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Long noncoding RNAs (lncRNAs) refers to a class of RNAs that have at least 200 nucleotides and do not encode proteins, and the relationship between lncRNA and cancer has recently attracted considerable research attention. The lncRNA FGD5-AS1 is a newly discovered lncRNA with a length of 3772 nucleotides. Studies have found that FGD5-AS1 is abnormally highly expressed in many cancer tissues and was closely related to the lymph node metastasis, tumor invasion, survival time, and recurrence rate of various cancers. Mechanistic analyses show that FGD5-AS1 can stabilize mRNA expression by sponging miRNA, which not only induces cancer cell proliferation, metastasis, invasion, and chemoresistance in vitro, but also promotes tumor growth and metastasis in vivo. In addition, FGD5-AS1 can serve as a diagnostic or prognostic marker for a variety of cancers. This review demonstrates the clinical significance of FGD5-AS1 in human cancer and its role in tumorigenesis and tumor progression.

Hemolymphangioma is an extremely rare type of lymphatic and vascular malformation, histologically comprised of both cystic dilated veins and lymphatic vessels. They have been reported to occur in the skin, extremities, pancreas, spleen, mediastinum, as well as in the gastrointestinal tract. A 61-year-old male patient presented with a 2-week history of left lower abdominal and back pain. He had no relevant personal or family past medical history. He denied fever, trauma or weight change, but had noted early satiety with eating. On physical examination, a 10 cm soft, mobile, well-defined, minimally tender mass was palpated in the lower left abdomen. Computed tomography confirmed a large intraperitoneal cystic mass, and resection was advised. The mass was completely excised laparoscopically from the transverse mesocolon. Histopathology verified the diagnosis of hemolymphangioma. The patient recovered uneventfully, and no recurrence was identified at 3 months follow-up. Hemolymphangioma is more common in women and occurs in the fourth to fifth decades of life. The intent of this case report and literature review was to highlight the key aspects of presentation, organ involvement, imaging, histopathological characteristics, and treatment of hemolymphangioma involving the gastrointestinal tract.

The diffuse-type gastric cancer (DGC) is a subtype of gastric cancer (GC) associated with low HER2 positivity rate and insensitivity to chemotherapy and immune checkpoint inhibitors. Here, we identify urokinase-type plasminogen activator receptor (uPAR) as a potential therapeutic target for DGC. We have developed a novel anti-uPAR monoclonal antibody, which targets the domains II and III of uPAR and blocks the binding of urokinase-type plasminogen activator to uPAR. We show that the combination of anti-uPAR and anti–Programmed cell death protein 1 (PD-1) remarkably inhibits tumor growth and prolongs survival via multiple mechanisms, using cell line–derived xenograft and patient-derived xenograft mouse models. Furthermore, uPAR chimeric antigen receptor–expressing T cells based on the novel anti-uPAR effectively kill DGC patient–derived organoids and exhibit impressive survival benefit in the established mouse models, especially when combined with PD-1 blockade therapy. Our study provides a new possibility of DGC treatment by targeting uPAR in a unique manner.

Gastric cancer (GC) is a kind of global malignancy. However, the expression pattern and clinical relevance of lamin B1 in GC remain to be elucidated. We endeavored to investigate how GC is influenced by lamin B1 and the related mechanisms. The lamin B1 expression in GC tissues from 71 patients was assessed by using immunohistochemistry (IHC). The expression of lamin B1 was connected with the clinical stage, depth of invasion, and poorer overall survival. Colony formation assays and methyl thiazolyl tetrazolium (MTT) were used to assess cell viability. The migration ability of GC cells was determined by cell scratch assay and Transwell invasion assay. Moreover, we used two cell lines of GC to explore the underlying mechanism of lamin B1 in boosting the GC cells proliferation and invasion in vitro by assessing the effects on related signal transduction pathways. Our data demonstrated that the expression level of lamin B1 was downregulated in GC tissues, and low expression level of lamin B1 was significantly correlated with higher clinical stage, depth of invasion, nodal stage, and poor prognosis. Moreover, in vitro experiments demonstrated that lamin B1 knockdown promoted, whereas lamin B1 overexpression inhibited, gastric cancer cell proliferation and migration. We also observed that lamin B1 knockdown could promote the activity of the PI3K/PTEN/Akt and MAPK/ERK pathway with a decrease in the p53/p21WAF1/CIP1 expression, whereas lamin B1 overexpression contributed to the opposite results. In conclusion, our studies indicate that lamin B1 deficiency is crucial in GC progression. Furthermore, the results elucidating the biological mechanisms of lamin B1 may potentially contribute to current GC treatment modalities.

