Study on the Influence of Calcination Temperature of Iron Vitriol on the Coloration of Ancient Chinese Traditional Iron Red Overglaze Color.

Iron red, a traditional Jingdezhen overglaze color, is primarily colored with iron oxide (Fe2O3). In traditional processes, the main ingredient for the iron red overglaze color, raw iron red, is produced by calcining iron vitriol (FeSO4·7H2O). Analysis of ancient iron red porcelain samples indicates that the coloration is unstable, ranging from bright red to dark red and occasionally to black. Addressing this, the present study, from a ceramic technology standpoint, conducts a series of calcination experiments on industrial iron vitriol at varying temperatures. Utilizing methodologies such as differential scanning calorimetry-thermogravimetry (DSC-TG), Raman spectroscopy, X-ray diffraction (XRD), scanning electron microscopy with X-ray energy dispersive spectrometry (SEM-EDS), and optical microscopy (OM), this research scientifically explores the impact of iron vitriol's calcination temperature on the coloration of traditional Jingdezhen iron red overglaze color. The findings indicate that from room temperature to 550 °C, the dehydration of iron vitriol resulted in the formation of Fe2(SO4)3 and a minimal amount of α-Fe2O3, rendering the iron red overglaze color a yellowish-red shade. At 650 °C, the coexistence of Fe2(SO4)3 and α-Fe2O3 imparted a brick-red color to the iron red. As the temperature was elevated to 700 °C, the desulfurization of Fe2(SO4)3 produced α-Fe2O3, transitioning the iron red to an orange red. With further temperature increase to 750 °C, the particle size of α-Fe2O3 grew and the crystal reflectivity decreased, resulting in a purplish-red hue. Throughout this stage, the powder remained in a single α-Fe2O3 phase. Upon further heating to 800 °C, the crystallinity of α-Fe2O3 enhanced, giving the iron red overglaze color a dark red or even black appearance.

The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression.

BACKGROUND: Anti-PD1/PD-L1 antibody plus human epidermal growth factor receptor 2 (HER2) antibody and chemotherapy have become the new first-line therapy for HER2 overexpression-positive advanced gastric cancers (GC), suggesting that HER2 and PD-L1 play a vital role in guiding systemic treatment for patients with GC. This study aimed to depict the genomic and immune landscapes of Chinese patients with GC and investigate their correlations with HER2 amplification and PD-L1 expression. PATIENTS AND METHODS: Next-generation targeted sequencing and PD-L1 immunohistochemistry were performed on tumor samples from 735 patients with pathologically diagnosed GC. The genomic and immune landscapes and their correlations with HER2 amplification and PD-L1 expression were analyzed. RESULTS: The most commonly mutated genes in Chinese GC were TP53 (64%), CDH1 (20%), ARID1A (18%), HMCN1 (15%), KMT2D (11%), and PIK3CA (11%). Seventy-six (10%) patients were HER2 amplification, and 291 (40%) had positive PD-L1 expression. Classifying the total population based on HER2 amplification and PD-L1 expression level, 735 patients were divided into four subgroups: HER2+/PD-L1+ (4.5%), HER2+/PD-L1- (5.9%), HER2-/PD-L1+ (35.1%), and HER2-/PD-L1- (54.5%). The HER2+/PD-L1- and HER2+/PD-L1+ subgroups exhibited dramatically higher rate of TP53 mutations, CCNE1 and VEGF amplifications. The HER2+/PD-L1- subgroup also had a markedly higher rate of MYC amplification and KRAS mutations. The HER2-/PD-L1+ subgroup had significantly higher rate of PIK3CA mutations. HER2+/PD-L1- subgroup had the highest TMB level and HER2-/PD-L1+ subgroup had the highest proportion of patients with microsatellite instability-high than other subgroups. Furthermore, we observed that different HER2 amplification levels had distinct impacts on the correlations between PD-L1 expression and therapeutic genomic alterations, but no impact on the prognosis. CONCLUSION: The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.

Cancer-associated fibroblast-derived exosome miR-181b-3p promotes the occurrence and development of colorectal cancer by regulating SNX2 expression.

