Autophagy in cancer immunotherapy: Perspective on immune evasion and cell death interactions.

Both the innate and adaptive immune systems work together to produce immunity. Cancer immunotherapy is a novel approach to tumor suppression that has arisen in response to the ineffectiveness of traditional treatments like radiation and chemotherapy. On the other hand, immune evasion can diminish immunotherapy's efficacy. There has been a lot of focus in recent years on autophagy and other underlying mechanisms that impact the possibility of cancer immunotherapy. The primary feature of autophagy is the synthesis of autophagosomes, which engulf cytoplasmic components and destroy them by lysosomal degradation. The planned cell death mechanism known as autophagy can have opposite effects on carcinogenesis, either increasing or decreasing it. It is autophagy's job to maintain the balance and proper functioning of immune cells like B cells, T cells, and others. In addition, autophagy controls whether macrophages adopt the immunomodulatory M1 or M2 phenotype. The ability of autophagy to control the innate and adaptive immune systems is noteworthy. Interleukins and chemokines are immunological checkpoint chemicals that autophagy regulates. Reducing antigen presentation to induce immunological tolerance is another mechanism by which autophagy promotes cancer survival. Therefore, targeting autophagy is of importance for enhancing potential of cancer immunotherapy.

Activation of RhoA/ROCK2 signaling by hypoxia-inducible factor 1α in promoting tumor growth and metastasis in human colon cancer.

Background: Recent evidence strongly suggests the profound role of the tumor microenvironment in cancer development and progression. A hypoxic microenvironment is widely acknowledged to be a typical feature of solid tumors, and altered hypoxia-inducible factor 1α (HIF-1α) expression has been associated with the formation and the progression of many solid tumors; however, the underlying mechanism of this relationship remains obscure. Methods: Clinical colorectal cancer tissue samples were collected to detect the differential expression of HIF-1α, Ras homolog family member A (RhoA), and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2). With hypoxic stress, small interfering RNA (siRNA) targeting HIF-1α, lentivirus transfection of RhoA was used to study the mechanism of HIF-1α and RhoA/ROCK2 signaling pathways in the growth and metastasis of colon cancer. Results: According to Cell Counting Kit 8, wound-healing, and Transwell assays, HIF-1α expression activated the RhoA/ROCK2 pathway within colon cancer cell lines, accelerating their growth and expansion. In cells transfected with LV-RhoA, inactivating the RhoA/ROCK2 pathway with the specific inhibitor Y-27632 decreased tumor growth and metastasis under hypoxic conditions, while activating the RhoA/ROCK2 pathway restored these biological properties. The Western blot results showed that the expression levels of pMYPT1, cyclin D1, and MMP2 in the siRNA + LV-RhoA group were also significantly increased compared with those in the siRNA group. Conclusions: For the first time, this study demonstrated that HIF-1α can promote the growth and metastasis of colon cancer via directly affecting RhoA/ROCK2 signaling and thus represents a novel therapeutic target for colon cancer.

Constructing defective-functionalized g-C3N4 homojunction for efficient photocatalytic detoxification of lemon yellow in an aqueous solution and beverage.

The content of food colorant in food and environment should be limited to a safe range. Thus, cost-effective, and environmental-friendly detoxification technology is urgent for food safety and environmental protection. In this work, defective-functionalized g-C3N4 was successfully fabricated via intermediate engineering strategy. The prepared g-C3N4 possesses large specific surface area with abundant in-plane pores. Carbon vacancy and N-CO unit are introduced into g-C3N4 molecular framework, endowing the different degrees of n-type conductivity in varied domains. And then the n-n homojunction is generated. This homojunction structure is demonstrated to be efficient in separation and transfer of photoinduced charge carriers, and causes enhanced photocatalytic detoxification of lemon yellow under visible light. Furthermore, as-prepared g-C3N4 in lemon tea enable completely removed lemon yellow without obvious effect on its overall acceptability. The findings deepen the understanding on the defect-induced self-functionality of g-C3N4, and prove the application potential of photocatalytic technology in contaminated beverages.

Identification and validation of a novel prognostic circadian rhythm-related gene signature for stomach adenocarcinoma.