Dysregulation of the Wnt/β-catenin signaling pathway is critically involved in gastric cancer (GC) progression. However, current Wnt pathway inhibitors being studied in preclinical or clinical settings for other cancers such as colorectal and pancreatic cancers are either too cytotoxic or insufficiently efficacious for GC. Thus, we screened new potent targets from β-catenin destruction complex associated with GC progression from clinical samples, and found that scaffolding protein RACK1 deficiency plays a significant role in GC progression, but not APC, AXIN, and GSK3β. Then, we identified its upstream regulator UBE2T which promotes GC progression via hyperactivating the Wnt/β-catenin signaling pathway through the ubiquitination and degradation of RACK1 at the lysine K172, K225, and K257 residues independent of an E3 ligase. Indeed, UBE2T protein level is negatively associated with prognosis in GC patients, suggesting that UBE2T is a promising target for GC therapy. Furthermore, we identified a novel UBE2T inhibitor, M435-1279, and suggested that M435-1279 acts inhibit the Wnt/β-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1, resulting in suppression of GC progression with lower cytotoxicity in the meantime. Overall, we found that increased UBE2T levels promote GC progression via the ubiquitination of RACK1 and identified a novel potent inhibitor providing a balance between growth inhibition and cytotoxicity as well, which offer a new opportunity for the specific GC patients with aberrant Wnt/β-catenin signaling.

Background: Epidermal Growth Factor Receptor (EGFR) and members of its homologous protein family mediate transmembrane signal transduction by binding to a specific ligand, which leads to regulated cell growth, differentiation, proliferation and metastasis. With the development and application of Genetically Engineered Antibodies (GEAs), Nanobodies (Nbs) constitute a new research hot spot in many diseases. A Nb is characterized by its low molecular weight, deep tissue penetration, good solubility and high antigen-binding affinity, the anti-EGFR Nbs are of significance for the diagnosis and treatment of EGFR-positive tumours. Objective: This review aims to provide a comprehensive overview of the information about the molecular structure of EGFR and its transmembrane signal transduction mechanism, and discuss the anti-EGFR-Nbs influence on the diagnosis and treatment of solid tumours. Methods: Data were obtained from PubMed, Embase and Web of Science. All patents are searched from the following websites: the World Intellectual Property Organization (WIPO®), the United States Patent Trademark Office (USPTO®) and Google Patents. Results: EGFR is a key target for regulating transmembrane signaling. The anti-EGFR-Nbs for targeted drugs could effectively improve the diagnosis and treatment of solid tumours. Conclusion: EGFR plays a role in transmembrane signal transduction. The Nbs, especially anti- EGFR-Nbs, have shown effectiveness in the diagnosis and treatment of solid tumours. How to increase the affinity of Nb and reduce its immunogenicity remain a great challenge.

Primary synovial sarcoma of the duodenal bulb is a rare mesenchymal tumor with special morphological features. It usually originates from the major joints or tendon sheaths of the extremities and mostly seen in young population, but rarely found in gastrointestinal tract. In this manuscript, we reported the first case of synovial sarcoma arising between the intestinal wall of the duodenal bulb with a concomitant SYT/SSX type of the t(X;18) translocation. A 49-year-old male presented to our hospital with a 2-month history of upper abdominal pain along with a 4-day amply jaundice. Tumor marker testing showed only a slight increase of carbohydrate antigen 19-9 (CA19-9). A computed tomography scan of his abdomen showed that indeterminate tissue occupied the duodenal bulb wall, compressed the surrounding tissues, and measured roughly 5.0 cm × 7.7 cm × 8.7 cm. Since the sarcoma grows between the intestinal wall, which cannot be detected by endoscopy, an initial diagnosis of duodenal wall stromal tumor was made at that time. Postoperative Immunohistochemistry results showed that the tumor was positive for the expression of transducin-like enhancer of split 1, B-cell lymphoma 2, and Vimentin. These pathological findings were indicative of the diagnosis of synovial sarcoma, but still did not provide sufficient diagnostic evidence. Finally we confirmed the diagnosis by using fluorescence in situ hybridization (FISH) with detection of the t(X;18) (SYT-SSX) translocation. No such lesions were found on preoperative examination, so a diagnosis of primary duodenal synovial sarcoma was made. After literature review, we found four reports of duodenal synovial sarcomas, all of which could be detected endoscopically, but there were no results of long-term follow-up. This case is the first reported case of synovial sarcoma arising between the intestinal walls of the duodenal bulb treated twice with ifosfamide and followed up for 13 months without recurrence.

Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. The molecular mechanisms underlying the progression of gastric cancer are still not fully elucidated. In this study, we focused on exploring the role of family with sequence similarity 83, member D (FAM83D) in gastric cancer progression.The expression of FAM83D in GC tissues was detected by immunohistochemistry (IHC) staining. FAM83D knockdown or overexpression were constructed in AGS and SGC-7901 cells with two distinct siRNA duplexes and lentivirus infection, respectively, to explore the role of FAM83D in gastric cancer progression. Nude mouse xenograft assay was used to further explore the role of FAM83D in tumorigenesis in vivo.We found that FAM83D mRNA and protein levels were higher in human GC tumor tissues and in GC cell lines, compared with the adjacent normal tissues and non-malignant gastric epithelial cell lines, respectively, and that higher FAM83D expression was correlated with worse overall survival (This study suggested that FAM83D overexpression enhanced the proliferation, clonogenicity, and motility of GC cells by activating Wnt/β-catenin signaling, and FAM83D may be a promising diagnostic and therapeutic target for human GC.

The mechanism underlying the poor prognosis of gastric cancer, including its high degree of malignancy, invasion, and metastasis, is extremely complicated. Rho GTPases are involved in the occurrence and development of a variety of malignant tumors. ARHGAP11A, in the Rho GTPase activating protein family, is highly expressed in gastric cancer, but its function and mechanism have not yet been explored. In this study, the effect of ARHGAP11A on the occurrence and development of gastric cancer and the mechanism related to this effect were studied. The expression of ARHGAP11A was increased in gastric cancer cells and tissues, and high ARHGAP11A expression in tissues was related to the degree of tumor differentiation and poor prognosis. Moreover, ARHGAP11A knockout significantly inhibited cell proliferation, cell migration, and invasion in vitro and significantly inhibited the tumorigenic ability of gastric cancer cells in nude mice in vivo. Further studies revealed that ARHGAP11A promotes the malignant progression of gastric cancer cells by interacting with TPM1 to affect cell migration and invasion and the stability of actin filaments. These results suggest that ARHGAP11A plays an important role in gastric cancer and may become a useful prognostic biomarker and therapeutic target for gastric cancer patients.

Trastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Released SHCBP1 responds to HER2 cascade by translocating into the nucleus following Ser273 phosphorylation, and then contributing to cell mitosis regulation through binding with PLK1 to promote the phosphorylation of the mitotic interactor MISP. Meanwhile, Shc1 is recruited to HER2 for MAPK or PI3K pathways activation. Also, clinical evidence shows that increased SHCBP1 prognosticates a poor response of patients to trastuzumab therapy. Theaflavine-3, 3’-digallate (TFBG) is identified as an inhibitor of the SHCBP1-PLK1 interaction, which is a potential trastuzumab sensitizing agent and, in combination with trastuzumab, is highly efficacious in suppressing HER2-positive gastric cancer growth. These findings suggest an aberrant mitotic HER2-SHCBP1-PLK1 axis underlies trastuzumab sensitivity and offer a new strategy to combat gastric cancer., Resistance to Trastuzumab in HER2 gastric cancer patients remains a clinical challenge. In this study, the authors demonstrate that HER2 promotes tumorigenesis in gastric cancer by regulating mitotic progression through a Shc1-SHCBP1-PLK1-MISP axis and they identify a compound, TFBG, able to disrupt SHCBP1/PLK1 interaction and to synergize with trastuzumab.

Changes in nuclear morphology are common in malignant tumors, but the underlying molecular mechanisms remain poorly understood. Lamins is involved in supporting nuclear structure, and the expression of Lamins is the molecular basis for nuclear morphological changes during tumor progression. In recent years, the research on the relationship between Lamins and malignant tumors has made great progress. Lamins is of great value in the diagnosis, treatment, and prognosis of various malignant tumors.细胞核形态的变化在恶性肿瘤中普遍存在，但对其潜在的分子机制及作用仍知之甚少。核纤层蛋白参与支撑核结构，其表达的改变是肿瘤进展期间核形态改变的分子基础。近年来有关核纤层蛋白与恶性肿瘤关系的研究取得了较大进展，核纤层蛋白对多种恶性肿瘤的诊断、治疗及预后有重要价值。.

