumor cells. Interestingly, our clinical data analysis showed that high expression of JMJD3 and UTX was associated with T stage and worse prognosis of ESCC patients, further supporting the importance of the above findings. In conclusion, our findings suggest that the combination of CuET and targeting JMJD3/UTX may be a safe, effective, and available treatment for ESCC.

Single-cell sequencing technology applied to epigenetics for the study of tumor heterogeneity.

BACKGROUND: Previous studies have traditionally attributed the initiation of cancer cells to genetic mutations, considering them as the fundamental drivers of carcinogenesis. However, recent research has shed light on the crucial role of epigenomic alterations in various cell types present within the tumor microenvironment, suggesting their potential contribution to tumor formation and progression. Despite these significant findings, the progress in understanding the epigenetic mechanisms regulating tumor heterogeneity has been impeded over the past few years due to the lack of appropriate technical tools and methodologies. RESULTS: The emergence of single-cell sequencing has enhanced our understanding of the epigenetic mechanisms governing tumor heterogeneity by revealing the distinct epigenetic layers of individual cells (chromatin accessibility, DNA/RNA methylation, histone modifications, nucleosome localization) and the diverse omics (transcriptomics, genomics, multi-omics) at the single-cell level. These technologies provide us with new insights into the molecular basis of intratumoral heterogeneity and help uncover key molecular events and driving mechanisms in tumor development. CONCLUSION: This paper provides a comprehensive review of the emerging analytical and experimental approaches of single-cell sequencing in various omics, focusing specifically on epigenomics. These approaches have the potential to capture and integrate multiple dimensions of individual cancer cells, thereby revealing tumor heterogeneity and epigenetic features. Additionally, this paper outlines the future trends of these technologies and their current technical limitations.

Effects of somatostatin in combination with early hemoperfusion on inflammatory, hemorheological and oxidative parameters during the treatment of acute pancreatitis / Efectos de la somatostatina en combinación con hemoperfusión precoz sobre parámetros inflamatorios, hemorreológicos y oxidativos durante el tratamiento de la pancreatitis aguda

Abstract We aimed to evaluate the effects of somatostatin combined with early hemoperfusion on inflammatory and stress responses during acute pancreatitis (AP) treatment. A total of 159 AP patients treated from September 2016 to January 2020 were randomly divided into three groups A-C (n=53). In addition to routine treatment, groups A-C were additionally given somatostatin, early hemoperfusion, and somatostatin combined with early hemoperfusion, respectively. Their inflammatory factors, stress response, intestinal mucosal barrier, hemorheological indices, recovery time, length of stay, clinical efficacy, and adverse reactions were compared. The levels of serum interleukin-10 (IL - 10), catalase and glutathione peroxidase rose in the three groups after ten days of treatment, compared with values before treatment, being the highest rise in group C. The levels of IL -18, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, procalcitonin, high mobility group protein B1, lipid hydrogen peroxide, advanced oxidation protein products, epinephrine, cortisol, D-lactic acid, diamine oxidase, and endotoxin decreased after ten days of treatment compared with those before treatment, which were lowest in group C (P<0.05). After ten days of treatment, the levels of hemorheological indices were significantly lower than those before treatment (P<0.05). Compared with groups A and B, group C had a shorter recovery time of urine amylase, bowel sound and passing gas, remission time of abdominal pain, length of stay, and a higher total response rate (P<0.05). During AP treatment, somatostatin combined with early hemoperfusion effectively relieved inflammatory and stress responses, protected the intestinal mucosal barrier function and improved the hemorheology, thereby promoting the recovery and benefiting the prognosis of patients.

