Securinine inhibits carcinogenesis in gastric cancer by targeting AURKA-ß-catenin/Akt/STAT3 and the cell cycle pathway.

BACKGROUND: Gastric cancer (GC) is difficult to treat with currently available treatments. Securinine (SCR) has a lengthy history of use in the treatment of disorders of the nervous system, and its anticancer potential has been gaining attention in recent years. The aim of this study was to explore the repressive effect of SCR on GC and its fundamental mechanism. METHODS: The efficacy of SCR in GC cells was detected by MTT assays. Colony formation, flow cytometry and Transwell assays were used to assess the changes in the proliferation, apoptosis, cell cycle distribution, migration and invasion of GC cells after treatment. AGS (human gastric carcinoma cell)-derived xenografts were used to observe the effect of SCR on tumor growth in vivo. The molecular mechanism of action of SCR in GC was explored via RNA sequencing, bioinformatics analysis, Western blotting, molecular docking, and immunohistochemistry. RESULTS: SCR was first discovered to inhibit the proliferation, migration, and invasion of GC cells while initiating apoptosis and cell cycle arrest in vitro. It was also established that SCR has excellent anticancer effects in vivo. Interestingly, AURKA acts as a crucial target of SCR, and AURKA expression can be blocked by SCR. Moreover, this study revealed that SCR suppresses the cell cycle and the ß-catenin/Akt/STAT3 pathways, which were previously reported to be regulated by AURKA. CONCLUSION: SCR exerts a notable anticancer effect on GC by targeting AURKA and blocking the cell cycle and ß-catenin/Akt/STAT3 pathway. Thus, SCR is a promising pharmacological option for the treatment of GC.

Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia.

BACKGROUND: This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. METHODS: 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. RESULTS: 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The ß-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. CONCLUSION: This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.

Long non-coding RNA HANR modulates the glucose metabolism of triple negative breast cancer via stabilizing hexokinase 2.

Increasing evidence has demonstrated the oncogenic roles of long non-coding RNA (lncRNA) hepatocellular carcinoma (HCC)-associated long non-coding RNA (HANR) in the development of HCC and lung cancer; however, the involvement of HANR in triple-negative breast cancer (TNBC) remains largely unknown. Our results demonstrated the significant overexpression of HANR in TNBC tissues and cells. Higher HANR levels significantly correlated with the poorer phenotypes in patients with TNBC. HANR down-regulation inhibited the proliferation and cell cycle progression and increased the apoptosis of TNBC cells. Mechanistically, immunoprecipitation-mass spectrometry revealed hexokinase II (HK2) as a direct binding target of HANR. HANR binds to and stabilizes HK2 through the proteasomal pathway. Consistent with the important role of HK2 in cancer cells, HANR depletion represses the glucose absorbance and lactate secretion, thus reprogramming the metabolism of TNBC cells. An in vivo xenograft model also demonstrated that HANR promoted tumor growth and aerobic glycolysis. This study reveals the role of HANR in modulating the glycolysis in TNBC cells by regulating HK2 stability, suggesting that HANR is a potential drug target for TNBC.

siRNA-based approaches for castration-resistant prostate cancer therapy targeting the androgen receptor signaling pathway.

Androgen deprivation therapy is a common treatment method for metastatic prostate cancer through lowering androgen levels; however, this therapy frequently leads to the development of castration-resistant prostate cancer (CRPC). This is attributed to the activation of the androgen receptor (AR) signaling pathway. Current treatments targeting AR are often ineffective mostly due to AR gene overexpression and mutations, as well as the presence of splice variants that accelerate CRPC progression. Thus there is a critical need for more specific medication to treat CRPC. Small interfering RNAs have shown great potential as a targeted therapy. This review discusses prostate cancer progression and the role of AR signaling in CRPC, and proposes siRNA-based targeted therapy as a promising strategy for CRPC.

Multimodal prehabilitation to improve the clinical outcomes of frail elderly patients with gastric cancer: a study protocol for a multicentre randomised controlled trial (GISSG+2201).

