Biomarkers of lymph node metastasis in colorectal cancer: update.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally, trailing only behind lung cancer, and stands as the third most prevalent malignant tumor, following lung and breast cancers. The primary cause of mortality in colorectal cancer (CRC) stems from distant metastasis. Among the various routes of metastasis in CRC, lymph node metastasis predominates, serving as a pivotal factor in both prognostication and treatment decisions for patients. This intricate cascade of events involves multifaceted molecular mechanisms, highlighting the complexity underlying lymph node metastasis in CRC. The cytokines or proteins involved in lymph node metastasis may represent the most promising lymph node metastasis markers for clinical use. In this review, we aim to consolidate the current understanding of the mechanisms and pathophysiology underlying lymph node metastasis in colorectal cancer (CRC), drawing upon insights from the most recent literatures. We also provide an overview of the latest advancements in comprehending the molecular underpinnings of lymph node metastasis in CRC, along with the potential of innovative targeted therapies. These advancements hold promise for enhancing the prognosis of CRC patients by addressing the challenges posed by lymph node metastasis.

Molecular Insights into the Specific Targeting of c-MYC G-Quadruplex by Thiazole Peptides.

Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.

The gut microbiota metabolite butyrate mitigates MPTP/MPP+ -induced Parkinson's disease by inhibiting the JAK2/STAT3 signaling pathway.

Butyrate (BU), a gut microbiota-derived metabolite, has been reported to play a neuroprotective role in Parkinson's disease (PD). However, the specific molecular mechanism of BU has not been fully interpreted. This work aimed to verify the protective effects of BU against MPTP/MPP+ -induced neurotoxicity and explore the mechanisms involved. The results showed that BU protected against MPTP-induced motor dysfunction and decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels. Additionally, BU pretreatment improved PC12 cell viability and reduced MPP+ -induced PC12 cell apoptosis. BU treatment also attenuated MPP+ -stimulated oxidative stress and inflammatory response in PC12 cells. Furthermore, BU inhibited MPTP/MPP+ -induced hyperactivation of the JAK2/STAT3 signaling in mice and PC12 cells. Besides, a JAK2 agonist, Coumermycin A1 (C-A1), substantially reversed BU-mediated inhibition on JAK2/STAT3 phosphorylation in MPP+ -challenged PC12 cells and abated BU-induced repression on MPP+ -triggered apoptosis, oxidative stress, and inflammatory response in PC12 cells. To sum up, BU might exert neuroprotective effects against MPP+ /MPTP-induced neurotoxicity by inactivating the JAK2/STAT3 signaling.

Long noncoding RNA BBOX1-AS1 increased radiotherapy sensitivity in colorectal cancer by stabilizing and activating PFK1.

PURPOSE: Our study explored the effect of long noncoding RNA BBOX1-AS1 on colorectal cancer (CRC) radiosensitivity in vivo and in vitro. METHODS: Differentially expressed lncRNAs in CRC were screened using a bioinformatics database and an online prediction website. The expression of BBOX1-AS1 in tissue samples was analyzed via real-time quantitative PCR (RT-qPCR). Subcellular localization of BBOX1-AS1 in CRC cells was analyzed using fluorescence in situ hybridization (FISH). The correlation between BBOX1-AS1 and PFK1 expression levels in CRC tissues was analyzed via Pearson's correlation coefficient. The effect of BBOX1-AS1 on PFK1 stability was investigated using RNA and protein stability testing. RNA Binding Protein Immunoprecipitation (RIP) and RNA pull-down assays were used to confirm the binding of BBOX1-AS1 to PFK1. RESULTS: BBOX1-AS1 was highly expressed in CRC and associated with poor prognosis. Similarly, it was highly expressed in CRC tissues and CRC cell lines. In addition, BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells and inhibited apoptosis. RIP and RNA pull-down experiments confirmed that BBOX1-AS1 bound to PFK1. RNA stability and protein stability experiments showed that BBOX1-AS1 affected the stability of PFK1 mRNA and protein. Furthermore, we confirmed that BBOX1-AS1 increased radiation resistance through the regulation of PFK1 expression. CONCLUSIONS: BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells through stabilization of the expression of PFK1. BBOX1-AS1 also inhibited CRC cell apoptosis and increased radiotherapy resistance in CRC cells.