Resumen Nuestro objetivo fue evaluar los efectos de la somatostatina combinada con hemoperfusión temprana sobre las respuestas inflamatorias y de estrés durante el tratamiento de la pancreatitis aguda (PA). Un total de 159 pacientes con PA tratados entre septiembre de 2016 y enero de 2020 se dividieron aleatoriamente en tres grupos A-C (n=53). Con base en el tratamiento de rutina, los grupos A-C recibieron además somatostatina, hemoperfusión temprana y somatostatina combinada con hemoperfusión temprana, respectivamente. Se compararon sus factores inflamatorios, respuesta al estrés, barrera de la mucosa intestinal, índices hemorreológicos, tiempo de recuperación, tiempo de estancia, eficacia clínica y reacciones adversas. Los niveles séricos de interleucina-10 (IL -10), catalasa y glutatión peroxidasa aumentaron en los tres grupos después de 10 días de tratamiento, comparados con los valores antes del tratamiento, siendo más elevados en el grupo C. Los niveles de IL - 18, factor de necrosis tumoral α, molécula de adhesión intercelular 1 soluble, procalcitonina, proteína B1 del grupo de alta movilidad, peróxido de hidrógeno lipídico, los productos proteicos de oxidación avanzada, epinefrina, cortisol, ácido D-láctico, diaminooxidasa y endotoxina disminuyeron después de 10 días de tratamiento en comparación con los previos al tratamiento, que fueron más bajos en el grupo C (P<0,05). Después de 10 días de tratamiento, los índices hemorreológicos fueron significativamente menores que los previos al tratamiento (P<0,05). En comparación con los grupos A y B, el grupo C tuvo un tiempo de recuperación más corto de amilasa en orina, sonido y escape intestinal, tiempo de remisión del dolor abdominal y tiempo de estancia, y una tasa de respuesta total más alta (P<0,05). Durante el tratamiento de la AP, la somatostatina combinada con hemoperfusión precoz alivia eficazmente las respuestas inflamatorias y de estrés, protege la función de la barrera de la mucosa intestinal y mejora la hemorología, favoreciendo la recuperación y beneficiando el pronóstico de los pacientes.

DNAAF5 promotes hepatocellular carcinoma malignant progression by recruiting USP39 to improve PFKL protein stability.

Purposes: Dynein axonemal assembly factor 5 (DNAAF5) is the transcription factor of regulating the cytoskeleton and hydrodynamic protein complex assembly, however, it was not well elucidated in the malignant progression of hepatocellular carcinoma (HCC). Methods: We investigated the role of DNAAF5 in hepatocellular carcinoma by using multiple groups of clinical tissues combined with data from the TCGA database. Then we overexpressed DNAAF5 in hepatocellular carcinoma tumor tissues, which correlates with poor patient survival outcomes. Furthermore, we constructed stable cell lines of HCC cells to confirm the cancer-promoting effects of DNAAF5 in hepatocellular carcinoma. To explore the mechanisms of DNAAF5, transcriptome sequencing combined with mass spectrometry was also performed, which showed that DNAAF5 affects its downstream signaling pathway by interacting with PFKL and that DNAAF5 regulates PFKL protein stability by recruiting the deubiquitination protein, USP39. To corroborate these findings, the same series of tissue microarrays were used to confirm correlations between DNAAF5 and PFKL expressions. In animal experiments, DNAAF5 also promoted the proliferation of HCC cells. Results: We found that DNAAF5 expressions were markedly higher in HCC tissues, compared to the adjacent normal tissues. Increased levels of DNAAF5 were associated with significantly worse prognostic outcomes for HCC patients. Cell function experiments showed that HCC cells of overexpressing DNAAF5 exhibited faster proliferation rates, stronger clone formation abilities and higher drug resistance rates. However, tumor cell proliferation rates and colony formation were significantly decreased after DNAAF5 knockout, accompanied by an increase in sensitivity to sorafenib. In addition, the results of our study showed that DNAAF5 accelerates PFKL protein deubiquitination by recruiting USP39 in HCC cells. Furthermore, The overexpression of DNAAF5 could promote HCC cell proliferation in vivo and in vitro, whereas USP39 knockdown inhibited this effect. Overall, DNAAF5 serves as a scaffold protein to recruit USP39 to form a ternary complex by directly binding the PFKL protein, thereby improving the stability of the latter, which promotes the malignant process of hepatocellular carcinoma. Conclusions: These findings revealed DNAAF5 was negatively correlated with the prognosis of patients with hepatocellular carcinoma. It underlying mechanism showed that DNAAF5 directly binds PFKL and recruits the deubiquitinated protein (USP39) to improve the stability of the PFKL protein, thus enhancing abnormal glycolysis in HCC cells.

Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors.