INTRODUCTION: Gastric cancer (GC) diagnosed in the elderly population has become a serious public health problem worldwide. Given the combined effects of frailty and the consequences of cancer treatment, older individuals with GC are more likely than young patients to suffer from postoperative complications and poor clinical outcomes. Nutrition, functional capacity and psychological state-based multimodal prehabilitation, which is dominated by Enhanced Recovery After Surgery (ERAS) pathway management, has been shown to reduce postoperative complications, promote functional recovery and decrease hospitalisation time in certain malignancies. However, no previous studies have investigated the clinical application of multimodal prehabilitation in frail older patients with GC. METHODS AND ANALYSIS: The study is a prospective, multicentre randomised controlled trial in which a total of 368 participants who meet the inclusion criteria will be randomised into either a prehabilitation group or an ERAS group. The prehabilitation group will receive multimodal prehabilitation combined with ERAS at least 2 weeks before the gastrectomy is performed, including physical and respiratory training, nutritional support, and therapy and psychosocial treatment. The ERAS group patients will be treated according to the ERAS pathway. All interventions will be supervised by family members. The primary outcome measures are the incidence and severity of postoperative complications. Secondary outcomes include survival, functional capacity and other short-term postoperative outcomes. Overall, the multimodal prehabilitation protocol may improve functional capacity, reduce the surgical stress response and concomitant systemic inflammation, and potentially modulate the tumour microenvironment to improve short-term and long-term clinical outcomes and patients' quality of life. ETHICS AND DISSEMINATION: All procedures and participating centres of this study were approved by their respective ethics committees (QYFYKYLL 916111920). The final study results will be published separately in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05352802.

(R)-9bMS Inhibited the Protein Synthesis and Autophagy of Triple Negative Breast Cancer Cells via Regulating miR-4660/mTOR Axis.

BACKGROUND: Unlike other subtypes of breast cancer, triple negative breast cancer (TNBC) exhibits aggressive and metastatic behaviors and a lack of effective targeted therapeutics. (R)-9bMS, a small-molecule inhibitor of the non-receptor tyrosine kinase 2 (TNK2), significantly inhibited TNBC cell growth; however, the functional mechanism of (R)-9bMS in TNBC remains largely unknown. OBJECTIVE: To explore the functional mechanism of (R)-9bMS in TNBC. METHODS: Cell proliferation, apoptosis and xenograft tumor growth assays were performed to evaluate the effects of (R)-9bMS on TNBC. The expression levels of miRNA and protein were detected by RTqPCR or western blot, respectively. Protein synthesis was determined by analyzing the polysome profile and 35S-met incorporation. RESULTS: (R)-9bMS attenuated TNBC cell proliferation, induced cell apoptosis, and inhibited xenograft tumor growth. Mechanism study indicated that (R)-9bMS upregulated the expression of miR-4660 in TNBC cells. The expression of miR-4660 is lower in TNBC samples than that of the non-cancerous tissues. miR-4660 overexpression inhibited TNBC cell proliferation by targeting the mammalian target of rapamycin (mTOR), which reduced mTOR abundance in TNBC cells. Consistent with the downregulation of mTOR, exposure of (R)-9bMS inhibited the phosphorylation of p70S6K and 4E-BP1, which consequently interrupted the total protein synthesis and autophagy of TNBC cells. CONCLUSION: These findings uncovered the novel working mechanism of (R)-9bMS in TNBC by attenuating mTOR signaling via up-regulating miR-4660. The potential clinical significance of (R)- 9bMS in TNBC treatment is interesting to explore.

Examined lymph node numbers influence prognosis in rectal cancer treated with neoadjuvant therapy.