Circadian rhythm genes were reported to be strongly associated with the development and prognosis of circadian rhythm disorders related to stomach adenocarcinoma (STAD), which is one of the most prevalent cancers. This study aimed to identify a circadian rhythm-related gene signature that could help predict STAD outcome. Using bioinformatics analysis approaches, 105 genes were examined in 350 patients with STAD. Overall, six hub-type circadian rhythm-associated genes (GNA11, PER1, SOX14, EZH2, MAGED1, and NR1D1) were identified using univariate and multivariate Cox regression analyses. These genes were then used to build a genetic predictive model, which was further validated using a publicly available dataset (GSE26899). Overall, genes associated with the circadian rhythm were found to be substantially correlated with the characteristics of the STAD patients (grade, sex, and M stage). In addition, the circadian rhythm-related gene signature was significantly associated with the MAPK and Notch signaling pathways, which are known risk factors for poorer STAD outcome. Taken together, these findings suggest that the herein proposed prognostic model based on six circadian rhythm-associated genes may have predictive value and potential application for clinical decision-making and for personalized treatment of STAD.

Copper catalysed protoboration of allenyl-Bdans: efficient synthesis of ß-boryl allyl-Bdans.

An efficient Cu-catalysed protoboration of allenyl-Bdans is presented. Under the optimized reaction conditions, a series of allenyl-Bdans reacted smoothly with B2Pin2 to afford ß-boryl allyl-Bdans in moderate to high yields with excellent regio- and stereoselectivity.

Variation of the ileocolic artery and superior mesenteric artery in a patient with right-sided colon cancer with Lynch syndrome: a case report.

Background: Complete mesangectomy and central vascular detachment are the core elements of laparoscopic right hemicolectomy. Failure to identify vascular variations in patients undergoing laparoscopic right hemicolectomy can result in unwanted bleeding, a prolonged surgical time, transfer to open surgery, and an elevated risk of postoperative complications. In this case report, we describe a new vascular variation that has not yet been reported in the literature. Parallelly vascular variation and the management of vessels in key areas are essential for successful surgery. Case Description: The patient was a 32-year-old female who was referred to the department of gastrointestinal surgery of our hospital due to intermittent abdominal pain accompanied by changes in stool habits for 3 months. She had not experienced other symptoms. Physical examination revealed mild tenderness in the right lower abdomen. Subsequently, she underwent laparoscopic radical right hemicolectomy for ascending colon cancer under general anesthesia in our hospital. Preoperative abdominal contrast-enhanced computed tomography (CT) and intraoperative photos confirmed that there were two ileocolic arteries derived from the superior mesenteric artery (SMA). On the other side, the SMA and superior mesenteric vein (SMV) were found to be accompanied like "X"-shaped variant. The final surgical pathological diagnosis was pT3N1aM0 adenocarcinoma of the ascending colon. Given the patient's family history of colon and uterine cancer combined with the results of immunohistochemical staining and next-generation sequencing, we concluded that she had Lynch syndrome (LS). Conclusions: This report describes the first case of simultaneous variation of the ileocolic artery (ICA) and SMA in a female patient with colon cancer. This type of vascular variation should be fully recognized by surgeons in order to avoid unnecessary intraoperative bleeding.

TrustGWAS: A full-process workflow for encrypted GWAS using multi-key homomorphic encryption and pseudorandom number perturbation.

The statistical power of genome-wide association studies (GWASs) is affected by the effective sample size. However, the privacy and security concerns associated with individual-level genotype data pose great challenges for cross-institutional cooperation. The full-process cryptographic solutions are in demand but have not been covered, especially the essential principal-component analysis (PCA). Here, we present TrustGWAS, a complete solution for secure, large-scale GWAS, recapitulating gold standard results against PLINK without compromising privacy and supporting basic PLINK steps including quality control, linkage disequilibrium pruning, PCA, chi-square test, Cochran-Armitage trend test, covariate-supported logistic regression and linear regression, and their sequential combinations. TrustGWAS leverages pseudorandom number perturbations for PCA and multiparty scheme of multi-key homomorphic encryption for all other modules. TrustGWAS can evaluate 100,000 individuals with 1 million variants and complete QC-LD-PCA-regression workflow within 50 h. We further successfully discover gene loci associated with fasting blood glucose, consistent with the findings of the ChinaMAP project.

