Search

The study is aimed at investigating the effect of the FLOT2 gene on invasion and metastasis of colorectal cancer (CRC) cells and the corresponding molecular mechanism by preparing polylysine-silicon nanoparticles. Specifically, polylysine was used to modify the silica nanoparticles prepared by the emulsification method to obtain polylysine-silicon nanoparticles. The characterization of polylysine-silicon nanoparticles was completed by nanoparticle size analyzer, laser particle size potentiometer, and transmission microscope. The influence of polylysine-silicon nanoparticles on the survival rate of CRC cell line HT-29 was detected using the method of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). The FLOT2-siRNA expression vector was constructed and transfected with HT-29. The HT-29 transfected with empty plasmid was used as the negative control (NC). Western Blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect expression levels of FLOT2 gene and epithelial-mesenchymal transition- (EMT-) related genes. Transwell invasion assay, Transwell migration assay, and CCK8 assay were used to detect the cell invasion, migration, and proliferation. The results showed that the average particle size of polylysine-silicon nanoparticles was 30 nm, the potential was 19.65 mV, the particle size was 65.8 nm, and the dispersion coefficient was 0.103. At the same concentration, the toxicity of silicon nanoparticles to HT-29 was significantly lower than that of liposome reagent, and the transfection efficiency was 60%, higher than that of liposome reagent (40%). The mRNA level and protein expression of the FLOT2 gene in the FLOT2-siRNA group were significantly lower than those in the NC group ( P < 0.01 ). The optical density (OD) value of the NC group and the blank control (CK) group were significantly higher than that of FLOT2-siRNA cells ( P < 0.01 ). The OD value of FLOT2-siRNA cells was lower than that of NC cells at 48 h, 72 h, and 96 h ( P < 0.01 ). The mRNA levels and protein expressions of MMP2 and vimentin in the FLOT2-siRNA group were significantly lower than those in the NC group and CK group ( P < 0.01 ). The mRNA level and protein expression of the E-cadherin gene in the FLOT2-siRNA group were significantly higher than those in the NC group and CK group ( P < 0.01 ). In conclusion, an RNA interference plasmid with high transfection efficiency and low cytotoxicity was established based on nanotechnology. siRNA-mediated FLOT2 protein inhibits the invasion, migration, and proliferation of CRC cells by regulating the expression changes of EMT-related genes, which provides a scientific basis for clinical treatment of CRC.

Electronic skin has aroused extensive research interest due to high similarity with human skin. Realizing a multifunctional electronic skin that is highly consistent with skin functions and endowed with more other functions is now a more urgent need and important challenge. Here, we use 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-oxidized cellulose nanofibril (TOCN) dispersion and highly conductive Ti

Background Natural orifice specimen extraction surgery for colorectal cancer has been introduced in order to reduce the abdominal incision, demonstrating major development potential in minimally invasive surgery. We are conducting this randomized controlled trial to assess whether robotic NOSES is non-inferior to traditional robotic-assisted surgery for patients with colorectal cancer in terms of primary and secondary outcomes. Method/design Accordingly, a prospective, open-label, randomized controlled, parallel-group, multicenter, and non-inferiority trial will be conducted to discuss the safety and efficacy of robotic natural orifice extraction surgery compared to traditional robotic-assisted surgery. Here, 550 estimated participants will be enrolled to have 80% power to detect differences with a one-sided significance level of 0.025 in consideration of the non-inferiority margin of 10%. The primary outcome is the incidence of surgical complications, which will be classified using the Clavien-Dindo system. Discussion This trial is expected to reveal whether robotic NOSES is non-inferior to traditional robotic-assisted surgery, which is of great significance in regard to the development of robotic NOSES for patients with colorectal cancer in the minimally invasive era. Furthermore, robotic NOSES is expected to exhibit superiority to traditional robotic-assisted surgery in terms of both primary and secondary outcomes. Trial registration ClinicalTrials.govNCT04230772. Registered on January 15, 2020.