Tumor microenvironment (TME) (e.g., stromal cells) has been closely related to the pathological process of colorectal cancer (CRC). In TME, tumor-associated fibroblasts (CAFs) are the main stromal cells. The studies have showed that CAFs promoted tumor growth and metastasis in CRC and led to poor prognosis. Mounting evidence indicates that CAFs-mediated exosomes regulate the pathological process of neighboring tumor cells through the transmission of miRNAs. In our study, we aimed to explore the function of CAFs-derived exosome miR-181b-3p in CRC. First, the expression of miR-181b-3p in CRC was found to be up-regulated and its expression was dramatically up-regulated in CRC cells after co-incubation of CAFs-mediated exosomes with CRC cells. Then, it was found that the CAFs-derived exosomes were markedly enhanced the proliferation and migration of the CRC cells, and substantially reduced apoptosis. To elucidate the influence of CAFs-derived exosome miR-181b-3p on CRC, we overexpressed and knocked down the miR-181b-3p expression in CAFs, respectively. It was found that miR-181b-3p significantly increased the proliferation and migration of CRC cells. Furthermore, we conducted in vivo experiments. Finally, we demonstrated that CAF-derived exosome miR-181b-3p regulated sorting nexin 2 (SNX2) expression in CRC cells by bioinformatics prediction combined with luciferase reporter assay. Further cellular and animal experiments jointly elucidated that miR-181b-3p promoted the pathological process of CRC by SNX2 expression. In brief, our results demonstrated that CAFs-derived exosome miR-181b-3p promoted the pathogenesis of CRC by regulating SNX2 expression, which provides a novel idea for CRC treatment.

Cancer stem cell-like cells-derived exosomal lncRNA CDKN2B-AS1 promotes biological characteristics in thyroid cancer via miR-122-5p/P4HA1 axis.

Introduction: Here, the discussion focused on the function and possible mechanism of cancer stem cell-like cells (CSCs)-derived exosomal CDKN2B-AS1 in thyroid cancer. Methods: Specifically, the bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were conducted to obtain the expression and regulation of CDKN2B-AS1, and the downstream miR-122-5p/P4HA1 axis. Exosomes were identified by transmission electron microscopy. The uptake of exosome by recipient cells was observed by PKH67 labeling. Functional experiments and western blot were adopted to detect the effects of exosomal CDKN2B-AS1/miR-122-5p/P4HA1 axis on thyroid cancer cells. Tumor xenograft and in vivo metastasis model combined with RT-qPCR, western blot and hematoxylin-eosin staining verified the role of CDKN2B-AS1. Results: Exosomal CDKN2B-AS1 up-regulated P4HA1 expression through miR-122-5p. CDKN2B-AS1 and P4HA1 expressions were up-regulated, and miR-122-5p expression was down-regulated in thyroid cancer. Silent CDKN2B-AS1 reduced cell viability and stemness. CDKN2B-AS1 was found to be abundant in CSCs and CSCs-derived exosomes. Exosomal CDKN2B-AS1 silencing could transfer to thyroid cancer cells to elevate E-cadherin level, and diminish P4HA1, N-cadherin and Vimentin levels, thus impeding cell migration and invasion. MiR-122-5p inhibitor reversed the function of exosomal CDKN2B-AS1, while P4HA1 silencing attenuated the effect of miR-122-5p inhibitor. Exosomal CDKN2B-AS1 affected the growth and metastasis of thyroid cancer through the miR-122-5p/P4HA1 axis. Conclusion: CSCs-derived exosomal CDKN2B-AS1 acts as an oncogene in thyroid cancer through miR-122-5p/P4HA1 axis.

Oncologic outcomes of single-incision laparoscopic surgery versus conventional laparoscopic surgery for colorectal cancer (CSILS): study protocol for a multicentre, prospective, open-label, noninferiority, randomized controlled trial.