[Corrigendum] miR­647 and miR­1914 promote cancer progression equivalently by downregulating nuclear factor IX in colorectal cancer.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in the scratch­wound assays shown in Fig. 3A on p. 8195, the data shown for the '0 h/NC' and '0 h/miR­1914 antagomir' data panels appeared to be strikingly similar, such that they may have been derived from the same original source. The authors have consulted their original data, and realize that the '0 h/miR­1914 antagomir' data panel was inadvertently selected incorrectly for Fig. 3A. The corrected version of Fig. 3, now showing the correct data for the '0 h/miR­1914 antagomir' data panel in Fig. 3A, is shown on the next page. Note that the errors in Fig. 3 did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 16, 8189­8199, 2017; DOI: 10.3892/mmr.2017.7675].

Synergistic Pd/Cu-catalysed regio- and stereoselective borylation of allenylic carbonates.

A simple Pd/Cu-catalyzed borylation of allenylic carbonates with B2Pin2 was developed using a cheap P(OEt)3 ligand. Under mild neutral conditions, 2-boryl 1,3-butadienes were obtained selectively in moderate to high yields. Furthermore, the use of different diboron reagents was also feasible in the reaction.

Construction of a gut microbiota-gene-pathway network to reveal the molecular mechanisms underlying right- and left-sided colorectal cancer.

Aiming to reveal the molecular mechanisms involved in right- and left-sided colorectal cancer (CRC) development, CRC gene expression data and a microorganism atlas were downloaded from The Cancer Genome Atlas and The Cancer Microbiome Atlas, respectively. The R package was used to screen differentially expressed genes (DEGs) between right- and left-sided CRC samples and identify those related to prognosis, a correlation analysis was performed between DEGs and prognosis-related microbiota, and an interaction network was created using Cytoscape. Finally, a taxon set enrichment analysis of the microbiota was performed and a gene-genus-pathway network was constructed after GO and KEGG analyses. In total, nine out of 1557 identified DEGs had a significant correlation with prognosis, whereas three out of 211 bacterial genera (Fusobacterium, Bacteroides and Parabacteroides) showed a significant correlation with prognosis. DEGs were mainly enriched in the PPAR pathway and vitamin metabolic and transport processes. According to a taxon set enrichment analysis, the microbes in the integrated network were significantly abundant in 28 host-intrinsic, two host-extrinsic and one environment taxon sets. This study provides new insights for understanding the molecular mechanisms of left- and right-CRC.

Maximal voluntary ventilation and forced vital capacity of pulmonary function are independent prognostic factors in colorectal cancer patients: A retrospective study of 2323 cases in a single-center of China.

ABSTRACT: Preoperative pulmonary function assessment is applied to select surgical candidates and predict the occurrence of postoperative complications. This present study enrolled 2323 colorectal cancer patients. Forced vital capacity (FVC) and maximal voluntary ventilation (MVV) were measured as predicted values. Associations between patient pulmonary function and both prognosis and postoperative complications was analyzed. The value of FVC and MVV optimal cutoff was 98.1 (P < .001) and 92.5 (P < .001), respectively. Low FVC and low MVV were associated with higher rates of postoperative fever (23.8% vs 13.9%, P < .001; 17.8% vs 13.3%, P = .049, respectively) and with higher rates of pneumonia (3.75% vs 1.73%, P = .002; 3.00% vs 1.71%, P = .009, respectively), pleural effusion (3.00% vs 1.57%, P = .033; 3.18% vs 1.42%, P = .006, respectively), and poor patient prognosis (5-year overall survival: 80.0% vs 90.3%, P < .001; 71.7% vs 91.9%, P < .001, respectively). In addition, low FVC was closely related to the higher rate of anastomosis leak (4.31% vs 2.29%, P = .013), low MVV was correlated with the higher rate of uroschesis (2.38% vs 0.65%, P < .001). In subgroup analyses, the predictive value of FVC and MVV in patients with different tumor stage was analyzed. Both low FVC and MVV were independent risk factors for poor prognosis in stage II and III, indicating that low FVC and MVV are predictive of poorer prognosis and higher risk of postoperative complications in colorectal cancer patients.