Cancer is a genetic mutation disease that seriously endangers the health and life of all human beings. As one of the most amazing academic achievements in the past decade, CRISPR/Cas9 technology has been sought after by many researchers due to its powerful gene editing capability. CRISPR/Cas9 technology shows great potential in oncology, and has become one of the most promising technologies for cancer genome-editing therapeutics. However, its efficiency and the safety issues of in vivo gene editing severely limit its widespread application. Therefore, developing a suitable delivery method for the CRISPR/Cas9 system is an urgent problem to be solved at present. Rapid advances in nanomedicine suggest nanoparticles could be a viable option. In this review, we summarize the latest research on the potential use of nanoparticle-based CRISPR/Cas9 systems in cancer therapeutics, in order to further their clinical application. We hope that this review will provide a novel insight into the CRISPR/Cas9 system and offer guidance for nanocarrier designs that will enable its use in cancer clinical applications.

Isolated splenic metastasis of endometrial cancer 12 years after treatment: A case report and literature review.

RATIONALE: The spleen is an uncommon metastatic organ for malignant solid tumors because of its special anatomy and microenvironment. Isolated splenic metastasis of endometrial cancer is an extremely rare clinical event, with only 17 cases reported in literature. PATIENT CONCERNS: We report the case of a 58-year-old woman with abdominal distension and nausea for 7 months who had undergone surgery and chemotherapy for endometrioid adenocarcinoma 12 years previously. A space-occupying lesion in the upper pole of the spleen was observed on an abdominal ultrasound. DIAGNOSIS: The spleen was resected, and splenic metastasis of endometrial adenocarcinoma was histologically confirmed. INTERVENTIONS: Splenectomy was performed, and no lymph nodes or other metastases were observed. The patient received postoperative chemotherapy with 6 cycles of docetaxel and carboplatin. OUTCOMES: The patient recovered well 11 months postoperatively, with no evidence of recurrence or metastatic disease. LESSON: Since the time interval between the diagnosis of primary endometrial cancer and splenic metastasis may be very long, it may be necessary to monitor the recurrence of endometrial cancer after primary treatment.

Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis.

Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis thus holds promise for identifying new therapeutic strategies that may enhance survival. Methods: We applied quantitative mass spectrometry to compare protein expression profiles between primary and metastatic lung cancer cells whilst investigating metastasis-related molecular features. Results: We discovered that BCAT1, the key enzyme in branched-chain amino acid metabolism, is overexpressed at the protein level in metastatic lung cancer cells, as well as in metastatic tissues from lung cancer patients. Analysis of transcriptomic data available in the TCGA database revealed that increased BCAT1 transcription is associated with poor overall survival of lung cancer patients. In accord with a critical role in metastasis, shRNA-mediated knockdown of BCAT1 expression reduced migration of metastatic cells in vitro and the metastasis of these cells to distal organs in nude mice. Mechanistically, high levels of BCAT1 depleted α-ketoglutarate (α-KG) and promoted expression of SOX2, a transcription factor regulating cancer cell stemness and metastasis. Conclusion: Our findings suggest that BCAT1 plays an important role in promoting lung cancer cell metastasis, and may define a novel pathway to target as an anti-metastatic therapy.

Assessment of the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma based on pattern of post-surgical progression.

PURPOSE: To assess the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma and to investigate subgroups of patients suitable for adjuvant radiotherapy. METHODS AND MATERIALS: Data from 785 patients with gastric adenocarcinoma who had undergone D1/D2 radical resection and adjuvant chemotherapy were collected, the site of first progression was determined, and the relationship between the rate of local recurrence and clinicopathologic features was analyzed. RESULTS: By the end of the follow-up period, progression was observed in 405 patients. Local recurrence was observed as the first progression in 161 cases. The local recurrence rate was significantly lower than the non-local progression rate (20.5% vs 31.5%, p=0.007). Multivariate Cox regression analysis showed a significant relationship among degree of differentiation, T stage, N stage, and rate of local recurrence. CONCLUSIONS: Not all patients with gastric carcinoma required adjuvant radiotherapy. However, patients with poorly differentiated cancer cells, advanced T stage (T3/T4), and positive lymph nodes, which included patients in the T4N1-2M0 subgroup, were recommended for adjuvant radiotherapy.