Objective: To evaluate the survival benefit of metformin use for pancreatic cancer (PC) patients underwent pancreatectomy. Methods: Databases including EMBASE, PubMed, the Cochrane Library were searched to identify studies relevant to the outcomes on the survival benefit of metformin use for the PC patients who underwent pancreatectomy until June 30, 2019. STATA 12.0 software was used to performed the meta-analysis. Results: 12 studies involving 35,346 PC patients were included in this meta-analysis. With a random-model, there are significant differences in overall survival (HR = 0.85, 95% CI: 0.77–0.94, P = 0.002) between PC patients who were treated with metformin underwent pancreatectomy and those who underwent pancreatectomy without metformin use. Subgroup analyses showed Caucasians (HR = 0.903, 95% CI = 0.825–0.940, P = 0.008) and Asian (HR = 0.691, 95% CI = 0.588–0.813, P = 0.001) PC patients have a significantly reduced risk of death for metformin users. Subgroup analyses also showed a survival benefit for PC patients at stage I-II (HR = 0.762, 95% CI = 0.677–0.858, P = 0.0001). Conclusions: Metformin use is related to a better survival benefit for PC patients who underwent pancreatectomy, which would be a potential drug for the treatment of PC.

Background Pancreatic fistula is a common complication after pancreaticoduodenectomy, which could be caused by: soft pancreatic tissue, pancreatic duct diameter 2. Here we report a case of pancreatic fistula due to obstruction of the jejunal loop due to compression of the jejunal loop by the superior mesenteric vessels. Case presentation A 68-year-old man was admitted to our ward due to intermittent epigastric distension and pain. After various examinations and treatments, he was diagnosed with middle bile duct cancer. Pancreaticoduodenectomy was performed, and pancreaticojejunostomy and hepaticojejunostomy were completed by lifting the jejunal loop from behind the superior mesenteric vessels to the upper region of the colon. On postoperative day 9, the patient developed acute diffuse peritonitis, and on postoperative day 10, the patient underwent a second exploratory laparotomy, during which it was confirmed that the pancreatic fistula was caused by obstruction of the jejunal loop due to compression of the jejunal loop by the superior mesenteric vessels, then the patient recovered and was discharged alive after retrograde drainage in the jejunum. Conclusions The superior mesenteric vessels after pancreaticoduodenal surgery can compress the jejunal loop and cause obstruction leading to serious complications, and it is recommended that general surgeons should avoid lifting the jejunal loop from the posterior aspect of the superior mesenteric vessels to complete the anastomosis.

Background In this study, we aimed to investigate the preoperative serum carcinoembryonic antigen (CEA) in the diagnosis of positive lymph node metastasis (LNM), and to evaluated the relationship between CEA and survival in patients with locally advanced gastric cancer (LAGC). Methods The significance of the preoperative serum CEA level for the diagnose of LAGC and prediction of LNM was determined using the receiver operating characteristic (ROC) curve. The areas under the ROC of CEA were compared with those of other tumor markers or imaging examination including CT and MRI. Logistic regression was utilized to identify the risk factors predicting positive LNM. Independent prognosis factors were evaluated using univariate and multivariate COX regression analyses. Results The ROC curves showed that the AUCs of CEA, CA199, and CA125 for diagnosing LAGC were 0.727, 0.594, and 0.566. When used to predict LNM, the AUC of CEA, CA199 and CA125 were 0.696, 0.531, and 0.588. Logistic regression analysis demonstrated that preoperative serum CEA were significantly associated with positive LNM. On combining imaging examination with CEA, the sensitivity and specificity were 85.3 and 79.4%, respectively, with the AUC equal to 0.853. The combination of CEA and imaging examination preformed the highest levels of AUC and sensitivity for diagnosing LNM, which is significantly higher than using either of them alone. Although patients with abnormal CEA have a poor prognosis, two models of multivariate analysis showed that CEA was not the independent prognosis factor for survival. Conclusions CEA can be used to diagnose gastric cancer and determine whether it has LNM. Moreover, combined with CEA could improve the diagnostic sensitivity of imaging examination for lymph node involvement.

Abstract Macrophages constitute a major component of tumor-infiltrating immune cells. M2 macrophages have been reported to promote tumor progression through promoting tumor angiogenesis and metastasis and regulating T-cell function. Here, we identified a protumorigenic subset of macrophages that constitutively expressed programmed cell death 1 (PD1) and accumulated in advanced-stage gastric cancer (GC). These PD1+ tumor-associated macrophages (TAMs) exhibited an M2-like surface profile, with a significant increase in the expression of CD206, IL-10, and CCL1, and a clear decrease in the expression of MHC class II, CD64, and IL-12 and the ability to phagocytose ovalbumin. Moreover, PD1+ TAMs can suppress CD8+ T-cell function and this immunosuppressive activity can effectively be enhanced upon triggering PD1 signal. GC-derived exosomes effectively educated monocytes to differentiate into PD1+ TAMs with M2 phenotypic and functional characteristics. Together, our results are the first to show that GC-derived exosomes can effectively induce PD1+ TAM generation, and these cells can produce a large number of IL-10, impair CD8+ T-cell function, and thereby create conditions that promote GC progression. Thus, methods in which immunotherapy is combined with targeting PD1+ TAMs and tumor-derived exosomes should be used to restore immune function in GC patients.