Background: The number of lymph nodes examined (LNe) is often insufficient in patients with rectal cancer (RC) treated with neoadjuvant therapy; however, its prognostic value remains controversial. Thus, we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy. Methods: Data were collected from seven prospective hospital databases in China from July 2002 to May 2018. Binary logistic regression models were used to predict lymph node metastasis. The cut-off value for LNe was determined using X-tile 3.6.1. Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model. Results: A total of 482 patients were included, of whom 459 had complete overall survival (OS) information. Using the percentile method, the total number of lymph nodes examined (TLNe) was 14-16 (40th-60th percentile), and the proportion of patients with lymph node metastasis reached a maximum of 48.1%. Cox multivariate analysis showed that the odds ratio (OR) remained the highest when TLNe was 14-16 (OR = 3.379, P = 0.003). The 3-year and 5-year OS were 85.4% and 77.8%, respectively. Negative lymph nodes examined (NLNe) of ≤6 was an independent risk factor for 3-year and 5-year OS (3-year OS 71.1% vs. 85.9%, P = 0.004; 5-year OS 66.3% vs. 74.3%, P = 0.035). Subgroup analysis for patients with ypN + showed that higher 3-year and 5-year OS were achieved when the TLNe was >10, 78.8% vs. 54.0% (P = 0.005), and 60.8% vs. 36.0% (P = 0.012), respectively. Patients with ypN0M0 had a higher 5-year OS when the TLNe was >19 (P = 0.055). Conclusion: The TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.

WSP from "Nostoc commune" Vauch. suppresses gastric cancer migration via EGFRVIII signaling.

Introduction: A number of evidences have proved that "Nostoc commune" Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of "Nostoc commune" Vauch extracellular matrix- a water-stress protein (WSP) still needs to be elucidated. Methods: In our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment. Results: We found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells. Discussion: Given the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.

MicroRNA-137 Inhibits Esophageal Squamous Cell Carcinoma by Downregulating DAAM1.

BACKGROUND: A growing body of evidence demonstrates that miR-137 acts against cancers; however, the biological function of miR-137 in esophageal squamous cell carcinoma (ESCC) remains to be fully understood. OBJECTIVE: The aim of this study is to explore the role of miR-137 in ESCC. METHODS: miR-137 expression was detected by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and target protein expression was detected by western blot. Cell counting, colony formation and flow cytometry were employed to determine the effects of miR-137 on the growth of ESCC cells. Dual-luciferase reporter assay was performed to validate the binding of miR- 137 with a dishevelled-associated activator of morphogenesis 1 (DAAM1) 3'-UTR. RESULTS: miR-137 was shown to be down-regulated in ESCC. miR-137 expression was inversely correlated with the 5-year survival rate of ESCC patients. Up-regulated miR-137 attenuated ESCC proliferation and promoted ESCC cell apoptosis. Meanwhile, to further reveal how miR-137 regulated the malignant behaviors of ESCC, the downstream mRNA binding targets of miR-137 were explored. miR-137 was demonstrated to bind DAAM1 3'-UTR and repressed the expression of DAAM1. The expression of DAAM1 and miR-137 in ESCC was inversely correlated. Additionally, the reintroduction of DAAM1 had the capacity to reverse the negative role of miR- 137 in ESCC cell growth. CONCLUSION: These findings have uncovered the new function of miR-137 in ESCC via negatively regulating DAAM1, suggesting miR-137 as a potent therapeutic candidate for ESCC treatment.

Long-term outcomes of laparoscopic Extralevator Abdominoperineal excision with modified position change for low rectal Cancer treatment.