Expression and Clinical Value of LncRNA GAPLINC in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The long noncoding RNA (lncRNA) GAPLINC, or gastric adenocarcinoma predictive long intergenic ncRNA, plays a carcinogenic role in a variety of different tumor types. There is limited information regarding the biological function of GAPLINC in the development of esophageal squamous cell carcinoma (ESCC). METHODS: Surgical tissue samples of 40 patients undergoing ESCC radical surgery were collected, including ESCC tissues and corresponding adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of lncRNA GAPLINC in the human ESCC cell line (TE11). The function role of LncRNA GAPLINC was detected after specific siRNA interference and overexpression in the TE11 cell line. The effects of LncRNA GAPLINC on ESCC cell proliferation, migration and invasion abilities were investigated by flow cytometry, using the Cell Counting Kit-8 (CCK-8), and by Transwell migration assays, respectively. RESULTS: The expression of lncRNA GAPLINC in ESCC tissues was significantly higher than that in corresponding adjacent normal tissues (P<0.05) and correlated with the degree of tumor differentiation (P<0.05). Compared with human esophageal normal epithelial cell lines, the expression of LncRNA GAPLINC was significantly higher in the human ESCC cell line (P<0.05). CCK-8 assays showed that LncRNA GAPLINC overexpression increased the growth rate of cells (P<0.05). Transwell experiments showed that LncRNA GAPLINC overexpression increased the ability of cell migration and invasion compared to control cells (P<0.05). Annexin V assay revealed that LncRNA GAPLINC silencing increased early stage apoptosis (P<0. 05). CONCLUSION: Our results suggest that LncRNA GAPLINC may be used as a biomarker for the diagnosis and monitoring of ESCC, and may play an oncogenic role in ESCC.

Comprehensive analysis of the prognosis and immune infiltration for CXC chemokines in colorectal cancer.

The C-X-C motif (CXC) chemokines are a family of chemotactic molecules that have been identified as potential prognostic markers and prospective therapeutic targets for many kinds of cancer types. Increasing evidence shows that CXC chemokines are associated with the progression of colorectal cancer (CRC); however, the correlations of CXC chemokines with prognostic and immune infiltrates in CRC remain to be clarified. In this study, we analyzed the mRNA expression level, prognostic data and immune infiltrates of CXC chemokines in CRC patients from the Gene Expression Profiling Interactive Analysis, Oncomine, cBioPortal and databases using GeneMANIA, STRING, DAVID 6.8, and TIMER. Our results showed that CXCL1/2/3/4/5/8/9/10/11/13/14/16 were significantly overexpressed in CRC tissues. Furthermore, expression of CXCL1/2/3/9/10/11 was associated with tumor stage in CRC. A significant association was also identified between the co-expression of CXCL16 with EGFR, KRAS and NRAS. In addition, the survival analysis suggested that high CXCL2/3/8/9/10/11/14 expression is correlated with clinical outcomes of CRC patients. Moreover, a significant association was observed between the CXCL8/9/10/11 expression and immune infiltration in colonic and rectal adenocarcinoma. Overall, CXC chemokines are not only implicated as prognostic biomarkers for CRC patients, but may also influence the immune status of CRC tissues.

Circular RNA 0014715 Facilitates Cell Proliferation and Inhibits Apoptosis in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Circular RNAs (circRNAs) have recently been verified to have multiple biological functions and participate in diverse biological processes in different malignant tumors, including esophageal squamous cell carcinoma (ESCC). Nonetheless, the function of circular RNA 0014715 (hsa_circ_0014715, circ_0014715) in ESCC has not been described. MATERIALS AND METHODS: We investigated clinical data from sixty-seven patients undergoing surgery for esophageal cancer. The clinical data were collected. And we analyzed the correlation between the clinical characteristics of these patients and the expression of circ_0014715. Besides, we explored the expression of circ_0014715 in ESCC cell lines. We used cell counting kit-8, colony formation, transwell assay, and flow cytometry to detect changes in cell proliferation, migration, apoptosis, and cell cycle progression. RESULTS: We found that circ_0014715 was highly expressed in esophageal squamous cell carcinoma tissues and cell lines. The correlation analysis of clinicopathological features and gene expression revealed that high expression of circ_0014715 was related to nerve invasion, vascular invasion, more advanced tumor-node-metastasis (TNM) stage and poor differentiation grade. Receiver operating characteristic (ROC) curves revealed that circ_0014715 might have diagnostic value for ESCC. Experiments with cultured cells showed that knockdown of circ_0014715 significantly restrained cell proliferation, migration, invasion, wound healing and accelerated cell apoptosis. And cell cycle arrest at G2 phase was observed via flow cytometry. Overexpression of circ_0014715 caused the opposite effects. Collectively, these studies show that circ_0014715 is closely connected with the pathogenesis and development of ESCC. The excess expression of circ_0014715 may have promoting effects on the progression of esophageal cell carcinoma. CONCLUSION: Our finding revealed that circ_0014715 promoted tumor growth and cell proliferation. All of these suggest that targeting circ_0014715 has potential therapeutic value in the treatment of ESCC.