Background Studies on surgical outcomes after robotic surgery are increasing; however, long-term oncological results of studies comparing robotic-assisted distal gastrectomy (RADG) versus laparoscopic-assisted distal gastrectomy (LADG) for advanced gastric cancer (AGC) are still limited. This study aimed to assess the surgical and oncological outcomes of RADG and LADG for the treatment of AGC. Methods A total of 1164 consecutive AGC patients undergoing RADG or LADG were enrolled between January 2015 and October 2021. Propensity score-matched (PSM) analysis was performed to minimize selection bias. The perioperative and oncological outcomes between the two groups were compared. Results Patient’s characteristics were comparable between the two groups after PSM. RADG group represented a longer operative time (205.2 ± 43.1 vs 185.3 ± 42.8 min, P P P = 0.015), more retrieved LNs in the supra-pancreatic areas (13.4 ± 5.0 vs 11.4 ± 5.1, P P P = 0.242). In the subgroup analysis, the benefits of RADG were more evident in high BMI patients. Moreover, the 3-year overall survival (75.5% vs 73.1%, P = 0.471) and 3-year disease-free survival (72.9% vs 71.4%, P = 0.763) were similar between the two groups. Conclusion RADG appears to be a safe and feasible procedure and could serve as an alternative treatment for AGC in experienced centers.

Robotic rectal cancer resection with natural orifice extraction is a recently developed minimally invasive surgery used in the treatment of patients with rectal cancer. However, its safety and feasibility remain undiscussed and controversial. This study reported the clinical outcomes and prognostic factors pertaining to traditional robotic assisted rectal cancer resection alone against that of robotic rectal cancer resection with natural orifice extraction to provide a discussion on this issue. 49 patients who underwent robotic rectal cancer resection with natural orifice extraction and 49 matched patients who underwent conventional robotic assisted rectal cancer resection were systematically analyzed in this study. Regarding the baseline characteristics, after matching, no significant differences were observed between the natural orifice specimen extraction (NOSE) group and the robotic assisted rectal cancer resection (RARC) group. Patients in the NOSE group had a reduced visual analog scale (p p = 0.002) and suffered less surgical stress than those in the RARC group. Moreover, 4 complications were observed in the NOSE group and 7 complications in the RARC group with no significant difference (p = 0.337) in terms of complications. The two groups had a similar survival outcomes, where the 3-year overall survival (p = 0.738) and 3-year progression-free survival (p = 0.986) were all comparable between the two groups. Histological differentiation and T stage could be regarded as independent prognostic factors for 3-year overall survival and 3-year progression-free survival. Robotic rectal cancer resection with natural orifice extraction is a safe and feasible minimally invasive surgery for patients suffering from rectal cancer as it encompasses considerable several advantages. Histological differentiation and T stage may serve as independent prognostic factors for 3-year overall survival and 3-year progression-free survival.

Background Urogenital dysfunction is recognized as a serious complication affecting patient quality of life after rectal cancer surgery to treat rectal cancer; however, the studies focus on the urogenital function after robot-assisted rectal cancer surgery compared to laparoscopic surgery are limited. Methods Male patients undergoing robotic total mesorectal excision (R-TME) or laparoscopic total mesorectal excision (L-TME) were prospectively enrolled. The International Prostate Symptom Score (IPSS) and the five-item version of the International Index of Erectile Function (IIEF-5) scale were used to compare the urogenital function of the two groups preoperatively and 3, 6, and 12 months postoperatively. Results Eighty-nine patients who planned to undergo R-TME and L-TME were prospectively enrolled; 77 patients of these patients (86.5%) completed all questionnaires at all time points and were thus included in the final analysis. Of the included patients, 38 underwent R-TME and 39 underwent L-TME. There was no significant difference in age, BMI, American Society of Anesthesiologists (ASA) score, tumor location, neoadjuvant therapy, operation method, postoperative pathological results and adjuvant therapy between the two groups. Preoperative urogenital function was similar in both groups; however, the IPSS was significantly lower in R-TME patients than that in T-TME patients at 6 months and 12 months [(7.82 ± 2.25 vs. 9.95 ± 3.01, P = 0.006; 7.62 ± 2.5 vs. 9.12 ± 2.64, P = 0.012)]. IIEF-5 scores decreased 3 months after R-TME and L-TME surgery (14.87 ± 3.27 vs. 13.92 ± 3.62, p = 0.231) and then gradually increased; at 12 months, IIEF-5 scores were comparable to those at baseline in both groups. IIEF-5 scores were higher in R-TME patients than those in L-TME patients at 6 months (18.55 ± 3.45 vs. 16.75 ± 3.26, P = 0.021), but there was no significant difference between the two groups at 12 months (21.22 ± 3.06 vs. 19.95 ± 3.03, P = 0.071). Conclusions The robotic approach for TME was associated with more rapid restoration of male urogenital function than the laparoscopic approach.