BACKGROUND: In most previous studies, single-incision laparoscopic surgery (SILS) for colorectal cancer (CRC) was feasible and safe in the short term. However, long-term oncologic outcomes remain uncertain, as only a few studies contained long-term survival data. SILS for CRC is still in the early stages of research. Further studies, particularly large-scale, prospective randomized controlled trials, are necessary to assess the value of SILS for CRC. METHODS: This study is a prospective, multicentre, open-label, noninferiority, parallel-group randomized controlled trial that investigates the long-term oncologic outcomes of SILS compared to conventional laparoscopic surgery (CLS) for CRC. A total of 710 eligible patients will be randomly assigned to the SILS group or the CLS group at a 1:1 ratio using a central, dynamic, and stratified block randomization method. Patients with ages ranging from 18 to 85 years old, of both sexes, with CRC above the peritoneal reflection diagnosed as cT1-4aN0-2M0 and a tumour size no larger than 5 cm will be considered for the study. The primary endpoint is 3-year disease-free survival (DFS). The secondary endpoints include: intraoperative outcomes, postoperative recovery, postoperative pain assessment, pathological outcomes, early morbidity and mortality rate, cosmetic effects, quality of life, 3-year overall survival (OS), incidence of incisional hernia, 5-year DFS and 5-year OS. The first two follow-up visits will be scheduled at one month and three months postoperatively, then every three months for the first two years and every six months for the next three years. DISCUSSION: Currently, no randomized controlled trials (RCTs) have been designed to investigate the long-term oncologic outcomes of SILS for CRC. This study is expected to provide clinical evidence of the oncologic outcomes of SILS compared to CLS for CRC to promote its widespread use. TRIAL REGISTRATION: ClinicalTrials.gov:  NCT04527861 (registered on August 27, 2020).

Cancer stem cell-like cells-derived exosomal CDKN2B-AS1 stabilizes CDKN2B to promote the growth and metastasis of thyroid cancer via TGF-ß1/Smad2/3 signaling.

As CDKN2B-AS1 is demonstrated to exert promotive effects on thyroid cancer (TC), this research aims to investigate the role of cancer stem cell-like cells (CSCs)-derived exosomal CDKN2B-AS1 in TC and the underlying regulatory mechanism. Specifically, CDKN2B expression and the correlation of CDKN2B with CDKN2B-AS1 in TC were determined via bioinformatics analysis and further verified by qRT-PCR. After transfection or co-culture with CSCs-derived exosomes, viability, migration, and invasion of TPC-1 and SW579 cells were evaluated by CCK-8, wound healing, and transwell assays, respectively. The uptake of exosomes by TC cells was detected by PKH67 labeling. In vivo tumor formation and metastasis models were established. Tumor volume and weight were calculated. Metastasis loci in lung tissues were observed by hematoxylin-eosin staining. The expression levels of CDKN2B-AS1, CDKN2B, and epithelial-mesenchymal transition- and TGF-ß1/Smad2/3 signaling-related factors were detected by qRT-PCR or Western blot. Concretely, CDKN2B and CDKN2B-AS1 were highly expressed in TC, and there was a positive correlation between the two. In addition, CDKN2B-AS1 promoted the translation and stability of CDKN2B. Furthermore, CDKN2B-AS1 was highly expressed in CSCs and CSCs-derived exosomes which could be absorbed by TC cells. CDKN2B silencing inhibited viability, migration, invasion, protein levels of CDKN2B, N-cadherin and Vimentin, and TGF-ß1/Smad2/3 signaling, while promoting E-cadherin expression in TC cells. CSCs-derived exosomal CDKN2B-AS1 did oppositely and reversed the effects of CDKN2B silencing on TC cells. CDKN2B silencing impeded tumor growth and metastasis in TC mice, while TGF-ß1 performed inversely and impaired the effects of CDKN2B silencing. Collectively, CSCs-derived exosomal CDKN2B-AS1 stabilizes CDKN2B to promote growth and metastasis of TC via TGF-ß1/Smad2/3 signaling.

AFF4 Predicts the Prognosis of Colorectal Cancer Patients and Suppresses Colorectal Cancer Metastasis via Promoting CDH1 Expression.