[Research progress of sacral neuromodulation procedure in the treatment of chronic constipation and fecal incontinence].

Sacral neuromodulation(SNM) procedure has become a new therapy to treat chronic constipation and fecal incontinence. The surgical procedure is easy and safe. It has a small incision compared with traditional surgery and is mainly used in patients whose traditional treatment was unsuccessful. Chronic constipation is one of the most common digestive symptoms. The quality of life in patients with severe constipation has decreased greatly. Although the incidence of fecal incontinence in China is not as high as that of constipation, it also seriously affects the life of the patients, resulting in a decline in the quality of life. Although the mechanism of SNM is uncertain, with more studies conducted, understanding has become more profound, and the curative effect has been recognized. SNM can improve the symptoms and the quality of life. Many studies have reported SNM treatment. Furthermore, some trials on SNM have been conducted. It is used after colorectal resections to promote symptoms of bowel dysfunction. However, few studies reported regarding SNM for constipation and fecal incontinence in China, and knowledge regarding SNM is limited. In this article, we will mainly discuss SNM in the treatment of chronic constipation and fecal incontinence, and its research progress on the mechanism and method, surgical procedure, effectiveness, complications, postoperative contraindications, and the population who need to pay attention, in order to provide reference for the treatment of SNM in China.

miR­647 and miR­1914 promote cancer progression equivalently by downregulating nuclear factor IX in colorectal cancer.

MicroRNAs (miRNAs/miRs) have been investigated as diagnostic and prognostic biomarkers for cancer; however, the significance of miRNAs in colorectal cancer (CRC) remains to be elucidated. The aim of the present study was to determine the genetic profiles of CRC tissue, and screen for miRNAs implicated in CRC cell proliferation and migration. RNA sequencing of 10 paired specimens was performed to for screen genes that were upregulated or downregulated in CRC. miRNA expression in CRC specimens and cell lines was confirmed using qPCR analysis. The significance of indicated miRNAs in CRC cell proliferation and migration was evaluated using MTT and scratch wound­healing assays. Online computational prediction, isobaric tags for relative and absolute quantification analysis and a luciferase reporter assay were applied to determine candidate targeted genes for the miRNAs. RNA­seq data revealed miR­1914 as the most prominent miRNA in CRC specimens. qPCR analysis also suggested that the expression of miR­1914, as well as its counterpart miR­647 were elevated in CRC specimens and cell lines. Suppression of miR­647/1914 using small interfering RNAs inhibited CRC SW480 and SW620 cell proliferation, and migration. Nuclear factor I/X (NFIX) was demonstrated to be a candidate for miR­647/1914 and mediated the oncogenic activity of miR­647/1914. In all, miR­647 and miR­1914 were demonstrated to promote the proliferation and migration of CRC cells by directly targeting NFIX. Therapeutic delivery of siRNAs targeting miR­647/1914 and overexpression of NFIX may be feasible approaches for CRC treatment.

DDX5 promotes gastric cancer cell proliferation in vitro and in vivo through mTOR signaling pathway.

DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) is an ATP-dependent RNA helicase that is overexpressed in various malignancies. Increasing evidence suggests that DDX5 participates in carcinogenesis and cancer progression via promoting cell proliferation and metastasis. However, the functional role of DDX5 in gastric cancer is largely unknown. In this study, we observed that DDX5 was significantly up-regulated in gastric cancer tissues compared with the paired adjacent normal tissues. The expression of DDX5 correlated strongly with Ki67 index and pathological stage of gastric cancer. In vitro and in vivo studies suggested that knockdown of DDX5 inhibited gastric cancer cell proliferation, colony formation and xenografts growth, whereas ectopic expression of DDX5 promoted these cellular functions. Mechanically, DDX5 induced gastric cancer cell growth by activating mTOR/S6K1. Treatment of everolimus, the specific mTOR inhibitor, significantly attenuated DDX5-mediated cell proliferation. Interestingly, the expression of DDX5 and p-mTOR in gastric cancer tissues demonstrated a positive correlation. Taken together, these results revealed a novel role of DDX5 in gastric cancer cell proliferation via the mTOR pathway. Therefore, DDX5 may serve as a therapeutic target in gastric cancer.