Knockdown of long non-coding RNA CCAT2 suppresses growth and metastasis of esophageal squamous cell carcinoma by inhibiting the ß-catenin/WISP1 signaling pathway.

OBJECTIVE: Long non-coding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) plays oncogenic roles in several cancers, including esophageal squamous cell carcinoma (ESCC). However, the specific mechanism of how CCAT2 influences ESCC tumorigenesis is still unknown. METHODS: Using RT-qPCR, the mRNA expression levels of CCAT2 in 33 paired ESCC and adjacent non-cancer tissues and cell lines were measured. Lentiviral vector sh-CCAT2 was designed and transfected into TE10 cells. CCK-8 and transwell assays were employed to detect the effects of CCAT2 knockdown on cell proliferation and invasion, respectively. RT-qPCR and western blots were used to detect the effects of CCAT2 knockdown. RESULTS: CCAT2 was overexpressed in ESCC tissues compared with corresponding adjacent tissues. CCAT2 knockdown could suppress cell proliferation and invasion in vitro. Furthermore, knockdown of CCAT2 could suppress the mRNA and protein levels of ß-catenin and Wnt-induced-secreted-protein-1 (WISP1), as well as the mRNA levels of their downstream targets VEGF-A, MMP2, and ICAM-1. High expression of CCAT2 and WISP1 were associated with poor prognosis of ESCC patients. CONCLUSIONS: In conclusion, a novel CCAT2/ß-catenin/WISP1 axis was revealed in ESCC progression and may provide a promising therapeutic target against ESCC. CCAT2 and WISP1 are potential molecular biomarkers for predicting prognosis of ESCC.

High expression of guanine nucleotide-binding protein-like-3-like is associated with poor prognosis in esophageal cancer.

ABSTRACT: Guanine nucleotide-binding protein-like-3-like (GNL3L) is required for processing ribosomal pre-rRNA and cell proliferation and is upregulated in many types of cancer. This study is aimed to investigate the clinical significance of GNL3L in esophageal cancer. The mRNA and protein expression levels of GNL3L were determined by using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. GNL3L was localized in both cytoplasm and nucleus. The expression levels of GNL3L in esophageal cancer tissues were significantly higher than those in adjacent nonmalignant tissues. High GNL3L expression was associated with pathologic type and poor differentiation. Patients with high GNL3L expression had shorter overall survival (OS) than those with low GNL3L expression. Multivariate Cox regression analysis revealed that GNL3L expression was an independently predictive factor for the OS of patient with esophageal cancer. The Gene Expression Profiling Interactive Analysis (GEPIA) databases also showed that GNL3L was upregulated in esophageal cancer, which was closely associated with an unfavorable prognosis of patients with esophageal cancer. Taken together, our findings suggest that GNL3L is upregulated in esophageal cancer, which is linked to the progression of the disease. As a result, GNL3L could be used as a biomarker for esophageal cancer.

YTH Domain Proteins: A Family of m6A Readers in Cancer Progression.

