Nanomaterials Enhance Pyroptosis-Based Tumor Immunotherapy.

Pyroptosis, a pro-inflammatory and lytic programmed cell death pathway, possesses great potential for antitumor immunotherapy. By releasing cellular contents and a large number of pro-inflammatory factors, tumor cell pyroptosis can promote dendritic cell maturation, increase the intratumoral infiltration of cytotoxic T cells and natural killer cells, and reduce the number of immunosuppressive cells within the tumor. However, the efficient induction of pyroptosis and prevention of damage to normal tissues or cells is an urgent concern to be addressed. Recently, a wide variety of nanoplatforms have been designed to precisely trigger pyroptosis and activate the antitumor immune responses. This review provides an update on the progress in nanotechnology for enhancing pyroptosis-based tumor immunotherapy. Nanomaterials have shown great advantages in triggering pyroptosis by delivering pyroptosis initiators to tumors, increasing oxidative stress in tumor cells, and inducing intracellular osmotic pressure changes or ion imbalances. In addition, the challenges and future perspectives in this field are proposed to advance the clinical translation of pyroptosis-inducing nanomedicines.

Adult intussusception: a challenge to laparoscopic surgery?

Background: Intussusception can occur at any age and is common in children but less common in adults. This study aimed to evaluate our experience of 51 adult intussusception and study the etiology, clinical manifestations, diagnosis, and treatment. Methods: This analysis assessed the clinical manifestations, etiology, diagnosis, and treatment of adult intussusception in 51 adult patients at the Department of Gastrointestinal Surgery of China-Japan Union Hospital of Jilin University from January 2010 to December 2020. Results: The mean age of the cohort was 54.43 ± 18.21 years, and 42 patients were diagnosed by abdominal ultrasonography and abdominal computed tomography (CT). Among them, 76.5% (39/51) had abdominal pain, 11.8% (6/51) had blood in stool, and 5.9% (3/51) had a palpable abdominal mass. Of these, 62.7% had tumors: malignant accounted for 39.2% (20/51) and benign accounted for 23.5% (12/51). CT is the preferred imaging method with a sensitivity of 92.2%, while colonoscopy provides a complementary diagnosis in patients involving the colon. All patients underwent surgical treatment, including 21.6% (11/51) laparoscopic surgery, 74.5% (38/51) open surgery, and 5.9% (3/51) intussusception reduction during the operation. The average operation time of the open group was 133.27 ± 43.75 min and the average hospital stay was 16.24 ± 12.55 days, while the average operation time of the laparoscopic group was 140.50 ± 46.15 mins, and the average hospital stay was 16.60 ± 16.98 days (P > 0.05). Conclusion: Adult intussusception is a rare disease in clinic. Laparoscopic surgery can be useful and safe for adult intussusception.

Nanomaterials Enhance the Immunomodulatory Effect of Molecular Targeted Therapy.

Molecular targeted therapy, a tumor therapy strategy that inhibits specific oncogenic targets, has been shown to modulate the immune response. In addition to directly inhibiting the proliferation and metastasis of tumor cells, molecular targeted drugs can activate the immune system through a variety of mechanisms, including by promoting tumor antigen processing and presentation, increasing intratumoral T cell infiltration, enhancing T cell activation and function, and attenuating the immunosuppressive effect of the tumor microenvironment. However, poor water solubility, insufficient accumulation at the tumor site, and nonspecific targeting of immune cells limit their application. To this end, a variety of nanomaterials have been developed to overcome these obstacles and amplify the immunomodulatory effects of molecular targeted drugs. In this review, we summarize the impact of molecular targeted drugs on the antitumor immune response according to their mechanisms, highlight the advantages of nanomaterials in enhancing the immunomodulatory effect of molecular targeted therapy, and discuss the current challenges and future prospects.

Overexpression of Long Non-Coding RNA FGF14-AS2 Inhibits Colorectal Cancer Proliferation Via the RERG/Ras/ERK Signaling by Sponging microRNA-1288-3p.