Dysregulation of the Wnt/β-catenin signaling pathway is critically involved in gastric cancer (GC) progression. However, current Wnt pathway inhibitors being studied in preclinical or clinical settings for other cancers such as colorectal and pancreatic cancers are either too cytotoxic or insufficiently efficacious for GC. Thus, we screened new potent targets from β-catenin destruction complex associated with GC progression from clinical samples, and found that scaffolding protein RACK1 deficiency plays a significant role in GC progression, but not APC, AXIN, and GSK3β. Then, we identified its upstream regulator UBE2T which promotes GC progression via hyperactivating the Wnt/β-catenin signaling pathway through the ubiquitination and degradation of RACK1 at the lysine K172, K225, and K257 residues independent of an E3 ligase. Indeed, UBE2T protein level is negatively associated with prognosis in GC patients, suggesting that UBE2T is a promising target for GC therapy. Furthermore, we identified a novel UBE2T inhibitor, M435-1279, and suggested that M435-1279 acts inhibit the Wnt/β-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1, resulting in suppression of GC progression with lower cytotoxicity in the meantime. Overall, we found that increased UBE2T levels promote GC progression via the ubiquitination of RACK1 and identified a novel potent inhibitor providing a balance between growth inhibition and cytotoxicity as well, which offer a new opportunity for the specific GC patients with aberrant Wnt/β-catenin signaling.

// Changjiang Luo 1, * , Yunyi Yao 2, * , Zeyuan Yu 1 , Huinian Zhou 1 , Lingyun Guo 1 , Junqiang Zhang 1 , Hongtai Cao 1 , Genyuan Zhang 1 , Yumin Li 1 , Zuoyi Jiao 1 1 Department of General Surgery, Lanzhou University Second Hospital and Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu, 730030, China 2 Department of Medical Technology and Key Laboratory of Biotechnology for Laboratory Medicine of Suzhou, Suzhou Vocational Health College, Suzhou, Jiangsu, 215009, China * These authors contributed equally to this work Correspondence to: Zuoyi Jiao, email: jiaozy@lzu.edu.cn Yumin Li, email: liym@lzu.edu.cn Keywords: UBE2T, ubiquitination, gastric cancer, tumor apoptosis, invasion and metastasis Received: October 28, 2016 Accepted: February 22, 2017 Published: March 06, 2017 ABSTRACT Ubiquitin-conjugating enzymes (E2 enzymes) such as UBE2T target proteins for degradation via the proteasome. Here, we examined the effects of UBE2T on the progression of gastric cancer. UBE2T was highly expressed in gastric tumors and gastric cancer cells. siRNA-mediated suppression of UBE2T inhibited gastric cancer cell proliferation and colony formation by promoting cell cycle arrest at G2/M phase and increasing apoptosis. Suppression of UBE2T also attenuated the invasive and metastatic abilities of gastric cancer cells by altering expression of epithelial-mesenchymal transition (EMT)-related factors. A xenograft model in which nude mice were injected with UBE2T knockdown human gastric cancer cells confirmed that suppression of UBE2T also decreased tumor formation and growth in vivo . Expression levels of CCND1, Phospho-GSK3B, WNT family members, and MYC were all affected by UBE2T knockdown. These results suggest that UBE2T plays a critical role in gastric cancer, and that it may serve as a useful prognostic biomarker and therapeutic target in gastric cancer patients.

As an important regulator of neddylation, neural precursor cell expressed developmentally downregulated 8 (Nedd8)‑conjugating enzyme E2M (UBE2M) mediates cullin neddylation. Upregulation of the neddylation pathway is associated with tumor progression in intrahepatic cholangiocarcinoma (ICC). The present study was designed to assess the effects of Nedd8‑conjugating enzyme UBE2M knockdown on intrahepatic cholangiocarcinoma cells, and to determine the potential underlying mechanisms. UBE2M and associated protein expression levels were determined via immunohistochemistry and western blotting. ICC cells were transfected with short hairpin RNA to knockdown UBE2M expression. Cell Counting Kit‑8 and colony formation assays, and xenograft experiments were used to examine cell viability and colony survival in vitro, and tumor formation in vivo. Survival was evaluated using Kaplan‑Meier analysis and log‑rank tests. Patients with ICC presenting high expression of UBE2M exhibited worse accumulative recurrence and overall survival compared with patients with low expression. Knockdown of UBE2M expression led to a decrease in the viability and clonogenic survival of QBC939 and HUCCT1 cells, and suppressed tumor formation in vivo. UBE2M silencing caused accumulation of cullin‑RING ligase substrates (chromatin‑licensing and DNA replication factor 1 and origin recognition complex subunit 1), inducing DNA damage responses and apoptosis. The present findings suggested that UBE2M serves an important role in ICC progression and may present as a novel target for the treatment of ICC.