BACKGROUND: Extralevator abdominoperineal excision (ELAPE) has been recommended for treating low rectal cancer due to its potential advantages in improving surgical safety and oncologic outcomes as compared to conventional abdominoperineal excision (APE). In ELAPE, however, whether the benefits of intraoperative position change to a prone jackknife position outweighs the associated risks remains controversial. This study is to introduce a modified position change in laparoscopic ELAPE and evaluate its feasibility, safety and the long-term therapeutic outcomes. METHODS: Medical records of 56 consecutive patients with low rectal cancer underwent laparoscopic ELAPE from November 2013 to September 2016 were retrospectively studied. In the operation, a perineal dissection in prone jackknife position was firstly performed and the laparoscopic procedure was then conducted in supine position. Patient characteristics, intraoperative and postoperative outcomes, pathologic and 5-year oncologic outcomes were analyzed. RESULTS: The mean operation time was 213.5 ± 29.4 min and the mean intraoperative blood loss was 152.7 ± 125.2 ml. All the tumors were totally resected, without intraoperative perforation, conversion to open surgery, postoperative 30-day death, and perioperative complications. All the patients achieved pelvic peritoneum reconstruction without the usage of biological mesh. During the follow-up period, perineal hernia was observed in 1 patient, impaired sexual function in 1 patient, and parastomal hernias in 3 patients. The local recurrence rate was 1.9% and distant metastasis was noted in 12 patients. The 5-year overall survival rate was 76.4% and the 5-year disease-free survival rate was 70.9%. CONCLUSIONS: Laparoscopic ELAPE with modified position change is a simplified, safe and feasible procedure with favorable outcomes. The pelvic peritoneum can be directly closed by the laparoscopic approach without the application of biological mesh.

Hepatic portal venous gas associated with rapid infusion of postoperative early enteral nutrition after radical total gastrectomy.

Hepatic portal venous gas (HPVG) is a rare and severe imaging manifestation for surgeons, and it may require emergency surgery. We report an unusual case of HPVG in association with the drip rate of enteral nutrition (EN) after laparoscopic-assisted radical total gastrectomy with Roux-en-Y reconstruction. A 66-year-old woman with gastric cancer was admitted to our hospital. She was diagnosed with cirrhosis of unknown cause and underwent radical total gastrectomy. The rapid infusion of postoperative early EN caused the intestine to expand quickly and injured intestinal mucosa. Hepatic portal venous gas and pneumatosis intestinalis (PI) were discovered subsequently. Early detection and timely effective intervention eventually and completely cured the patient; meanwhile, we avoided unnecessary exploratory laparotomy. Hepatic portal venous gas and PI after radical total gastrectomy can be cured with careful conservative management; the drip rate of EN should be tightly controlled and monitored during treatment after radical total gastrectomy.

Randomized Controlled Trial Comparing the Short-term Outcomes of Enhanced Recovery After Surgery and Conventional Care in Laparoscopic Distal Gastrectomy (GISSG1901).

OBJECTIVE: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after LDG. SUMMARY OF BACKGROUND DATA: Currently, the ERAS program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer. METHODS: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery, and laboratory outcomes were compared between the ERAS and conventional groups. RESULTS: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the 2 groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P < 0.001; 8.85 vs 7.27 days, P < 0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P < 0.001; 3.09 vs 1.13 days, P < 0.001; 2.85 vs 1.38 days, P < 0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day 3 were significantly lower and the hemoglobin levels on postoperative day 5 were significantly higher in the ERAS group than in the conventional group. CONCLUSION: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy.

Effect of preoperative CT angiography examination on the clinical outcome of patients with BMI ≥ 25.0 kg/m2 undergoing laparoscopic gastrectomy: study protocol for a multicentre randomized controlled trial.

BACKGROUND: Gastric cancer, which is the fifth most common malignancy and the third most common cause of cancer-related death, is particularly predominant in East Asian countries, such as China, Japan and Korea. It is a serious global health issue that causes a heavy financial burden for the government and family. To our knowledge, there are few reports of multicentre randomized controlled trials on the utilization of CT angiography (CTA) for patients who are histologically diagnosed with gastric cancer before surgery. Therefore, we planned this RCT to verify whether the utilization of CTA can change the short- and long-term clinical outcomes. METHOD: The GISSG 20-01 study is a multicentre, prospective, open-label clinical study that emphasises the application of CTA for patients who will undergo laparoscopic gastrectomy to prove its clinical findings. A total of 382 patients who meet the inclusion criteria will be recruited for the study and randomly divided into two groups in a 1:1 ratio: the CTA group (n = 191) and the non-CTA group (n = 191). Both groups will undergo upper abdomen enhanced CT, and the CTA group will also receive CT angiography. The primary endpoint of this trial is the volume of blood loss. The second primary endpoints are the number of retrieved lymph nodes, postoperative recovery course, hospitalization costs, length of hospitalization days, postoperative complications, 3-year OS and 3-year DFS. DISCUSSION: It is anticipated that the results of this trial will provide high-level evidence and have clinical value for the application of CTA in laparoscopic gastrectomy. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04636099. Registered November 19, 2020.