Colorectal cancer remains one of most common cancer types with poor prognosis globally. Recent years, numerous studies depicted pivotal roles of lncRNAs in colorectal cancer progression. This study aimed to investigate the role of FGF14-AS2 in colorectal cancer development. FGF14-AS2 was found as a significantly downregulated lncRNA in TCGA dataset. Via RT-qPCR, we confirmed the downregulation of FGF14-AS2 in collected colorectal carcinoma samples. Transfection of plasmid containing full length of FGF14-AS2 repressed cell proliferation and induced elevation of cell apoptosis in colorectal cancer cells. In addition, FGF14-AS2 overexpression inactivated MAPK/ERK signaling in cells. Bioinformatic analysis and subsequent cell-based assays showed that FGF14-AS2 sponging miR-1288-3p, an oncogenic miRNA in colorectal cancer. RERG, the regulator of Ras/ERK pathway, was predicted and verified as target gene of miR-1288. Via downregulation of miR-1288, FGF14-AS2 elevated RERG expression in colorectal cancer cells. Rescue assays indicated that FGF14-AS2 relied on regulation of RERG to control cell proliferation and apoptosis in colorectal cancer. Taken together, the current study demonstrated FGF14-AS2 as a regulator of colorectal cancer development via downregulation of miR-1288-3p and inactivation of Ras/ERK signaling.

Intestinal Schwannoma: A Clinicopathological, Immunohistochemical, and Prognostic Study of 9 Cases.

BACKGROUND: Intestinal schwannoma is a type of intestinal interstitial tumor with a very low incidence. At present, there are few studies on intestinal schwannoma. METHODS: From January 2010 to January 2018, the patients diagnosed with intestinal schwannoma at the China-Japan Union Hospital of Jilin University were retrospectively reviewed. The patients' clinicopathological features and prognosis were analyzed. RESULTS: This study enrolled 9 patients with intestinal schwannoma, including 3 males and 6 females. The main symptoms of the patients were abdominal pain and melena. Abdominal computed tomography showed intussusception, slightly high-density shadowing in the intestine, thickening of the intestinal wall, and an intestinal mass. Colonoscopy and endoscopic ultrasonography showed submucosal masses without ulcer formation. Two patients underwent endoscopic biopsy, and the pathological results revealed inflammation and necrosis. One patient had increased neuron-specific enolase (NSE) levels. Immunohistochemical analysis showed that the tumor cells were positive for S-100 and negative for CD117, DOG-1, desmin, and smooth muscle actin. An average of 17 lymph nodes were found around the intestines in 4 patients, all of which demonstrated reactive hyperplasia. No recurrence or metastasis occurred during postoperative follow-up. CONCLUSIONS: Intestinal schwannoma is a rare tumor, and in our study its incidence was higher in women than in men. The main symptoms were abdominal pain and melena. Preoperative increases in NSE levels might contribute to a diagnosis. Complete surgical resection with free negative margins is the standard treatment for benign schwannoma. There was no recurrence or metastasis after complete surgical resection, suggesting that follow-up may not be required.

Knockdown GREM1 suppresses cell growth, angiogenesis, and epithelial-mesenchymal transition in colon cancer.

Gremlin 1 (GREM1), as a bone morphogenetic protein (BMP) antagonist and vascular endothelial growth factor receptor-2 (VEGFR2) novel agonist, has been confirmed as overexpressed in colorectal cancer (CRC) tissues but its role in carcinogenesis remains unclear. Here we reported that the GREM1 expression in mesenchymal-like colon cancer cells (SW620 and SW480) was significantly higher than that of epithelial-like colon cancer cells (Caco-2, HTC116, and HT29) and normal colon cell. Simultaneously, we analyzed two series of CRC transcriptomes from Gene Expression Omnibus (GEO) databases and found the great majority of primary CRC tissues expressed high level of GREM1 messenger RNA (mRNA) compared with adjacent normal tissues, and that the GREM1 mRNA expression is correlated with low histological grade development and stage 2 to 3 metastatic recurrence in CRC based on a data analysis of 104 different stage CRC tissue from the GEO databases. Functional studies showed that GREM1 silencing by short hairpin RNA (shRNA) significantly inhibited CRC cells proliferation, migration, the formation of vascular endothelial growth factor (VEGF)-induced capillary structure of human umbilical vein endothelial cells (HUVECs), and epithelial-mesenchymal transition in colon cancer cells by repressing phosphorylation levels of BMP downstream signal Smad1, vascular endothelial growth factor (VEGF) downstream signal matrix metallopeptidase 2 (MMP2), and metastasis-related factor C-X-C motif chemokine ligand 12 (CXCL12) expression. In addition, shGREM1 combined with VEGF inhibitor BAW2881 displayed more effective antiangiogenesis to inhibit the tube formation of HUVEC. Hence, these experiments demonstrated that GREM1 is involved in CRC development and procession and provide a new idea for CRC diagnosis, resistance therapy, and prognosis.