INTRODUCTION: AF4/FMR2 family member 4 (AFF4) is a core component of super elongation complex (SEC) and regulates the transcription elongation of many genes. AFF4 depletion or amplification is associated with multiple cancers, but its role in colorectal cancer (CRC) has not been investigated so far. METHODS: qRT-PCR and Western blot analyzed AFF4 expression in the paired clinical CRC tissues. The patients' overall survival curve was determined using the Kaplan-Meier plotter. In vitro experiments, such as cell proliferation, migration, and invasion, were used to preliminarily ascertain the role of AFF4 in CRC. A CRC cell liver metastasis animal model was well established. Livers were harvested and examined histologically by a series of indicators, such as tumor nodules, liver weight, ALT/AST activity, and tumor cell identification by hematoxylin-eosin (HE) staining. RESULTS: We firstly examined the expression of AFF4 in colorectal cancer and normal tissues by collecting paired CRC tissues and adjacent normal tissues, revealing that AFF4 was significantly downregulated in CRC patients and lower expression of AFF4 was correlated with poor prognosis. Next, we observed that presence or absence of AFF4 in CRC cells had no effect on cancer cell proliferation, while AFF4 depletion significantly promoted the migration or invasion of CRC cells in vitro. Furthermore, we confirmed that AFF4 deficiency enhanced the metastatic capacity of CRC cells in vivo. Mechanistically, we found that AFF4 upregulated the transcription of CDH1 gene, which encodes E-cadherin and suppresses the epithelial-mesenchymal transition (EMT). Knockdown of AFF4 interfered with CDH1 transcription, resulting in downregulation of E-cadherin expression and the progression of CRC. Moreover, restored CDH1 expression could rescue the phenotype of CRC cells without AFF4. CONCLUSIONS: Collectively, our data demonstrated that AFF4 served as a significant novel regulator of CRC via CDH1 transcriptional regulation and a potential effective therapy target for patients with CRC.

Short-Term Outcomes of Single-Incision Laparoscopic Surgery for Colorectal Cancer: A Single-Center, Open-Label, Non-Inferiority, Randomized Clinical Trial.

OBJECTIVE: To date, well-designed randomized controlled trials examining the safety, efficacy, and long-term outcomes of single-incision laparoscopic surgery (SILS) for colorectal cancer are scarce. The aim of the current study was to compare short-term outcomes of SILS for colorectal cancer with conventional laparoscopic surgery (CLS). METHODS: Between June 28, 2017, and June 29, 2019, a single-center, open-label, non-inferiority, randomized clinical trial was conducted at the Department of General Surgery, Ruijin Hospital (North), Shanghai Jiaotong University School of Medicine in Shanghai, China. In total, 200 patients diagnosed or suspected of colorectal cancer (cT1-4aN0-2M0) were randomly assigned to either the SILS or CLS group in a 1:1 ratio. The primary outcome was early morbidity rate. Secondary outcomes included intraoperative outcomes, pain intensity, postoperative recovery, pathologic outcomes, and long-term outcomes. RESULTS: In total, 193 participants (SILS, 97; CLS, 96) were analyzed in the modified intention-to-treat (MITT) population. Among them, 48 underwent right hemicolectomy (SILS n = 23, 23.7% and MLS n = 25, 26%), 15 underwent left hemicolectomy (SILS n = 6, 6.2% and MLS n = 9, 9.4%), 1 underwent transverse colectomy (MLS n = 1, 1%), 57 underwent sigmoidectomy (SILS n = 32, 33% and MLS n = 25, 26%), and 72 underwent anterior resection (SILS n = 36, 37.1% and MLS n = 36, 37.5%). No significant differences were observed in the baseline characteristics. The intraoperative complication was comparable between the two groups [5 (5.2%) vs. 4 (4.2%); difference, 1%; 95% CI, -5.8% to 7.8%; p > 0.999) and so was postoperative complication rates [10 (10.3%) vs. 14 (14.6%); difference, -4.3%; 95% CI, -13.9% to 5.3%; p = 0.392]. The SILS group showed shorter incision length [median (IQR), 4 (3.5-5) vs. 6.6 (6-7.5), p < 0.001] and lower VAS scores on the first [median (IQR), 4 (3-5) vs. 4 (4-5), p = 0.002] and the second day [median (IQR), 2 (1.5-3) vs. 3 (2-4), p < 0.001] after surgery. No statistically significant difference was found in other measured outcomes. CONCLUSIONS: Compared with CLS, SILS performed by experienced surgeons for selected colorectal cancer patients is non-inferior with good short-term safety and has the advantage of reducing postoperative pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03151733.

Pure transvaginal natural orifice transluminal endoscopic surgery right hemicolectomy for colon cancer: A case report.