Potential prognostic and therapeutic value of ANXA8 in renal cell carcinoma: based on the comprehensive analysis of annexins family.

BACKGROUND: Annexins are a family of proteins involved in a wide variety of cellular processes such as inflammation, proliferation, differentiation, apoptosis, migration and membrane repair. However, the role of most Annexins in renal cell carcinoma (RCC) remained unclear. METHODS: The differentially expressed Annexins in RCC compared with normal controls were screened applying the TCGA database. The correlation of differentially expressed Annexins with clinical stages, grades and overall survival was analyzed to explore the clinical significance of Annexins in RCC. Then ANXA8 was selected and further stained in the discover and validation RCC cohort. The correlation of ANXA8 expression with clinical parameter was verified at the protein level. To explore the potential function of ANXA8, ANXA8 was knockdown in the RCC cell line and further analyzed using transcriptome and bioinformatic analysis. RESULTS: mRNA expression of ANXA1, ANXA2R, ANXA4, ANXA8, ANXA8L1 and ANXA13 were significantly upregulated in RCC compared with normal kidney tissues. In contrast, ANXA3 and ANXA9 mRNA expression was significantly downregulated. Higher expression of ANXA2R, ANXA8 and ANXA8L1 were correlated with worse overall survival, while lower expression of ANXA3, ANXA9 and ANXA13 were associated with worse clinical outcomes in RCC patients. We further demonstrated that ANXA8 expression was significantly increased in RCC compared with normal renal tissues at the protein level. And higher protein expression of ANXA8 was associated with higher clinical grades. Through the bioinformatics analysis and cell cycle analysis, we found knockdown of ANXA8 mainly influenced the cell cycle and DNA replication. The top ten hub genes consist of CDC6, CDK2, CHEK1, CCNB1, ORC1, CHEK2, MCM7, CDK1, PCNA and MCM3. CONCLUSIONS: Multiple members of Annexins were abnormally expressed and associated with the prognosis of RCC. The expression of ANXA8 was significantly increased in RCC and associated with poor prognosis. ANXA8 might influence the cell cycle and could be a potential biomarker and therapeutic target for RCC.

[Effectiveness of autologous hematopoietic stem cell transplantation in the treatment of high-risk neuroblastoma in children: a single-center clinical study]. / å•ä¸­å¿ƒå„¿ç«¥é«˜å±ç¥žç»æ¯ç»†èƒžç˜¤è‡ªä½“é€ è¡€å¹²ç»†èƒžç§»æ¤çš„ç–—æ•ˆåˆ†æž.

OBJECTIVES: To investigate the effectiveness of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) in the treatment of children with high-risk neuroblastoma (NB). METHODS: A retrospective analysis was performed on 29 children with high-risk NB who were admitted to Shanghai Children's Hospital and were treated with high-dose chemotherapy combined with ASCT from January 2013 to December 2021, and their clinical features and prognosis were analyzed. RESULTS: Among the 29 children treated by high-dose chemotherapy combined with ASCT, there were 18 boys (62%) and 11 girls (38%), with a median age of onset of 36 (27, 59) months. According to the International Neuroblastoma Staging System, 6 children (21%) had stage III NB and 23 children (79%) had stage IV NB, and the common metastatic sites at initial diagnosis were bone in 22 children (76%), bone marrow in 21 children (72%), and intracalvarium in 4 children (14%). All 29 children achieved reconstruction of hematopoietic function after ASCT. After being followed up for a median time of 25 (17, 45) months, 21 children (72%) had continuous complete remission and 8 (28%) experienced recurrence. The 3-year overall survival rate and event-free survival rate were 68.9%±16.1% and 61.4%±14.4%, respectively. Presence of bone marrow metastasis, neuron-specific enolase ≥370 ng/mL and positive bone marrow immunophenotyping might reduce the 3-year event-free survival rate (P<0.05). CONCLUSIONS: Children with high-risk NB who have bone marrow metastasis at initial diagnosis tend to have a poor prognosis. ASCT combined with high-dose chemotherapy can effectively improve the prognosis of children with NB with a favorable safety profile.