Gastrointestinal hemorrhage caused by adult intussusception secondary to small intestinal tumors: Two case reports.

RATIONALE: Adult intussusception is rarely observed, and the clinical manifestations are very atypical. The most common symptom is abdominal pain, while the incidence of hematochezia is relatively low. We report two cases of adult intussusception secondary to small intestinal tumors with gastrointestinal hemorrhage as the main symptom. PATIENT CONCERNS: Two men aged 19 and 54 years were successively referred to our department due to intermittent hematochezia. The hemoglobin levels of the two patients declined progressively, and conservative treatment was ineffective. DIAGNOSES: The first patient underwent an abdominal computed tomography angiography examination, which showed that the intestine and its mesentery were tortuous, suggesting an intra-abdominal hernia or intussusception. The second patient underwent an abdominal computed tomography examination, which suggested a high possibility of an intussusception. The two patients were diagnosed as adult intussusception caused by small intestinal tumors. INTERVENTIONS: Emergency laparoscopic explorations were performed. Enteroenteric intussusceptions caused by ileal tumors were found during surgery. Reduction of the intussusceptions and resection of the ileal tumors were performed. OUTCOMES: The patients recovered well after surgery, and postoperative pathology showed that the tumors were a vascular hamartoma polyp and a lipoma. LESSONS: Adult intussusception is very rare, particularly with gastrointestinal hemorrhage as the main symptom. Isolated hamartoma polyp is a rare cause of intussusception in adults. The clinical manifestations of adult intussusception are very atypical, and thus, making a preoperative diagnosis is difficult. Abdominal CT or CTA is an effective diagnostic method for adult intussusception. For adult patients with gastrointestinal hemorrhage caused by intussusceptions, active surgery should be performed when conservative treatment is not effective. Laparoscopic surgery is a safe and effective treatment for adult intussusceptions caused by benign diseases.

Anti-cancer effect of low dose of celecoxib may be associated with lnc-SCD-1:13 and lnc-PTMS-1:3 but not COX-2 in NCI-N87 cells.

In order to investigate the mechanism of celecoxib and whether long non-coding RNAs (lncRNAs) were involved in the effects of celecoxib treatment in NCI-N87 cells, NCI-N87 cells were treated with 15, 30 and 60 µM celecoxib and an MTT assay was performed to assess cell viability. Following treatment with 15 µM celecoxib, the cell cycle and apoptosis were analyzed by flow cytometry, and the mRNA levels of lnc-SCD-1:13, lnc-PTMS-1:3, cyclooxygenase-2 (COX-2), integrin α3 (ITGA3) and DSH homolog 1 (DVL1) were detected by reverse transcription quantitative PCR (RT-qPCR) in NCI-N87 cells. MTT analysis demonstrated that celecoxib significantly inhibited cell viability in treated cells compared with untreated cells. Flow cytometry analysis revealed that, compared with untreated cells, the percentage of cells in the G0/G1 phase was significantly increased, and the percentage of cells in the S and G2 phase was decreased. In addition, the percentage of early and late apoptotic cells was increased in cells treated with 15 µM celecoxib compared with the control. RT-qPCR analysis also demonstrated that the mRNA levels of lnc-SCD-1:13, lnc-PTMS-1:3, ITGA3 and DVL1 were increased following treatment with celecoxib (15 µM; P<0.05). However, there were no significant differences in the expression of COX-2 mRNA between cells treated with celecoxib (15 µM) and untreated cells. The present study demonstrated that a low dose of celecoxib may be involved in regulating cell growth independent of COX-2 in NCI-N87 cells. Furthermore, ITGA3 and/or DVL1 co-expressed with lnc-SCD-1:13 and lnc-PTMS-1:3 may be associated with the effects of treatment with a low dose of celecoxib in NCI-N87 cells.