Purpose By comparing short- and long-term outcomes following totally robotic radical distal gastrectomy (TRDG) and robotic-assisted radical distal gastrectomy (RADG), we aimed to assess in which modus operandi patients will benefit more. Methods From January 2015 to May 2019, we included 332 patients undergone RADG (237) and TRDG (95). Based on the propensity score matching (PSM), inclusion and exclusion criteria, 246 patients were finally included in the propensity score-matched cohort including RADG group (164) and TRDG group (82). We then compared the short- and long-term outcomes following both groups. Results Propensity score-matched cohort revealed no significant differences in both groups. Intra-abdominal bleeding, time to pass flatus, postoperative activity time, length of incision hospital stays, and stress response were significantly less in TRDG group than in RADG group. We observed 30 complications in RADG group while 13 complications in TRDG group. There were no significant differences in TRDG group and RADG group in terms of operation time, time for anastomosis, proximal resection, distal resection margin, number of lymph node resection, and total hospitalization cost. Both 3-year overall survival and 3-year disease-free survival were comparable in both groups. Conclusions TRDG is a safe and feasible modus operandi profiting from short- and long-term outcomes compared with RADG. As surgeons improving their professional skills, TRDG could serve as the standard procedure for distal locally advanced gastric cancer with D2 lymphadenectomy.

Stress-induced intracellular proteome aggregation is a hallmark and a biomarker of various human diseases. Current sensors requiring either cellular fixation or covalent modification of the entire proteome are not suitable for live-cell applications and dynamics study. Herein, we report a noncovalent, cell-permeable, and fluorogenic sensor that can reversibly bind to proteome amorphous aggregates and monitor their formation, transition, and clearance in live cells. This sensor was structurally optimized from previously reported fluorescent protein chromophores to enable noncovalent and reversible binding to aggregated proteins. Unlike all previous sensors, the noncovalent and reversible nature of this probe allows for dynamic detection of both the formation and clearance of aggregated proteome in one live-cell sample. Under different cellular stresses, this sensor reveals drastic differences in the morphology and location of aggregated proteome. Furthermore, we have shown that this sensor can detect the transition from proteome liquid-to-liquid phase separation to liquid-to-solid phase separation in a two-color imaging experiment. Overall, the sensor reported here can serve as a facile tool to screen therapeutic drugs and identify cellular pathways that ameliorate pathogenic proteome aggregation in live-cell models.

MicroRNA (miR)‑744‑5p serves a pivotal role in the progression of multiple cancers; however, the function of miR‑744‑5p in colorectal cancer (CRC) remains largely unknown. In the present study, the effects of miR‑744‑5p on the progression of CRC were analyzed and the mechanisms involved were investigated. It was revealed that miR‑744‑5p was frequently downregulated in CRC tissues and cell lines. Overexpression of miR‑744‑5p significantly inhibited the proliferation, colony formation, and promoted the apoptosis of CRC cells. Bioinformatics analysis revealed that Septin 2 (SEPT2) was a potential target of miR‑744‑5p. miR‑744‑5p bound the 3'‑untranslated region (UTR) of SEPT2 and reduced the level of SEPT2 in CRC cells. A negative correlation between the expression of miR‑744‑5p and SEPT2 was observed in CRC tissues. Overexpression of SEPT2 counteracted the suppressive effect of miR‑744‑5p on the proliferation and apoptosis of CRC cells. Collectively, these data demonstrated the functional mechanism of miR‑744‑5p by targeting SEPT2, which suggested miR‑744‑5p as a potential target for the treatment of patients with CRC.

Gastric cancer is the most commonly occurring cancer with a rapidly increasing incidence rate worldwide. The underlying molecular mechanisms of gastric cancer require further investigation. MicroRNAs exhibit tissue sensitivity as tumor biomarkers that play a role by promoting tumor growth as oncogenes or tumor suppressor genes. We evaluated the effects of microRNA-12129 on gastric cancer and identified the underlying mechanisms of microRNA-12129. Quantitative real-time polymerase chain reaction was conducted to determine the expression levels of microRNA-12129 and sirtuin 1 in vivo and in vitro, and Western blot analysis was performed to detect sirtuin 1 at the protein level in gastric cancer cell lines. Cell proliferation and cell cycle progression were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. The potential targets of microRNA-12129 were predicted by bioinformatics analysis. The targets of microRNA-12129 were confirmed by luciferase reporter assay and rescue assay. We found that microRNA-12129 was downregulated in gastric cancer tissues and gastric cancer cell lines and was significantly associated with the prognosis of patients with gastric cancer. In addition, microRNA-12129 overexpression suppressed tumor cell proliferation and blocked cell cycle progression. Bioinformatics analysis and luciferase reporter assay suggested that sirtuin 1 was a target of microRNA-12129, and sirtuin 1 expression was negatively related to microRNA-12129. Restoration of sirtuin 1 partly reduced the inhibition of cell proliferation and cell cycle progression induced by microRNA-144. Our results collectively suggested that microRNA-12129 suppressed cell proliferation and cell cycle progression in gastric cancer by targeting sirtuin 1. These findings indicated that manipulation of microRNA-12129 expression could help develop a novel therapeutic strategy for gastric cancer.