Background Although the preoperative immune status is associated with the prognosis in some tumors, less is known about the prognostic significance of immune status change during the treatment of patients with locally advanced gastric cancer (LAGC).Methods The records of 210 patients with LAGC were retrospectively analysed. The pre-, and post-treatment (after gastrectomy and three cycles of chemotherapy) values of lymphocyte-to-monocyte ratio (LMR) and change of LMR (cLMR) were evaluated. A novel immunity change score (ICS) incorporated both preoperative LMR (pLMR) and cLMR was developed and its prognostic value was evaluated.Results cLMR was an independent predictor and patients with cLMR >1 after treatment had a favorable survival compared with the others (51 vs 31 months, P < 0.001). Based on the cLMR and pLMR, the ICS was defined as follows: ICS=1 (pLMR≤4.53 and cLMR≤1); ICS=2 (pLMR≤4.53 and cLMR>1, or pLMR>4.53 and cLMR≤1); and ICS=3 (pLMR>4.53 and cLMR>1). Multivariate analysis revealed that the ICS was a significant independent biomarker ( P < 0.001). The performances of ICS in terms of the time-dependent receiver operating characteristics (t-ROC) curve and concordance index (C-index) analysis were better than those of pLMR and cLMR. Then we established a nomogram incorporated the ICS, CEA, and TNM stage to predict the 3- and 5- year survival. Decision curve analysis and calibration curve demonstrated that the nomogram was clinically useful.Conclusion The dynamic change of immune status is significantly associated with prognosis for LAGC patients. Combining with the cLMR and pLMR could improve the prognostication for LAGC patients.

Cell migration and invasion play an important role in the development of cancer. Cell migration is associated with several specific actin filament-based structures, including lamellipodia, filopodia, invadopodia and blebs, and with cell-cell adhesion, cell-extracellular matrix adhesion. Migration occurs via different modes, human epithelial cancer cells mainly migrate collectively, while in vivo imaging studies in laboratory animals have found that most cells migrate as single cells. Rho GTPases play an important role in the process of cell migration, and several Rho GTPase-related signaling complexes are also involved. However, the exact mechanism by which these signaling complexes act remains unclear. This paper reviews how Rho GTPases and related signaling complexes interact with other proteins, how their expression is regulated, how tumor microenvironment-related factors play a role in invasion and metastasis, and the mechanism of these complex signaling networks in cell migration and invasion.

Superior mesenteric artery (SMA) first approach was a new improvement for pancreaticoduodenectomy (PD), but there is no evidence whether this approach is advantageous to PD. This meta-analysis aimed to determine the effects of the superior mesenteric artery (SMA) first approach on outcomes of pancreaticoduodenectomy (PD).Literature searches were conducted on PubMed, The Cochrane Library, EMBASE, Web of Science, Clinical Trials Registry and China Biology Medicine disc. We completed a meta-analysis of the SMA first approach in PD, assessing overall survival, R0 resection, blood loss, postoperative complications, operation time and postoperative stay. The odds ratios and weighted mean differences with 95% confidence intervals (CIs) were pooled.Eighteen studies comprising 1483 participants were included. Patients who received SMA-PD had significantly lower overall complication rate (OR 0.62, 95% CI 0.47 to 0.81, P = 0.001) and less blood loss (WMD -264.84, 95% CI -336.1 to -193.58, P 0.001). The obviously increased R0 resection rate (OR 2.92, 95% CI 1.72 to 4.96, P 0.001) and 3-year OS (OR 2.15, 95% CI 1.34 to 3.43, P = 0.001) were found in the SMA-PD group.The SMA-PD group had better clinical outcomes, particularly in long-term survival of pancreatic cancer patients; furthermore, the patients acquired superior clinical efficacy via the posterior approach in SMA-PD.