Decreased salivary α-amylase activity responding to citric acid stimulation in Myasthenia gravis with malnutrition.

OBJECTIVES: Malnutrition, defined according to Nutritional risk screening (NRS 2002), is commonly observed in patients of Myasthenia gravis (MG), a neuromuscular disorder manifested by varied degrees of skeletal muscle weakness. Because biochemical composition of saliva changes in correspondence to alterations in nutritional status, we tested our hypothesis that a certain saliva component(s) might serve as a biomarker(s) for nutrition status of MG, particularly for those MG patients with high risk of malnutrition. MATERIALS AND METHODS: 60 MG patients and 60 subjects belonging to the healthy control group (HCG) were enrolled in this case-control study. The salivary α-amylase (sAA) activity, salivary flow rate (SFR), pH, total protein density (TPD), and the concentrations of chloride and calcium ions in MG group with or without malnutrition were measured before and after citric acid stimulation. Thereafter, the relationship between sAA activity and BMI was determined in MG and HCG. RESULTS: Compared with HCG, more patients with malnutrition, increased TPD and chloride and calcium concentrations but decreased pH value and SFR both before and after acid stimulation, as well as reduced sAA activity, pH and TPD responses to acid stimulation. MG with malnutrition showed decreased sAA activity and TPD responding to acid stimulation compared with those without malnutrition. Compared with normal BMI, sAA activity response to acid stimulation was reduced in low BMI. There was a significant strong positive correlation between the ratio of sAA activity and BMI in MG. CONCLUSIONS: Salivary biochemical characteristics are abnormally altered in MG with malnutrition. Altered sAA activity responding to acid stimulation was associated with malnutrition. CLINICAL RELEVANCE: Decreased sAA activity responding to acid stimulation can reflect malnutrition state and may be one potential screening marker for MG patients with high risk of malnutrition.

Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells.

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3ß was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.

SiRNA targeting PFK1 inhibits proliferation and migration and enhances radiosensitivity by suppressing glycolysis in colorectal cancer.

PURPOSE: This study explored the effects of phosphofructokinase-1 (PFK1) on the radiosensitivity of colorectal cancer (CRC) in vivo and in vitro and the underlying mechanisms. METHODS: Tissue samples from 48 patients with rectal cancer who had received neoadjuvant radiotherapy followed by surgery were analyzed. The expression of PFK1 in tissue samples was semi-quantitated by immunohistochemistry, and its relationship with clinicopathological features was analyzed. The effects of PFK1 knockdown on the survival, apoptosis, migration, and radiosensitivity of CRC cells were evaluated. Glycolysis-related indicators were used to examine glycolytic activity. The effects of PFK1 on the radiosensitivity of CRC in vivo were assessed by measuring tumor formation in nude mice. RESULTS: PFK1 was overexpressed in rectal cancer and was higher in radiation-resistant tumors than in radiation-sensitive tumors. SiRNA-induced PFK1 silencing increased apoptosis and inhibited migration and proliferation of CRC cells. Knockdown of PFK1 made the CRC cells sensitive to ionizing radiation in vivo. Oligomycin partially restored the expression of PFK1, enhanced glycolysis, and reversed the enhanced radiosensitivity of CRC cells induced by siRNA-PFK1. Downregulation of PFK1 combined with irradiation inhibited growth of nude mice xenografts, which was related to an increase in apoptosis. CONCLUSIONS: Our study indicates that high expression of PFK1 is negatively correlated with radiosensitivity in CRC and likely accelerates the proliferation and migration of CRC cells. Downregulation of PFK1 may enhance the radiosensitivity of CRC cells in vivo and in vitro by inhibiting glycolysis.

Bidirectional Relationship Between Primary Sjögren Syndrome and Non-Hodgkin Lymphoma: A Nationwide Taiwanese Population-based Study.