N 6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs). m6A RNA methylation is involved in all stages of RNA life cycle, from RNA processing, nuclear output, translation regulation to RNA degradation, indicating that m6A has various functions affecting RNA metabolism positively or negatively. Reading proteins are vital in regulating the translation and stability of m6A mRNAs positively or negatively. Recent studies have enhanced the understanding of the molecular mechanism of the YT521-B homology (YTH) domain family and the modification of m6A. This study aimed to review the specific mechanisms, functions, and interactions of the YTH domain protein family. It also discussed future research directions, thus providing new ideas for the clinical diagnosis and targeted therapy of cancer.

Au-Pt Nanoparticle Formulation as a Radiosensitizer for Radiotherapy with Dual Effects.

BACKGROUND: Radiotherapy occupies an essential position as one of the most significant approaches for the clinical treatment of cancer. However, we cannot overcome the shortcoming of X-rays which is the high value of the oxygen enhancement ratio (OER). Radiosensitizers with the ability to enhance the radiosensitivity of tumor cells provide an alternative to changing X-rays to protons and heavy ion radiotherapy. MATERIALS AND METHODS: We prepared the Au-Pt nanoparticles (Au-Pt NPs) using a one-step method. The characteristics of the Au-Pt NPs were determined using TEM, HAADF-STEM, elemental mapping images, and DLS. The enhanced radiotherapy was demonstrated in vitro using MTT assays, colony formation assays, fluorescence imaging, and flow cytometric analyses of the apoptosis. The biodistribution of the Au-Pt NPs was analyzed using ICP-OES, and thermal images. The enhanced radiotherapy was demonstrated in vitro using immunofluorescence images, tumor volume and weigh, and hematoxylin & eosin (H&E) staining. RESULTS: Polyethylene glycol (PEG) functionalized nanoparticles composed of the metallic elements Au and Pt were designed to increase synergistic radiosensitivity. The mechanism demonstrated that heavy metal NPs possess a high X-ray photon capture cross-section and Compton scattering effect which increased DNA damage. Furthermore, the Au-Pt NPs exhibited enzyme-mimicking activities by catalyzing the decomposition of endogenous H2O2 to O2 in the solid tumor microenvironment (TME). CONCLUSION: Our work provides a systematically administered radiosensitizer that can selectively reside in a tumor via the EPR effect and enhances the efficiency of treating cancer with radiotherapy.

The novel target of esophageal squamous cell carcinoma: lncRNA GASL1 regulates cell migration, invasion and cell cycle stagnation by inactivating the Wnt3a/ß-catenin signaling.

Long non-coding RNA (lncRNA) Growth-Arrest Associated LncRNA 1 (GASL1) is a lncRNA with a suppressive role in glioma, prostate carcinoma and gastric carcinoma, whereas its involvement in esophageal cancer is unknown. In the present study, we used RT-qPCR to detect the expression of GASL1 in esophageal cancer cell carcinoma (ESCC) cell lines, and constructed the overexpression and interference plasmids of GASL1 and the interference plasmid of DKK1. CCK8 was used to detect the cell proliferation level, clone formation experiment was used to detect the cell clonal formation ability, flow cytometry was used to detect the cell cycle level, and wound healing and Transwell experiments were respectively used to detect the cell invasion and migration. The interference and overexpression plasmids of GASL1 were injected into mice subcutaneously for tumor-bearing experiment. The body weight, tumor growth curve, and tumor weight of mice were recorded, and western blot was used to detect the expression of proliferation-, invasion-, and migration-related proteins and the expression of Wnt3a/ß-catenin signal-related proteins in tumor tissues. LncRNA GASL1 was down-regulated in ESCC cell lines, and GASL1 inhibited ESCC cell progression and regulated cell cycle arrest in ESCC cells. In vivo, GASL1 inhibited tumor growth. GASL1 decreased the protein levels of DDK1, Wnt3a, ß-catenin, and c-MYC in ESCC cell lines. Interfering DKK1 activates Wnt3a/ß--catenin signal to reverse the inhibitory effects of GASL1 on proliferation, cell cycle acceleration, invasion, and migration. In conclusion, lncRNA GASL1 regulates cell migration, invasion and cell cycle stagnation by inactivating the wnt/ß-catenin signaling.