Gastric cancer (GC) is one of the most frequently diagnosed digestive malignancies and is the third leading cause of cancer‑associated death worldwide. Delayed diagnosis and poor prognosis indicate the urgent need for new therapeutic strategies. The success of chimeric antigen receptor (CAR) T‑cell therapy for chemotherapy‑refractory hematological malignancies has inspired the development of a similar strategy for GC treatment. Although using CAR T‑cells against GC is not without difficulty, results from preclinical studies remain encouraging. The current review summarizes relevant preclinical studies and ongoing clinical trials for the use of CAR T‑cells for GC treatment and investigates possible toxicities, as well as current clinical experiences and emerging approaches. With a deeper understanding of the tumor microenvironment, novel target epitopes and scientific‑technical progress, the potential of CAR T‑cell therapy for GC is anticipated in the near future.

Furong Wang,1,2,* Sigong Zhang,2,3,* Yucai Wei,2,4 Hao Chen,2,4Zuoyi Jiao,2,4Yumin Li2,41Department of Pathology, The Second Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of China; 2The Key Laboratory of the Digestive System Tumors of Gansu Province, The Second Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of China; 3Department of Rheumatology, The Second Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of China; 4Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou 730000, People’s Republic of China*These authors contributed equally to this workBackground/aims: Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. The molecular mechanisms underlying the progression of gastric cancer are still not fully elucidated. In this study, we focused on exploring the role of family with sequence similarity 83, member D (FAM83D) in gastric cancer progression.Methods: The expression of FAM83D in GC tissues was detected by immunohistochemistry (IHC) staining. FAM83D knockdown or overexpression were constructed in AGS and SGC-7901 cells with two distinct siRNA duplexes and lentivirus infection, respectively, to explore the role of FAM83D in gastric cancer progression. Nude mouse xenograft assay was used to further explore the role of FAM83D in tumorigenesis in vivo.Results: We found that FAM83D mRNA and protein levels were higher in human GC tumor tissues and in GC cell lines, compared with the adjacent normal tissues and non-malignant gastric epithelial cell lines, respectively, and that higher FAM83D expression was correlated with worse overall survival (p

Gastric neuroendocrine tumors are rarely seen in the gastric tumors, because there are few case reports and the clinical diagnosis rate is low. There is no consensus treatment method in the world. However, with the benefit of esophagogastrodenoscopy and widespread use of proton pump inhibitors, the diagnostic rate of gastric neuroendocrine tumors is on the increase, which gives us an updated understanding for the pathogenesis and pathophysiology of the disease. By studying its pathogenesis, scholars have found that hypergastrinemia caused by various causes is closely related to its occurrence. Gastric neuroendocrine tumors are classified into different types or pathological grades depending on the state of progression of the disease and the unique clinical manifestations. Clinically used diagnostic methods include gastroscopy, medical imageology, nuclear medicine, gastrin, CgA, etc. There are also differences in treatments depending on the clinical classification. If the disease progresses rapidly and the grade is high, surgical resection of the lesion plus postoperative adjuvant chemotherapy should be actively performed. Other better treatments are still being explored.胃神经内分泌肿瘤是临床较少见的一类肿瘤性病变，由于病例报道少，临床诊断率较低，在国内外尚无统一的诊疗方法。得益于内镜技术的发展以及临床上广泛应用的质子泵抑制剂，胃神经内分泌肿瘤的发病率和诊断率呈现上升的趋势。通过研究其发病机制，学者发现其发生与各种原因引起的高胃泌素血症密切相关。根据疾病的进展状态和临床表现，学者对胃神经内分泌肿瘤进行了分型和病理分级。临床上运用的诊断方法有胃镜、影像学、核医学、胃泌素、CgA等检查。根据临床分型的不同，治疗手段也存在差异，如果疾病进展迅速且分级较高，则应积极行外科手术切除病灶加术后辅助化学药物治疗。其他更好的治疗方法还在不断探索中。.

The primary cilium, a sensory organelle that emanates from the cell surface of most mammalian cell types during growth arrest, has attracted the attention of many researchers over the past decade. Recently, a large number of new findings have assigned novel functions and roles to the primary cilium in signal transduction and related diseases, which has greatly augmented the importance of the cilium in human health and development. Here, we review emerging evidence supporting the primary cilium as a sensory organelle in signal transduction in microgravity, electromagnetic field sensing, chemosensation and tumorigenesis. We also present an overview of signal transduction crosstalk associated with the primary cilium in bone disease and cancer, including primary cilium-related Ca2+ signaling, parathyroid hormone signaling, cAMP signaling, BMP/Smad1/5/8 signaling and Wnt signaling. We anticipate that emerging discoveries about the function of the primary cilium will provide novel insight into the molecular mechanisms of stimulus sensation, signal transduction and pathogenesis.