BACKGROUND: Pure natural orifice transluminal endoscopic surgery (NOTES) for colorectal cancer is a complex procedure and rarely used in clinical practice because of the ethical concerns and technical challenges, including loss of triangulation, in-line orientation, and instrument collision. Transvaginal (v) NOTES, however, can overcome these technical challenges. We report a case of pure vNOTES right hemicolectomy for colon cancer, attached with surgical video. CASE SUMMARY: A 65-year-old woman with a 2-year history of intermittent diarrhea was diagnosed with ascending colon adenocarcinoma by colonoscopy and biopsy. Pure vNOTES right hemicolectomy was performed with complete mesocolic excision by well-experienced surgeons. The operative time was 200 min and the estimated blood loss was 30 mL. No intraoperative or postoperative complications occurred within 30 d after the surgery. The visual analog scale pain score on postoperative day 1 was 1 and dropped to 0 on postoperative days 2 and 3. The patient was discharged at postoperative day 6. The pathologic specimen had sufficient clear resection margins and 14 negative harvested lymph nodes. CONCLUSION: vNOTES right hemicolectomy, performed by well-experienced surgeons, overcomes the technical challenges of pure NOTES and may be feasible for colon cancer.

Comparative Effectiveness of Enhanced Recovery After Surgery Program Combined With Single-Incision Laparoscopic Surgery in Colorectal Cancer Surgery: A Retrospective Analysis.

BACKGROUND: Recently, enhanced recovery after surgery (ERAS) has been widely used in the perioperative management of colorectal cancer (CRC). This study aimed to evaluate the safety and feasibility of ERAS combined with single-incision laparoscopic surgery (SILS) in CRC surgery. METHODS: This was a retrospective study of patients with CRC who underwent surgery between April 2018 and April 2020 in Ruijin Hospital(North), Shanghai Jiaotong University School of Medicine. The patients were divided into three groups: group A (n=138), patients who underwent traditional multiport laparoscopic colectomy with conventional perioperative management; group B (n=63), patients who underwent SILS; and group C (n=51), patients who underwent SILS with ERAS. RESULTS: Overall, 252 participants were included in the retrospective study. The median operation time (min) in group B and group C was shorter than that in group A (group A 134.0 ± 42.5; group B 117 ± 38.9; group C 111.7 ± 35.4, p=0.004). The estimated surgical blood loss (ml) was lower in groups B and C than in group A (group A 165.1 ± 142.2; group B 122.0 ± 79.4; group C 105.2 ± 55.8, p=0.011). The length of surgical incision (cm) was shorter in groups B and C than in group A (group A 7.34 ± 1.05; group B 5.60 ± 0.80; group C 5.28 ± 0.52, p<0.001). The time before first flatus (hours) in group C was shorter than in groups A and B (group A 61.85 ± 21.14; group B 58.30 ± 20.08; group C 42.06 ± 23.72; p<0.001). The days prior to the administration of free oral fluids in group C was shorter than in groups A and B (group A 4.79 ± 1.28; group B 4.67 ± 1.11; group C 2.62 ± 0.64; p<0.001). The days of prior solid diet was less in group C than in groups A and B (group A 7.22 ± 3.87; group B 7.08 ± 3.18; group C 5.75 ± 1.70; p=0.027). The postoperative length of stay (LOS) was less in group C compared with that in groups A and B (group A 9.46 ± 4.84 days; group B 9.52 ± 7.45 days; group C 7.20 ± 2.37 days; p=0.023). The visual analog scale (VAS) scores on day 0, 1, and 2 in groups B and C were lower than those in group A (day 0, p<0.001; day 1, p<0.001; day 2, p=0.002), while the VAS score on day 3 showed no differences in the three groups (group A 1.29 ± 1.38; group B 0.98 ± 1.24; group C 0.75 ± 0.64, p=0.018). CONCLUSION: The findings suggest that SILS combined with ERAS may be a feasible and safe procedure for CRC surgery because it provides favorable cosmetic results, early dietary resumption, shorter hospital stays, and appropriate control of postoperative pain without increases in complications or readmission rates compared to conventional perioperative care with SILS or conventional laparoscopic surgery(CLS) of CRC. Further prospective randomized controlled studies are needed to enhance evidence-based medical evidence.

Discovering the molecular differences between right- and left-sided colon cancer using machine learning methods.