Hepatic portal venous gas associated with colon cancer: A case report and literature review.

RATIONALE: Hepatic portal venous gas (HPVG) is a very rare radiological finding that occurs when gas enters the portal venous system. HGVG can be caused by various diseases, with the most common being intestinal ischemia or necrosis. While there are few reports of HPVG associated with colon cancer, we report a case of HPVG associated with advanced colon cancer. DIAGNOSIS: The diagnosis of this patient was HPVG caused by colon cancer. INTERVENTIONS: Left colon cancer resection, pancreatic tail resection, splenectomy, and transverse colostomy were performed. OUTCOMES: The patient recovered well, and postoperative paraffin pathology confirmed that the resected tumor was colon cancer. LESSONS: Abdominal computed tomography is an effective method for diagnosing and monitoring HPVG. Klebsiella pneumonia is a potential gas-producing microorganism associated with HPVG, which may be confirmed by Blood culture or drainage culture. The prognosis of HPVG is closely related to the underlying pathology. Surgery should be performed early when there are signs of intestinal ischemia, necrosis, or perforation.

Comparative analysis of gene expression profiles of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma.

In the present study, gene expression profiles were analyzed to identify the molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA samples and 62 normal controls, as well as 72 GNCA samples and 72 normal controls. The two groups of differentially-expressed genes (DEGs) were compared to obtain common and unique DEGs. A differential analysis was performed using the Linear Models for Microarray Data package in R. Functional enrichment analysis was conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks were constructed for the DEGs with information from the Search Tool for the Retrieval of Interacting Genes. Subnetworks were extracted from the whole network with Cytoscape. Compared with the control, 284 and 268 genes were differentially-expressed in GCA and GNCA, respectively, of which 194 DEGs were common between GCA and GNCA. Common DEGs [e.g., claudin (CLDN)7, CLDN4 and CLDN3] were associated with cell adhesion and digestion. GCA-unique DEGs [e.g., MAD1 mitotic arrest deficient like 1, cyclin (CCN)B1, CCNB2 and CCNE1] were associated with the cell cycle and the regulation of cell proliferation, while GNCA-unique DEGs (e.g., GATA binding protein 6 and hyaluronoglucosaminidase 1) were implicated in cell death. A PPI network with 141 nodes and 446 edges were obtained, from which two subnetworks were extracted. Genes [e.g., fibronectin 1, collagen type I α2 chain (COL1A2) and COL1A1] from the two subnetworks were implicated in extracellular matrix organization. These common DEGs could advance our understanding of the etiology of gastric cancer, while the unique DEGs in GCA and GNCA could better define the properties of specific cancers and provide potential biomarkers for diagnosis, prognosis or therapy.

miR-582-5P induces colorectal cancer cell proliferation by targeting adenomatous polyposis coli.

BACKGROUND: microRNA (miRNAs) dysregulation is widely involved in cancer progression and contributed to sustained cell proliferation by directly targeting multiple targets. Therefore, better understand the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. METHODS: We assessed microRNA-582 (miR-582-5P) expression in colorectal cancer (CRC) specimens and cell lines by real-time PCR. Luciferase reporter assay was used to confirm the target associations. Colony formation assay and anchorage-independent growth assay were used to analyze the effect of miR-582-5P on cell proliferation. Adenomatous polyposis coli (APC) gene and protein expression were examined using real-time PCR and western blotting, respectively. RESULTS: miR-582-5P was upregulated in the CRC specimens and cell lines and targeted the 3' untranslated region of APC directly. miR-582-5P overexpression increased cyclin D1 and c-MYC expression, which subsequently induced CRC cell proliferation in an APC-dependent manner. CONCLUSIONS: Our findings suggest that miR-582-5P plays an important role in the progression of CRC by inducing proliferation and may identify new targets for anti-cancer treatment.