OBJECTIVE: Bidirectional relationships between some autoimmune diseases and non-Hodgkin lymphoma (NHL) may exist. We conducted this nationwide population-based study in Taiwan to investigate whether there is a bidirectional relationship between primary Sjögren syndrome (pSS) and NHL. METHODS: Using the National Health Insurance Research Database of Taiwan, we identified 15,636 patients with new-onset pSS without previous cancer and 25,074 patients with new-onset NHL without previous pSS as 2 non-overlapping cohorts from 1998 to 2012, and followed them until 2013. Standardized incidence ratios (SIR) for NHL in the patients with pSS and SIR for pSS in the patients with NHL were compared with the general population. RESULTS: Among the 15,636 patients with pSS, 741 developed cancers, including 51 with NHL. The highest SIR of specific cancer risk in patients with pSS was that for NHL (SIR 4.6, 95% CI 3.4-6.0). Among the 25,074 patients with NHL, 49 developed pSS; the SIR was also increased (SIR 3.2, 95% CI 2.4-4.2). The risk was highest within 1 year after the diagnosis of each disease. CONCLUSION: This nationwide population-based study is the first to report a bidirectional relationship between pSS and NHL. Our findings suggest being alert for patients with pSS or NHL who have early signs of the other disease in clinical care. The underlying mechanisms of the bidirectional relationship merit further investigation.

Identification of new hypoxia-regulated epithelial-mesenchymal transition marker genes labeled by H3K4 acetylation.

Hypoxia-induced epithelial-mesenchymal transition (EMT) involves the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5. The histone mark histone 3 lysine 4 acetylation (H3K4Ac) is observed in the promoter regions of various EMT marker genes (eg, CDH1 and VIM). To further define the genome-wide location of H3K4Ac, a chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) analysis was performed using a head and neck squamous cell carcinoma (HNSCC) FaDu cell line under normoxia and hypoxia. H3K4Ac was found to be located mainly around the transcription start site. Coupled with analysis of gene expression by RNA sequencing and using a HDAC3 knockdown cell line, 10 new genes (BMI1, GLI1, SMO, FOXF1, SIRT2, etc) that were labeled by H3K4Ac and regulated by HDAC3 were identified. Overexpression or knockdown of GLI1/SMO increased or repressed the in vitro migration and invasion activity in OECM-1/FaDu cells, respectively. In HNSCC patients, coexpression of GLI1 and SMO in primary tumors correlated with metastasis. Our results identify new EMT marker genes that may play a significant role in hypoxia-induced EMT and metastasis and further provide diagnostic and prognostic implications.

Facile Synthesis of Urchin-Like and Bouquet-Like Silver Nanoparticles Using Gas Assisted Wet Chemistry Method.

A facile synthesis approach of urchin-like and bouquet-like silver nanoparticles (AgNPs) using gas assisted wet chemistry method with silver nitride as source materials, ascorbic acid as reducing agent, polyvinylpyrrolidone (PVP) as passivator and NO2/O2 as ventilation mixture is proposed It was demonstrated that the urchin-like and bouquet-like AgNPs evolved from spherical nanoparti cles and/or clusters of Ag as a result of strong adsorption and passivation of newly-formed Ag {100} facets by PVP, which effectively boost preferential growth. The NO2/O2 as the ventilation mixture provides an equilibrium of aggregation and detachment of Ag atoms on the surface, thus confining the shapes of AgNPs generated. This study provides an alternative approach for synthesis AgNPs in specific shapes and facilitates their applications.

Bidirectional relationship between systemic lupus erythematosus and non-Hodgkin's lymphoma: a nationwide population-based study.