Prediction model for malignant pulmonary nodules based on cfMeDIP-seq and machine learning.

Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) is a new bisulfite-free technique, which can detect the whole-genome methylation of blood cell-free DNA (cfDNA). Using this technique, we identified differentially methylated regions (DMR) of cfDNA between lung tumors and normal controls. Based on the top 300 DMR, we built a random forest prediction model, which was able to distinguish malignant lung tumors from normal controls with high sensitivity and specificity of 91.0% and 93.3% (AUROC curve of 0.963). In summary, we reported a non-invasive prediction model that had good ability to distinguish malignant pulmonary nodules.

Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis.

BACKGROUND: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy. METHODS: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan-Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. RESULTS: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients. CONCLUSIONS: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

Long non­coding RNA SChLAP1 regulates the proliferation of triple negative breast cancer cells via the miR­524­5p/HMGA2 axis.

Long non­coding RNA (lncRNA) second chromosome locus associated with prostate­1 (SChLAP1), also named LINC00913, has been reported to accelerate the carcinogenesis of prostate cancer. The aim of this study was to explore the role and mechanism of SChLAP1 in triple negative breast cancer (TNBC). The expression of SChLAP1 in TNBC tissues and cells was determined by reverse transcription quantitative PCR. The effects of SChLAP1 on the growth of TNBC cells was evaluated by detecting cell viability, colony formation and apoptosis. The present study determined that SChLAP1 was upregulated in TNBC tissues and was associated with the long­distant lymph node metastasis of patients with TNBC. Knockdown of SChLAP1 significantly inhibited cell viability and colony formation, and triggered apoptosis of TNBC cells. Bioinformatics analysis suggested that SChLAP1 acted as a sponge of microRNA (miR)­524­5p and negatively modulated the expression of miR­524­5p. An inverse correlation was also identified between the expression levels of SChLAP1 and miR­524­5p in TNBC tissues. Furthermore, the results demonstrated that SChLAP1 interacted with miR­524­5p, and subsequently regulated the expression level of High Mobility Group AT­Hook 2 (HMGA2) in TNBC cells. It was also found that the overexpression of HMGA2 rescued the suppressed viability of TNBC cells induced by SChLAP1 knockdown. In conclusion, the present findings demonstrated that SChLAP1 modulated the malignant tumor behaviors of TNBC cells by regulating HMGA2 and subsequently restraining miR­524­5p.

Effects of perioperative enhanced recovery after surgery pathway management versus traditional management on the clinical outcomes of laparoscopic-assisted radical resection of distal gastric cancer: study protocol for a randomized controlled trial.

BACKGROUND: The incidence of gastric cancer in East Asia is much higher than the international average. Therefore, improving the prognosis of patients and establishing effective clinical pathways are important topics for the prevention and treatment of gastric cancer. At present, the enhanced recovery after surgery (ERAS) pathway is widely used in the field of gastric surgery. Many randomized controlled trial (RCT) studies have proven that the ERAS regimen can improve the short-term clinical outcomes of patients with gastric cancer. However, a prospective study on the effect of the ERAS pathway on the prognosis of patients with gastric cancer has not yet been reported. This trial aims to confirm whether the ERAS pathway can improve the disease-free survival and overall survival of patients undergoing laparoscopic-assisted radical resection for distal gastric cancer. METHODS/DESIGN: This study is a prospective, multicentre RCT. This experiment will consist of two groups - an experimental group and a control group - randomly divided in a 1:1 ratio. The perioperative period of the experimental group will be managed according to the ERAS pathway and that of the control group will be managed according to the traditional management mode. An estimated 400 patients will be enrolled. The main endpoint for comparison is the 3-year overall survival and disease-free survival between the two groups. DISCUSSION: The results of this RCT should clarify whether the ERAS pathway is superior to traditional treatment on inflammatory indexes, short-term clinical outcome and survival for laparoscopic-assisted radical resection of distal gastric cancer. It is hoped that our data will provide evidence that the ERAS pathway improves survival in patients with gastric cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry, CHiCTR1900022438. Registered on 11 April 2019.