[Sacral neuromodulation in the treatment of intractable constipation].

OBJECTIVE: To assess the efficacy of sacral neuromodulation (SNM) in patients with intractable constipation. METHODS: A total of 7 patients with intractable constipation were treated with pereutaneous test stimulation of the S3 nerve root and were assessed by sacral never stimulation system in our department from January 2013 to January 2014. Four of these 7 patients received operation for constipation before. The efficacy was assessed by bowel habit diary, clinic constipation scores, subjective questionnaire and clinical signs. RESULTS: The constipation symptoms were improved significantly in all the 7 patients. The frequency and volume of defecation per week were increased obviously, and the average urine was increased. Six patients underwent permanent implantation of the SNS system. After a median 4 months follow-up, the defecation frequency increased from 0.6 ± 0.5 to 8.0 ± 2.5 per week (P<0.01), and the defecation time decreased from (22.9 ± 11.5) to (3.7 ± 0.8) min (P<0.01). The Cleveland clinic constipation score decreased from 24.6 ± 4.2 to 9.0 ± 0.9 (P<0.01), and the visual analogue scale(VAS) score increased from 8.1 ± 0.9 to 82.5 ± 5.2 (P<0.01). CONCLUSION: SNM is a clinically efficacious, minimally invasive and safe new technique, which offers an alternative treatment for the patients with intractable constipation resistant to conservative treatment, especially for the patients refractory to traditional operations.

Increased MMP-21 expression in esophageal squamous cell carcinoma is associated with progression and prognosis.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy, requiring effective biomarkers for prognosis and therapeutic responsiveness. In this retrospective study of banked pathology material, we investigated the protein expression of MMP-21 in ESCC and its association with clinical significance. MMP-21 protein expression was investigated in 311 cases of ESCC by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of MMP-21 expression with clinicopathological characteristics and overall survival of patients with ESCC. Results showed that MMP-21 expression was significantly increased in ESCC (P < 0.001). It was also found that MMP-21 expression in ESCC was associated with tumor invasion (P < 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and TNM stage (P < 0.001). Kaplan-Meier analysis showed MMP-21 expression was associated with overall survival of patients with ESCC for patients with tumors of positive MMP-21 staining tend to have worse overall survival (P < 0.001). Multivariate analysis proved that MMP-21 was an independent prognostic factor for overall survival for patients with ESCC (P < 0.001). These results suggested the potential role of MMP-21 in tumor progression and prognosis predication of human ESCC. It might also be a novel molecular target for therapeutic intervention.

[Construction and expression of eukaryotic expression plasmid pcDNA3.1-smac].

AIM: To construct the eukaryotic expression vector of human gene Smac pcDNA3.1-Smac and express it in the lung adenocarcinoma A549 cells. METHODS: The Smac was amplified from human testis tissue by reverse transcriptase polymerase chain reaction (RT-PCR). Then recombined eukaryotic expression vector pcDNA3.1-Smac was constructed. After the reconbinant plasmid was proved to be constructed correctly by endonucleases digesting and DNA sequencing, we trasfected it into lung adenocarcinama cells A549 through liposome inducing. The expression of Smac in transfectant A549 was detected by RT-PCR and Western blot. And the cell growth inhibition ratio after trasfection was detected by MTT. RESULTS: The amplified fragment by PCR was coincident with the anticipated result, and its sequence was in concordance with that published on GenBank.Therefore, the gene Smac was cloned successfully, and the recombinant plasmid pcDNA3.1-Smac was also constructed successfully. Both on the mRNA level and the protein level, the expression of Smac gene was increased obviously in the transfected A549 detected by RT-PCR and Western blot respectively. The cell growth inhibition ratio in the group transfected pcDNA3.1-Smac was significantly higher compared with the pcDNA3.1 group after 72 hours. CONCLUSION: The recombinant eukaryotic expression vector pcDNA3.1-Smac was constructed, and it could be obviously expressed in lung adenocarcinoma cells A549. It is also proven that Smac has the function of growth inhibition.