BACKGROUND: In recent years, the differences between left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have received increasing attention due to the clinicopathological variation between them. However, some of these differences have remained unclear and conflicting results have been reported. METHODS: From The Cancer Genome Atlas (TCGA), we obtained RNA sequencing data and gene mutation data on 323 and 283 colon cancer patients, respectively. Differential analysis was firstly done on gene expression data and mutation data between LCC and RCC, separately. Machine learning (ML) methods were then used to select key genes or mutations as features to construct models to classify LCC and RCC patients. Finally, we conducted correlation analysis to identify the correlations between differentially expressed genes (DEGs) and mutations using logistic regression (LR) models. RESULTS: We found distinct gene mutation and expression patterns between LCC and RCC patients and further selected the 30 most important mutations and 17 most important gene expression features using ML methods. The classification models created using these features classified LCC and RCC patients with high accuracy (areas under the curve (AUC) of 0.8 and 0.96 for mutation and gene expression data, respectively). The expression of PRAC1 and BRAF V600E mutation (rs113488022) were the most important feature for each model. Correlations of mutations and gene expression data were also identified using LR models. Among them, rs113488022 was found to have significance relevance to the expression of four genes, and thus should be focused on in further study. CONCLUSIONS: On the basis of ML methods, we found some key molecular differences between LCC and RCC, which could differentiate these two groups of patients with high accuracy. These differences might be key factors behind the variation in clinical features between LCC and RCC and thus help to improve treatment, such as determining the appropriate therapy for patients.

Correlation Research of Thymidine Synthase Expression in Circulating Tumor Cell and Clinical Characteristics of Colon Cancer.

OBJECTIVE: To explore the clinical significance of thymidine synthase (TYMS) expression in circulating tumor cells (CTC). METHODS: Patients (n=43) were recruited upon reference to the Department of Surgery at a local hospital. Arterial-portal blood samples were harvested from all patients. Patient baseline information was collected when individuals were recruited into the study and include age, sex, and tumor stage. Complete response (CR) events and progressive disease (PD) events were recorded after follow-up. The CTC positive rate and the CTC number were assessed in blood samples. Epithelial-mesenchymal transition (EMT) subgroups and related TYMS expressions were examined for their correlation with colon cancer prognosis. The TYMS expression differed among various EMT subgroups. RESULTS: In our study, the CTC number was not associated with the prognosis index of colon cancer patients. These non-associated indices also include TNM tumor stage, CEA factor, primary tumor position, pathological pattern, age, and sex. However, the total CTC positive rate was correlated with tumor stage. For patients with right colon cancer (10/35), mixed type EMT was in the majority, while epithelial type EMT was the main subgroup in patients with left colon cancer (25/35). The TYMS expression differed among various subgroups of EMT. Left colon cancer (25/35) had the negative expression level of TYMS (75%). CONCLUSIONS: CTC positive rate is a promising index for the diagnosis of colon cancer. The lack of TYMS in CTC makes EMT cells prone to becoming epithelial-like cells, and TYMS silence in CTC indicates that the tumor is in the left colon.

Exosomal miR-200c-3p negatively regulates the migraion and invasion of lipopolysaccharide (LPS)-stimulated colorectal cancer (CRC).

BACKGROUND: Colorectal cancer (CRC) is a leading cancer and a major cause of death. Lipopolysaccharide (LPS), an abundant component in gut microbiome, is involved in CRC progression and metastasis, potentially through regulating the miRNA composition of CRC-derived exosomes. In this study, we aimed to identify miRNA species in exosome which regulates CRC progression after LPS stimulation. RESULTS: Firstly, we discovered a shift of miRNA profile in CRC exosome after LPS stimulation. Among the differentially expressed miRNAs, we identified miR-200c-3p as a potential key regulator of CRC progression and metastasis. Retrospective analysis revealed that miR-200c-3p was elevated in CRC tumor tissues, but decreased in the serum exosome in CRC patients. In vitro experiments demonstrated that exosomal miR-200c-3p expression did not influence CRC cell proliferation, but negatively regulated their capacity of migration and invasion in the presence of LPS. miR-200c-3p level in exosome influenced exosomal expression of Zinc finger E-box-binding homeobox-1 (ZEB-1) mRNA, one of the miR-200c targets which affects migration and invasion capacity, and further altered ZEB-1 protein expression in CRC cell. In addition, exosomal miR-200c-3p promotes apoptosis of HCT-116 cells. CONCLUSIONS: Our findings indicate that exosomal miR-200c-3p inhibits CRC migration and invasion, and promotes their apoptosis after LPS stimulation. It is suggested as a potential diagnostic marker and therapeutic target of CRC.