OBJECTIVES: We conducted this nationwide population-based study in Taiwan to investigate whether there is a bidirectional relationship between SLE and non-Hodgkin's lymphoma (NHL). METHODS: Using the National Health Insurance Research Database of Taiwan, we identified 16 417 patients with new-onset SLE without previous cancer and 25 069 patients with new-onset NHL without previous SLE as two non-overlapping cohorts from 1998-2012, and followed them until 2013. Standardized incidence ratio (SIR) for NHL in the patients with SLE and SIR for SLE in the patients with NHL were compared with the general population. RESULTS: Among the 16 417 patients with SLE, 512 developed cancers, including 34 with NHL. The highest SIR was that for NHL (SIR 4.2, 95% CI 2.9, 5.9) in site-specific cancer risk analysis. Among the 25 069 patients with NHL, 14 developed SLE, and the SIR was also increased (SIR 2.0, 95% CI 1.1, 3.4). The SIRs of the patients with SLE to develop NHL and the patients with NHL to develop SLE were both highest within the first year after the diagnosis of each disease. CONCLUSION: This nationwide population-based study is the first study to report a bidirectional relationship between SLE and NHL. This finding may suggest being alert for the patients with SLE or NHL who have early sings of the other disease in clinical care.

Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview.

Cancer is a disease caused by the accumulation of genetic and epigenetic changes in two types of genes: tumor suppressor genes (TSGs) and proto-oncogenes. Extensive research has been conducted over the last few decades to elucidate the role of TSGs in cancer development. In cancer, loss of TSG function occurs via the deletion or inactivation of two alleles, according to Knudson's two-hit model hypothesis. It has become clear that mutations in TSGs are recessive at the level of an individual cell; therefore, a single mutation in a TSG is not sufficient to cause carcinogenesis. However, many studies have identified candidate TSGs that do not conform with this standard definition, including genes inactivated by epigenetic silencing rather than by deletion. In addition, proteasomal degradation by ubiquitination, abnormal cellular localization, and transcriptional regulation are also involved in the inactivation of TSGs. This review incorporates these novel additional mechanisms of TSG inactivation into the existing two-hit model and proposes a revised multiple-hit model that will enable the identification of novel TSGs that can be used as prognostic and predictive biomarkers of cancer.

Disulfiram combined with copper inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma through the NF-κB and TGF-ß pathways.

Late-stage hepatocellular carcinoma (HCC) usually has a low survival rate because of the high risk of metastases and the lack of an effective cure. Disulfiram (DSF) has copper (Cu)-dependent anticancer properties in vitro and in vivo. The present work aims to explore the anti-metastasis effects and molecular mechanisms of DSF/Cu on HCC cells both in vitro and in vivo. The results showed that DSF inhibited the proliferation, migration and invasion of HCC cells. Cu improved the anti-metastatic activity of DSF, while Cu alone had no effect. Furthermore, DSF/Cu inhibited both NF-κB and TGF-ß signalling, including the nuclear translocation of NF-κB subunits and the expression of Smad4, leading to down-regulation of Snail and Slug, which contributed to phenotype epithelial-mesenchymal transition (EMT). Finally, DSF/Cu inhibited the lung metastasis of Hep3B cells not only in a subcutaneous tumour model but also in an orthotopic liver metastasis assay. These results indicated that DSF/Cu suppressed the metastasis and EMT of hepatic carcinoma through NF-κB and TGF-ß signalling. Our study indicates the potential of DSF/Cu for therapeutic use.

Effectiveness and safety of endoscopic resection for gastric GISTs: a systematic review.

AIMS: To evaluate the effectiveness and safety of endoscopic resection for gastric gastrointestinal stromal tumors (GISTs). MATERIAL AND METHODS: The effectiveness and safety of endoscopic resection were mainly assessed by complete resection rate, postoperative adverse event rate, and recurrence rate. Moreover, a comparison of endoscopic with laparoscopic resection for gastric GISTs was made through weighted mean difference by STATA 12.0 with regard to operation time, blood loss, and length of stay after including patients who underwent endoscopic or laparoscopic resection for gastric GISTs in the comparative studies. RESULTS: Eleven studies investigating endoscopic resection for GISTs were included. For stromal tumors <2 cm in average diameters the pooled rates of complete resection, postoperative adverse events and recurrence were 0.97, 0.08, and 0.03, respectively. Only five retrospective studies directly compared endoscopic with laparoscopic resection for gastric GISTs with average diameters from 1.1 cm to 3.8 cm, and endoscopic resection had a shorter operation time than laparoscopic resection, but there were no significant differences in intraoperative blood loss, length of stay, postoperative complications, and postoperative recurrence rates between the two approaches. CONCLUSIONS: Endoscopic resection is predominantly tried for gastric GISTs of relatively small size. It seems effective and safe for gastric GISTs <2 cm in average diameter, with relatively short operation times.