GRIM-19 expression is a potent prognostic marker in colorectal cancer.

Retinoid-interferon-induced mortality-19 (GRIM-19), a recently discovered cell death regulatory gene, may function as a tumor suppressor in many human malignancies. However, the expression of GRIM-19 in and its prognostic value for patients with colorectal cancer (CRC) have not been well investigated to date. Here, GRIM-19 expression was measured immunohistochemically in 94 colon samples and by quantitative real-time reverse transcriptase polymerase chain reaction in 15 paired CRC tissues and adjacent normal tissues. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Our results showed that GRIM-19 mRNA and protein levels in adenoma tissues were similar to those in adjacent normal tissues. However, GRIM-19 expression was severely depressed in carcinomas compared to matched normal tissues (P = .000). Additionally, we found GRIM-19 to be located in both the cytoplasm and nucleus in normal tissues but only in the cytoplasm in CRC tissues. Alteration in GRIM-19 expression occurs early in the pathogenesis of CRC; moreover, low GRIM-19 expression was associated with poor tumor differentiation (P = .013), the presence of lymph nodes (P = .000), metastasis to other organs (P = .045) and vascular invasion (P = .010). During a mean period of 40 months follow-up, patients without GRIM-19 had a statistically significantly lower rate of recurrence/metastasis (P < .05) and a shorter overall survival time (P < .01) than the patients with GRIM-19 expression. Taken together, GRIM-19 expression is closely associated with CRC progression and might be a very promising prognostic biomarker for CRC patients.

Influences of laparoscopic-assisted gastrectomy and open gastrectomy on serum interleukin-6 levels in patients with gastric cancer among Asian populations: a systematic review.

BACKGROUND: To compare the effects of laparoscopic-assisted gastrectomy (LAG) and open gastrectomy (OG) on serum interleukin-6 (IL-6) levels in gastric cancer (GC) patients from Asia. METHODS: The following scientific literature databases were searched for relevant clinical studies: PubMed, EBSCO, Ovid, Wiley, Web of Science, Cochrane library, EMBASE, WANFANG and VIP databases. The studies retrieved from database searches were screened based on stringent inclusion and exclusion criteria to select high quality cohort studies for the present meta-analysis. The data extracted from final selected studies were analyzed using STATA 12.0 software. RESULTS: A total of 54 studies were initially retrieved from database searches, and 11 clinical cohort studies were eventually enrolled in this meta-analysis. The 11 selected studies contained a combined total of 767 GC patients (427 patients in LAG group and 340 patients in OG group). Meta-analysis results demonstrated that postoperative serum IL-6 levels in GC patients in LAG group was significantly lower than the OG group (SMD = -2.16, 95% CI = -3.19 ~ -1.14, P < 0.001). The difference in serum IL-6 levels between the preoperative and postoperative GC patients was significantly lower in the LAG group compared to the difference found in the OG group (SMD = -3.44, 95% CI = -4.87 ~ -2.01, P < 0.001). Subgroup analysis based on country showed that, in both Chinese and Japanese GC patients, the postoperative increase in serum IL-6 levels in LAG group were significantly lower than the increase observed in the OG group (all P < 0.05). In Korean GC patients, the postoperative increase in serum IL-6 levels was not significantly different between the LAG group and OG group (all P > 0.05). CONCLUSION: Our results provide strong evidence that LAG is associated with significantly lower serum IL-6 levels, compared to OG. Thus, LAG carries markedly lower risk of adverse inflammatory reactions in GC patients among Asian population.

Association of single nucleotide polymorphisms of ERCC1 and XPF with colorectal cancer risk and interaction with tobacco use.