Reports in the field of robotic surgery for gastric cancer are increasing. However, studies only on patients with advanced gastric cancer (AGC) are lacking. This retrospective study was to compare the short-term outcomes of robotic-assisted distal gastrectomy (RADG) and laparoscopic-assisted distal gastrectomy (LADG) with D2 lymphadenectomy for AGC. From December 2014 to November 2019, 683 consecutive patients with AGC underwent mini-invasive assisted distal gastrectomy. Propensity-score matching (PSM) analysis was conducted to reduce patient selection bias. Short-term outcomes were compared between the two groups. The clinical features were well matched in the PSM cohort. Compared with the LADG group, the RADG group was associated with less operative blood loss, a lower rate of postoperative blood transfusion, less volume of abdominal drainage, less time to remove abdominal drainage tube, retrieved more lymph node, and lower rates of surgical complications and pancreatic fistula (P P > 0.05). This study suggests that RADG is a safe and feasible technique with better short-term outcomes than LADG for AGC.

Previous studies have shown that Rho guanine nucleotide exchange factor 7 (ARHGEF7) is implicated in cytoskeleton remodelling, which is important for cell motility and invasiveness, and exhibits frequent high-level genetic amplification in metastatic lesions of colorectal adenocarcinoma. Therefore, it was hypothesized that ARHGEF7 may be involved in the metastasis of colorectal adenocarcinoma. In the present study, it was demonstrated that the expression level of ARHGEF7 was significantly upregulated in colorectal adenocarcinoma tumor tissues compared with matched nontumorous tissues, and its expression level correlated with colorectal adenocarcinoma metastasis. In vitro assays showed that the overexpression of ARHGEF7 in CRC cells significantly enhanced cell migration and invasion, whereas the knockdown of ARHGEF7 in colorectal adenocarcinoma cells significantly decreased cell migration and invasion. In vivo assays showed that the overexpression of ARHGEF7 in CRC cells facilitated tumor metastasis, whereas the knockdown of ARHGEF7 in CRC cells significantly inhibited tumor metastasis. Furthermore, it was demonstrated that ARHGEF7 promoted cell motility by regulating the actin cytoskeleton. Finally, according to ReMARK guidelines for reporting prognostic biomarkers in cancer, it was found that a high expression of ARHGEF7 was significantly correlated with lymph node, mesenteric and distant metastasis. Patients with colorectal adenocarcinoma with a high expression of ARHGEF7 had shorter disease-free survival (DFS) and shorter overall survival (OS) rates, compared with those with a low expression of ARHGEF7, as determined by the Kaplan-Meier method with a log-rank test. Cox regression analysis showed that a high expression of ARHGEF7 was an independent risk factor for DFS and OS rates in colorectal adenocarcinoma.

Colorectal cancer (CRC) is among the cancers with the highest incidence globally, and it currently ranks as the fourth leading cause of cancer-related deaths worldwide. Novel strategies for the treatment of advanced CRC are urgently needed, and adoptive transfer of allogeneic natural killer (NK) cells represents an attractive option. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound interleukin (IL)-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of interferon-γ, tumor necrosis factor-α, granulocyte-macrophage colony stimulating factor, and chemokine ligand 3 compared with IL-2-stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. Higher numbers of NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Bevacizumab increased extravasation of adoptively transferred NK cells into LoVo tumors and improved the therapeutic activity of eUCB-NK cells. These results justify clinical translation of UCB-derived NK cell-based therapeutics, used alone or in combination with bevacizumab, as a novel treatment option for patients with CRC.

Supplemental Digital Content is available in the text, Rationale: Synchronous double malignancies, including carcinoma of the ampulla of Vater and rectal carcinoma, are generally uncommon occurrences in the gastrointestinal tract. Patient concerns: The present study report a case of a 37-year-old man who was incidentally found to suffer from carcinoma of the ampulla of Vater and rectal carcinoma. Diagnoses: The duodenoscopy was performed and revealed an ulcerated and bulky ampulla of Vater, the biopsy from which revealed a moderate-differentiated adenocarcinoma, A local hospital colonoscopy confirmed a tumor located in rectal 7 cm from the anal margin and biopsy-confirmed poorly differentiated adenocarcinoma. Interventions: About such patient treatment, both open and laparoscopic surgery are restricted because of operation complexity, large injury, and poor cosmetic effect. surgery performed using Da Vinci robotic surgical system (DVSS). Outcomes: No evidence of recurrence or relapses was found in the first year after surgery. Lessons: Although sporadic double malignancies are uncommon, they should be considered when evaluating cancer patients. Complex surgery performed by robotic surgery may became surgeon's preferred treatment modality.