Clinical and oncological outcomes of single-incision vs. conventional laparoscopic surgery for rectal cancer.

BACKGROUND: To evaluate the clinical and oncological outcomes of single-incision laparoscopic surgery (SILS) vs. conventional laparoscopic surgery (CLS) for patients with rectal cancer (RC) who underwent total mesorectal excision (TME) surgery. METHODS: This was a retrospective case-control study of patients with RC operated between 12/2013 and 12/2017 in Ruijin Hospital North, Shanghai Jiaotong University School of Medicine. In total, 177 patients who underwent CLS and 51 who underwent SILS met the inclusion and exclusion criteria and were matched 1:1 using propensity score matching method (PSM). RESULTS: Compared with the CLS group, the SILS group showed shorter operation time [105 (40) vs. 125 (55) min, P = 0.045], shorter total incision length [4 (1) vs. 6.5 (1.5) cm, P < 0.001], lower VAS score on POD2 [1 (1) vs. 2 (1), P < 0.001], shorter time to soft diet [7 (1) vs. 8 (2) days, P = 0.048], and shorter length of hospital stay [9 (2) vs. 11 (3) days, P < 0.001]. The postoperative complications were similar between two groups [1(2%) vs. 5 (9.8%), P = 0.205]. No readmissions or mortality in either group occurred within 30 days of surgery. All 102 specimens met the requirements of TME. No significant differences were observed in the pathologic outcomes between the two groups. The median follow-up period was 32.6 months in the SILS group and 36.8 months in the CLS group (P = 0.053). The 3-year disease-free survival rates and overall survival rates of the SILS and CLS groups were 89.8% vs. 96.0% (P = 0.224) and 90.9% vs. 96.9% (P = 0.146), respectively. CONCLUSIONS: Compared with CLS, TME surgery for rectal cancer can be performed safely and effectively using the SILS technique with better cosmetic results, less postoperative pain, faster postoperative recovery, and acceptable clinical and oncological outcomes.

Cell-Cycle-Dependent Phosphorylation of PRPS1 Fuels Nucleotide Synthesis and Promotes Tumorigenesis.

Nucleotide supply is essential for DNA replication in proliferating cells, including cancer cells. Ribose-phosphate diphosphokinase 1 (PRPS1) is a key enzyme to produce the consensus precursor of nucleotide synthesis. PRPS1 participates in the pentose phosphate pathway (PPP) by catalyzing the phosphoribosylation of D-ribose 5-phosphate (R-5P) to 5-phosphoribosyl-1-pyrophosphate. Therefore, PRPS1 not only controls purine biosynthesis and supplies precursors for DNA and RNA biosynthesis but also regulates PPP through a feedback loop of the PRPS1 substrate R-5P. However, it is still elusive whether PRPS1 enhances nucleotide synthesis during cell-cycle progression. In this study, we explore the role and activation mechanism of PRPS1 in cell-cycle progression of colorectal cancer, and observed a peak in its enzymatic activity during S phase. CDK1 contributes to upregulation of PRPS1 activity by phosphorylating PRPS1 at S103; loss of phosphorylation at S103 delayed the cell cycle and decreased cell proliferation. PRPS1 activity in colorectal cancer samples is higher than in adjacent tissue, and the use of an antibody that specifically detects PRPS1 phosphorylation at S103 showed consistent results in 184 colorectal cancer tissues. In conclusion, compared with upregulation of PRPS1 expression levels, increased PRPS1 activity, which is marked by S103 phosphorylation, is more important in promoting tumorigenesis and is a promising diagnostic indicator for colorectal cancer. SIGNIFICANCE: These findings show that the enzymatic activity of PRPS1 is crucial for cell-cycle regulation and suggest PRPS1 phosphorylation at S103 as a direct therapeutic target and diagnostic biomarker for colorectal cancer.

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet-derived growth factor BB.