Pretreatment Albumin-to-Fibrinogen Ratio Independently Predicts Chemotherapy Response and Prognosis in Patients with Locally Advanced Rectal Cancer Undergoing Total Mesorectal Excision After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery of total mesorectal excision (TME) is currently accepted as the standard treatment for locally advanced rectal cancer (LARC). This study aimed to investigate the potential prognostic factors, including the albumin-to-fibrinogen ratio (AFR) for LARC patients. METHODS: We retrospectively recruited LARC patients (cT3-4 and/or cN1-2) who underwent nCRT followed by TME between January 2011 and January 2015. The cut-off value of pretreatment AFR for overall survival (OS) was determined by the receiver operating characteristic (ROC) curve. The potential predictive factors for prognosis in the LARC patients were assessed by the univariate and multivariate Cox's proportional hazard regression and Kaplan-Meier curve analyses. RESULTS: AFR was a significant predictor for OS with a cut-off value of 8.65 and an AUC of 0.882 (P<0.001). The pretreatment AFR level was the only independent risk factor for pathologic response to nCRT (HR: 2.44, 95% CI: 1.43-4.17, P=0.003), 5-year OS (HR: 3.31, 95% CI: 1.51-6.77, P=0.005) and disease-free survival (DFS) (HR: 2.73, 95% CI: 1.34-5.47, P=0.007) in LARC patients. A low pretreatment AFR level was significantly associated with a poor 5-year OS and DFS by the Log rank test (P=0.003 and 0.006, respectively). CONCLUSION: Pretreatment AFR level was an independent prognostic factor in LARC patients undergoing TME after nCRT.

Protocadherin 8 (PCDH8) Inhibits Proliferation, Migration, Invasion, and Angiogenesis in Esophageal Squamous Cell Carcinoma.

BACKGROUND Protocadherin 8 (PCDH8) functions as a tumor-suppressor gene in many types of cancer. This study aimed to investigate the role of PCDH8 in esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS Cell proliferation, apoptosis, transwell assay, tube formation assays, and tumor xenograft experiment were performed to explore the role of PCDH8 in the progression of ESCC. RESULTS PCDH8 was found to be downregulated in ESCC cells. Ectopic expression of PCDH8 blocked proliferation, invasion, and migration and induced apoptosis in ESCC cells. Furthermore, vascular endothelial growth factor A (VEGFA) secretion and the AKT signaling pathway were also inhibited when PCDH8 was upregulated. PCDH8 overexpression suppressed epithelial-mesenchymal transition (EMT) and pro-angiogenic activity of ESCC cells. In a mouse model of ESCC xenograft tumors, PCDH8 overexpression remarkably restrained tumor cell growth, with the tumor inhibition rate of 75.2%. PCDH8 was the target of miR-200c and had a negative correlation with miR-200c. CONCLUSIONS PCDH8 exerts a tumor-suppressive effect against ESCC cells. However, further studies are required to elucidate the exact molecular mechanism underlying the antitumor activity of PCDH8 in ESCC.

P53-regulated lncRNA uc061hsf.1 inhibits cell proliferation and metastasis in human esophageal squamous cell cancer.

The expression of long noncoding RNAs (lncRNAs) is closely associated with cancer development and progression, making these lncRNAs potentially novel therapeutic targets. In this study, we aimed to explore the potential function of lncRNA-uc061hsf.1 in esophageal squamous cell carcinoma (ESCC). The expression of lncRNA-uc061hsf.1 in ESCC tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, and metastasis were detected via CCK-8, flow cytometry, and Transwell assays. The interaction between p53 and lncRNA uc061hsf.1 was analyzed using luciferase reporter gene and qRT-PCR. Through this approach, we identified the novel lncRNA uc061hsf.1, which was expressed in low level in ESCC and was correlated with lymph node metastasis and poor differentiation in ESCC patients. Knockdown or overexpression of lncRNA uc061hsf.1 in ESCC cells promoted or inhibited cell proliferation and metastasis, respectively. Mechanistically, lncRNA uc061hsf.1 was induced by p53, and luciferase reporter gene confirmed that lncRNA uc061hsf.1 was a direct transcriptional target of p53. We further found that uc061hsf.1 was able to regulate expression of the transcription factor FoxA1, thereby potentially influencing tumor cell migration. In conclusion, these results suggest that p53-regulated lncRNA uc061hsf.1 is a cancer suppressor gene which is associated with tumor progression in ESCC.