We investigated the association between polymorphisms in excision repair cross-complementation group 1 (ERCC1) (rs3212986, rs2298881 and rs11615) and xeroderma pigmentosum-complementation group F (XPF) (rs2276466 and rs6498486) and risk of colorectal cancer. A 1:1 matched case-control study was conducted. Conditional regression analysis indicated that individuals carrying the ERCC1 rs3212986 TT genotype and T allele had a marginally increased risk of colorectal cancer when compared with subjects with the GG genotype. Similarly, subjects carrying the rs11615 TT genotype and T allele had a marginally increased risk of colorectal cancer when compared with those with the CC genotype. Stratified analysis revealed that individuals with rs3212986 TT who were current or former smokers had a significantly increased risk of colorectal cancer, and a significant interaction was found between this SNP and cigarette smoking. In conclusion, our study suggests that rs3212986 and rs11615 polymorphisms are associated with risk of colorectal cancer in a Chinese population, particularly in smokers. This finding could be useful in revealing the genetic characteristics of colorectal cancer, and suggests more effective strategies for prevention and treatment.

[Predictive value of tumor vessel density from enhanced spiral CT scan for lymph node and distant metastasis of colorectal cancer].

OBJECTIVE: To test whether the tumor vessel density (TVD) from the enhanced spiral CT can preoperatively predict nodal status and distant metastasis of colorectal cancer. METHODS: Forty cases of colorectal cancer patients who received surgical treatment were included in this study. The three dimensional tumor vessels were reconstructed by an enhanced CT 64-slice spiral CT and its AW4.4 image processing platform. The TVD was measured by the 1000 high-resolution color graphics pathological analysis system. The TVD level was compared between different tumor size, classification, and TNM stage. The postoperative pathological staging was taken as golden standard. RESULTS: The sensitivity, specificity and accuracy for direct prediction of lymph node metastasis by the enhanced CT 64-slice spiral CT was 74.1%(20/27), 53.8%(7/13) and 67.5%(27/40) respectively. The TVD from the reconstructed three dimensional tumor vessels in the group with lymph node metastasis was significantly higher than that without metastasis(0.070±0.046 vs. 0.037±0.013, P<0.05). The TVD in the distant metastasis group was significantly higher than that without distant metastasis (0.130±0.032 vs. 0.049±0.030, P<0.01). No difference of TVD was found between different tumor size, invasion depth, and differentiation type. CONCLUSION: TVD level from the reconstructed three dimensional tumor vessels can indicate lymph node and distant metastasis of colorectal cancer.

Laparoscopic versus open resection of gastric gastrointestinal stromal tumors.

The aims of this study were to explore whether laparoscopic surgical resections of gastric gastrointestinal stromal tumors (GISTs) would produce better perioperative and similar oncologic outcomes compared with open surgical resection in Chinese patients. Thirty-six gastric GISTs cases were divided into a minimally invasive laparoscopic group and open resection group, depending on the surgical approach that was used. The general preoperative information, operative time, incision length, intraoperative blood loss, postoperative time to first flatulence, postoperative complications, postoperative hospital stay, total hospitalization costs, and such follow-up data as recurrence, metastasis, and mortality rates were compared between two groups. Among the 36 gastric GISTs, 15 received laparoscopic surgical treatment (laparoscopy group, n=15), and 21 received routine open resection treatment (open resection group, n=21). The laparoscopy group and the open resection group showed statistically significant differences (P<0.05) in incision length (7.8±2.3 vs. 16.9±3.8 cm), postoperative time to first flatulence (3.8±1.3 vs. 5.1±2.1 d), postoperative hospitalization time (7.6±2.5 vs. 11.3±3.7 d), and total cost of hospitalization (RMB 28,239±5,521 vs. RMB 23,761±5,362). There were no statistically significant differences (P>0.05) between the laparoscopy group and the open resection group in operative time (147.8±59.3 vs. 139.2±62.1 min) and intraoperative blood loss (149.8±98.9 vs. 154.2±99.3 mL). Both groups had no postoperative complications, no recurrence and metastasis, and no postoperative mortality. There were no statistically significant differences between the two groups in postoperative complications, postoperative recurrence and metastasis, and postoperative mortality. In conclusion, compared with open resection, the laparoscopic resection of gastric GISTs offers the advantages of less trauma, faster recovery, and shorter hospital stay.