ETS transcription factors play important roles in tumor cell invasion, differentiation and angiogenesis. In this study, we initially demonstrated that ETS translocation variant 5 (ETV5) is abnormally upregulated in colorectal cancer (CRC), is positively correlated with CRC tumor size, lymphatic metastasis and tumor node metastasis (TNM) stage and indicates shorter survival and disease-free survival in CRC patients. In vitro and in vivo experiments revealed that the downregulation of ETV5 could significantly suppress CRC cell proliferation. Moreover, overexpression of ETV5 could stimulate CRC angiogenesis in vitro and in vivo, which is consistent with RNA-seq results. Then, we identified platelet-derived growth factor BB (PDGF-BB) as a direct target of ETV5 that plays an important role in ETV5-mediated CRC angiogenesis through an angiogenesis antibody microarray. Additionally, PDGF-BB could activate VEGFA expression via the PDGFR-ß/Src/STAT3 pathway in CRC cells and appeared to be positively correlated with ETV5 in CRC tissues. Finally, we revealed that ETV5 could bind directly to the promoter region of PDGF-BB and regulate its expression through ChIP and luciferase assays. Overall, our study suggested that the transcription factor ETV5 could stimulate CRC malignancy and promote CRC angiogenesis by directly targeting PDGF-BB. These findings suggest that EVT5 may be a potential new diagnostic and prognostic marker in CRC and that targeting ETV5 might be a potential therapeutic option for inhibiting CRC angiogenesis.

Clinical and oncologic outcomes of single-incision laparoscopic surgery for right colon cancer: a propensity score matching analysis.

BACKGROUND: Single-incision laparoscopic surgery (SILS) for right colon cancer is going to be considered as a new option. The potential benefits, clinical, and oncologic outcomes are still controversial. The aim of this study was to investigate clinical and oncologic outcomes of single-incision laparoscopic surgery (SILS) compared to conventional laparoscopic surgery (CLS) for right colon cancer using propensity score matching analysis. METHODS: From December 2013 to June 2017, 174 patients underwent laparoscopic radical right hemicolectomy through a single-incision (n = 32) or a conventional (n = 142) approach. The data were prospectively collected and the patients were matched at a radio of 1:1 according to age, sex, body mass index (BMI), previous abdominal surgeries, comorbidities, ASA score (≤ 2/> 2), and pathologic stage. RESULTS: No significant differences were observed in estimated blood loss, time to diet, postoperative pain score, length of hospital stay between the SILS and CLS groups. However, the SILS group showed longer operation time (175 (40) vs 145 (52.5), p = 0.011) and shorter incision length (4 (1.4) vs 7 (1.9), p < 0.001). There were 2 (6.3%) postoperative complications in the SILS group and 5 (15.6%) in the CLS group (p = 0.426). The pathologic outcomes were similar between two groups. The median follow-up period was 26.5 months in the SILS group and 34.9 months in the CLS group (p = 0.002). There were 3 recurrences (9.4%) in the SILS group and 3 (9.4%) in the CLS group. The 3-year disease-free survival rates were 92.4 and 93.8% (p = 0.984), and overall survival rates were 92.3 and 93.0% (p = 0.884) in the SILS and the CLS groups, respectively. No incisional hernia was observed during the follow-up period. CONCLUSIONS: Though single-incision laparoscopic surgery for right colon cancer showed longer operation time in this study, it appears to be a safe and feasible option with comparable clinical and oncologic outcomes to conventional laparoscopic surgery.

[Intraoperative radiotherapy for rectal cancer].

Radiotherapy, surgery and chemotherapy are the main treatments for cancer. Though intraoperative radiotherapy(IORT) for rectal cancer is still at its preliminary stage in China, patients can get more benefits from IORT than pre- or post-operative radiotherapy. IORT improves local control for locally advanced rectal cancer and improves overall survival rate of locally recurrent rectal cancer. In general, IORT is safe and feasible. It will be widely used for patients with rectal cancer in the future.

[Progress of surgical managements in patients with local recurrent rectal cancer].

Local recurrent rectal cancer (LRRC) is located in the pelvis with or without distant metastasis. It is life-threatening for patients with rectal cancer. Despite the addition of imaging technology, preoperative neoadjuvant therapy and total mesorectal excision, loco-regional relapse still occurs with an incidence as high as 10% in recent reports. Non-operative approaches to management such as radiotherapy and chemotherapy can only prolong survival time by 1 year. Improvements in surgical techniques, reconstruction methods and management of preoperative complications have helped increase the cure rate of patients with recurrent rectal cancer. Multimodality therapy based on surgery is the key of treating LRRC. This review article highlights the progress in surgical managements for local recurrent rectal cancer.