Partitioning defective 3–like protein is a novel cell polarity protein. Recently, partitioning defective 3–like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3–like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3–like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues. We found that colorectal cancer tissues had much stronger partitioning defective 3–like protein immunoreactivity than normal tissues, and colorectal cancer patients with positive partitioning defective 3–like protein expression were characterized with higher cancer stages, metastasis, poor tumor differentiation, larger tumor size, as well as high levels of colorectal cancer markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning defective 3–like protein overexpression was independently predictive of lower survival rate in colorectal cancer patients, even after adjusting the influence of cofactors. Moreover, we also found that partitioning defective 3–like protein was associated with rapid growing colorectal cancer, while knockdown of partitioning defective 3–like protein expression largely inhibited cancer cell proliferation. Our study provided the first evidence that partitioning defective 3–like protein was overexpressed in colorectal cancer and associated with disease malignancy. Also, partitioning defective 3–like protein may serve as a promising prognostic marker and a potential therapeutic target for colorectal cancer treatment. Further study is necessary to understand the regulatory mechanism of partitioning defective 3–like protein in colorectal cancer and the feasibility of its application in clinic.

Stomatin-like protein 2 (SLP-2) is a member of the highly conserved stomatin protein family whose homologues span from Archaea to humans and include stomatin, SLP-1, and SLP-3. Several studies have indicated that overexpression of SLP-2 is strongly associated with adhesion and migration in several human cancers. The aim of the present study was to evaluate SLP-2 expression at the mRNA and protein level in patients with gastric cancer (GC) and to examine the relationships between SLP-2 expression, clinicopathological features, and prognosis.We investigated SLP-2 expression in primary GC and paired normal gastric tissue by real-time PCR (RT-PCR; n = 16) and Western blot analysis (n = 32). Additionally, we performed immunohistochemistry (IHC) on 113 paraffin-embedded GC specimens, 30 matched normal specimens, and 30 paired metastatic lymph node samples.SLP-2 is overexpressed in GC compared with the adjacent normal gastric epithelium (p0.001), and high-level SLP-2 expression is significantly correlated with the depth of invasion, lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Furthermore, elevated SLP-2 expression is an independent prognostic factor in multivariate analysis using the Cox regression model (p = 0.005).Overexpression of SLP-2 may contribute to the progression and poor prognosis of GC.

Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC.

Altered expressions of nonmuscle myosin IIA (NMIIA) have been observed in certain types of cancers, but the impact of the alterations in gastric cancer (GC) remains unclear. The purpose of this study was to evaluate the expression of NMIIA at the mRNA and protein level in patients with GC and to assess its clinical significance. We investigated the expression of NMIIA in fresh, paired GC tissues by reverse transcriptase polymerase chain reaction (RT-PCR; n = 14) and Western blot analysis (n = 36). Simultaneously, we performed immunohistochemistry (IHC) on paraffin embedded specimens, including 96 GC specimens, 30 matched normal specimens and 30 paired metastatic lymph node samples. NMIIA is overexpressed in GC compared with the adjacent normal gastric epithelium (p < 0.001) and high-level NMIIA expression is significantly correlated with the depth of wall invasion, lymph node metastasis, distant metastasis and Tumor Node Metastasis (TNM) stage. Furthermore, elevated NMIIA expression is an independent prognostic factor in multivariate analysis using the Cox regression model (p = 0.021). These findings indicate that overexpression of NMIIA may contribute to the progression and poor prognosis of GC.

Colorectal cancer (CRC) patients with peritoneal carcinomatosis (PC) have a poor prognosis. Over the last decade, increasing evidence has suggested that the Collagen Triple Helix Repeat Containing 1 (CTHRC1) gene is involved in cancer progression and invasion. In this study, we investigated the expression of CTHRC1 in CRC and its potential as a prognostic factor for CRC patients with PC. Microarray analysis of four fresh paired samples showed that the expression of CTHRC1 in peritoneal metastases was higher than that in the corresponding primary tumor. These results were validated using semi-quantitative reverse transcription and polymerase chain reaction. Finally, immunohistochemical analysis showed that CTHRC1 was increased in the peritoneal metastasis group (n = 30) and the primary cancer with peritoneal metastasis group (n = 57) compared to the primary cancer without peritoneal metastasis group (n = 54), both P