Prognostic Factors for Primary Localized Gastrointestinal Stromal Tumors After Radical Resection: Shandong Gastrointestinal Surgery Study Group, Study 1201.

BACKGROUND: Most previous risk-prediction models for gastrointestinal stromal tumors (GISTs) were based on Western populations. In the current study, we collected data from 23 hospitals in Shandong Province, China, and used the data to examine prognostic factors in Chinese patients and establish a new recurrence-free survival (RFS) prediction model. METHODS: Records were analyzed for 5285 GIST patients. Independent prognostic factors were identified using Cox models. Receiver operating characteristic curve analysis was used to compare a novel RFS prediction model with current risk-prediction models. RESULTS: Overall, 4216 patients met the inclusion criteria and 3363 completed follow-up. One-, 3-, and 5-year RFS was 94.6% (95% confidence interval [CI] 93.8-95.4), 85.9% (95% CI 84.7-87.1), and 78.8% (95% CI 77.0-80.6), respectively. Sex, tumor location, size, mitotic count, and rupture were independent prognostic factors. A new prognostic index (PI) was developed: PI = 0.000 (if female) + 0.270 (if male) + 0.000 (if gastric GIST) + 0.350 (if non-gastric GIST) + 0.000 (if no tumor rupture) + 1.259 (if tumor rupture) + 0.000 (tumor mitotic count < 6 per 50 high-power fields [HPFs]) + 1.442 (tumor mitotic count between 6 and 10 per 50 HPFs) + 2.026 (tumor mitotic count > 10 per 50 HPFs) + 0.096 × tumor size (cm). Model-predicted 1-, 3-, and 5-year RFS was S(12, X) = 0.9926exp(PI), S(36, X) = 0.9739exp(PI) and S(60, X) = 0.9471exp(PI), respectively. CONCLUSIONS: Sex, tumor location, size, mitotic count, and rupture were independently prognostic for GIST recurrence. Our RFS prediction model is effective for Chinese GIST patients.

Macrophage Colony-stimulating Factor Mediates the Recruitment of Macrophages in Triple negative Breast Cancer.

Triple negative breast cancer (TNBC) is characterized by aggressive malignant tumor, poor prognosis and lack of targeted treatment. Several studies have established that macrophages are closely associated with the progression of TNBC. Through immunohistochemical analysis, we found that the infiltration of macrophage in TNBC tissue was more than that in non-triple negative breast cancer (nTNBC) tissue. Furthermore, the conditioned medium (CM) of MDA-MB-231 and HCC1937, the TNBC cell lines, had significant migration-promoted effect on macrophages. However, the macrophages migration-promoted ability of nTNBC cell line MCF-7 was weaker than that of MDA-MB-231 and HCC1937 cells. Mechanistically, MDA-MB-231 and HCC1937 cells secreted more macrophage colony-stimulating factor (M-CSF) than MCF-7, which is the main inducer of macrophage migration, and the secreted M-CSF promoted the increase in actin and the elongation of pseudopodia. When M-CSF was neutralized by antibody, the elongation of macrophage pseudopodia was disappeared and the migration was inhibited. In vivo, there were more macrophages in tumors induced by MDA-MB-231 than MCF-7 did. Therefore, M-CSF specially secreted by TNBC was the important cause of macrophages aggregation in TNBC, which further promoted the aggressiveness of TNBC.