Targeting ALDH2 with disulfiram/copper reverses the resistance of cancer cells to microtubule inhibitors.

Disulfiram (DSF) in combination with copper (Cu) has been reported to override drug resistance in cancer cells, and DSF combined with chemotherapy based on the microtubule inhibitor vinorelbine appears to prolong survival in non-small cell lung cancer patients. Here, we investigated the mechanisms underlying these findings. DSF/Cu reversed the microtubule inhibitor resistance in A549/Taxol and KB/VCR cells in vitro, and had anti-tumor effects in A549/Taxol and KB/VCR xenograft mice. DSF/Cu and DSF reduced the cancer stem cell (CSC) characteristics of drug-resistant A549/Taxol and KB/VCR cells, including sphere formation, colony generation and migration, and DSF/Cu was more effective than DSF alone. DSF/Cu also decreased the aldehyde dehydrogenase (ALDH) activity and the expression of P-gp and stem cell transcription factors in A549/Taxol and KB/VCR cells. Knockdown of ALDH2 attenuated the CSC characteristics of resistant cancer cells and enhanced their sensitivity to Taxol or VCR. Importantly, DSF/Cu treatment inhibited the expression of ALDH2 in vitro and in vivo. Our findings suggest that DSF/Cu reverses microtubule inhibitor resistance in cancer cells by suppressing ALDH2 expression, and Cu improves the activity of DSF.

A modified endoscopic method for resection of gastric submucosal tumor.

BACKGROUND AND OBJECTIVE: Endoscopic mucosa-sparing lateral dissection (EMSLD) was developed by our group, and is used to remove gastric submucosal tumor (SMT). This study aims to evaluate the feasibility and safety of this method. METHODS: This retrospective study included 25 patients who underwent EMSLDs at an endoscopy center as a national key unit in china from October 2015 to July 2016. The main data collected were the size of the gastric SMT, its location and origin, en bloc resection rate, operating time, intraoperative and postoperative complications, hospitalization expense, hospital days, and follow-up after hospital discharge. RESULTS: The mean (SD) size of the gastric SMTs was 18.3 (5.9) mm; 96% (24/25) of the tumors originated in the muscularis propria; and 64% (16/25) and 28% (7/25) were located in the gastric fundus and gastric body, respectively. The rate of en bloc resection was 96% (24/25), and the rate of intraoperative perforations due to endoscopic full-thickness resection was 48% (12/25). All wounds and perforations were effectively closed using endoscopic clips combined with the retained mucosa. The mean operative time was 74.2 (38.0) min. Delayed bleeding and perforation were not observed. CONCLUSION: Endoscopic mucosa-sparing lateral dissection is safe and feasible for the removal of gastric SMTs. The wound can be effectively closed using the retained mucosa and endoscopic clips, even if perforation has occurred. EMSLD provides an alternative to the resection of gastric SMTs, especially for tumors with a risk of intraoperative perforation.

Oligomer procyanidins (F2) repress HIF-1α expression in human U87 glioma cells by inhibiting the EGFR/ AKT/mTOR and MAPK/ERK1/2 signaling pathways in vitro and in vivo.

Hypoxia-inducible factor-1 (HIF-1) is over-expressed in gliomas and has become one of the most compelling tumor targets. In this study, we found that oligomer procyanidins (F2) can suppress the expressions of HIF-1α and its target genes in U87 cells, and also down-regulate the EGFR/PI3K/AKT/mTOR and MAPK/ERK1/2 pathways in vitro and in vivo. Furthermore, hypoxia-induced formation of tubular structures by human umbilical vascular endothelial cells and the migration and invasion of U87 cells could be inhibited by F2 in a HIF-1 dependent manner. Moreover, in a U87 xenograft tumor model, F2 significantly reduced intra-tumor vessel density and cell proliferation and finally retarded tumor growth, indicating that F2 may be a potential HIF-1 inhibitor and serve as one of candidates for glioma therapy.