Src homolog and collagen homolog (Shc) proteins have been identified as adapter proteins associated with cell surface receptors and have been shown to play important roles in signaling and disease. Shcbp1 acts as a Shc SH2-domain binding protein 1 and is involved in the regulation of signaling pathways, such as FGF, NF-κB, MAPK/ERK, PI3K/AKT, TGF-β1/Smad and β -catenin signaling. Shcbp1 participates in T cell development, the regulation of downstream signal transduction pathways, and cytokinesis during mitosis and meiosis. In addition, Shcbp1 has been demonstrated to correlate with Burkitt-like lymphoma, breast cancer, lung cancer, gliomas, synovial sarcoma, human hepatocellular carcinoma and other diseases. Shcbp1 may play an important role in tumorigenesis and progression. Accordingly, recent studies are reviewed herein to discuss and interpret the role of Shcbp1 in normal cell proliferation and differentiation, tumorigenesis and progression, as well as its interactions with proteins.

Keshen Wang,1 Yanxian Ren,1 Zhijian Ma,2 Fan Li,1 Xiaocheng Cheng,1 Jingying Xiao,1 Shuze Zhang,1 Zeyuan Yu,1 Hanteng Yang,1 Huinian Zhou,1,2 Yuming Li,1,2 Hongbin Liu,3 Zuo-Yi Jiao1,21Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu 730010, People’s Republic of China; 2Cui-ying Experimental Center, Lanzhou University Second Hospital, Lanzhou, Gansu 730010, People’s Republic of China; 3Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of People’s Liberation Army, Lanzhou 730050, People’s Republic of ChinaIntroduction: Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric cancer (LAGC); however, evidence for its use as a standard treatment has not been established in China. The aim of this study was to investigate the effectiveness, safety, and feasibility of the FLOT regimen as neoadjuvant chemotherapy in Chinese patients with resectable LAGC.Methods: We conducted an observational study to compare the effectiveness of FLOT regimen consisting of docetaxel (60 mg/m2,), oxaliplatin (85 mg/m2,), leucovorin (200 mg/m2,), and 5-fluorouracil (2,600 mg/m2, as a 24 hr infusion), all given on day 1 and administered every 2 weeks versus initial surgery followed by chemotherapy in patients with clinical T3–4 LAGC. OS was compared by using the Cox proportional hazards regression model and the Kaplan–Meier curve adjusted by inverse probability of treatment weighting (IPTW) and propensity score-matched (PSM) analysis. In addition, we performed subgroup analyses to determine the effectiveness of the FLOT regimen in clinically relevant patient subsets.Results: Overall, 47 patients who received initial FLOT chemotherapy and 269 patients who received initial surgery were enrolled in this study. In the PSM analysis, the FLOT-first group showed favorable OS compared with the surgery-first group (41 vs 41 [HR, 0.416; 95% CI, 0.218–0.794; P=0.008]), and 3-year survival rates were 58.7% and 30.9% in the FLOT-first group and surgery-first group, respectively. IPTW analysis showed similar results. However, the effect of FLOT was low (HR, 0.868; 95 CI%, 0.215–3.504) in patients without lymph node metastasis.Conclusion: Our study suggests that preoperative FLOT chemotherapy is safe and feasible. In terms of OS, FLOT may be superior to initial surgery followed by chemotherapy in reducing morbidity with resectable LAGC.Keywords: gastric cancer, preoperative chemotherapy, propensity score, FLOT, prognosis

Background: National Comprehensive Cancer Network (NCCN) guidelines recommend surgery, chemotherapy, and radiation therapy for gastric cancer patients. Neoadjuvant treatments as the administration of therapeutic agents before a main treatment gained in more and more attention. However, the role of neoadjuvant treatments is still controversial. The main aim of this systematic review and network meta-analysis is to assess the relative efficacy of different neoadjuvant treatment regimens for gastric cancer using network meta-analysis method. Methods: We will search 5 electronic databases to identify randomized controlled trials (RCTs) and non-RCTs compared the efficacy differences of surgery alone (S), preoperative chemotherapy follow by surgery (CTS), preoperative radiotherapy follow by surgery (RTS), and preoperative chemoradiotherapy follow by surgery (CRTS) for patients with gastric cancer. The risk of bias tool from the Cochrane Handbook version 5.1.0 will be used to assess the risk of bias of RCTs, and the risk of bias in nonrandomized studies of interventions (ROBINS-I) for non-RCTs. Data will be analyzed using R-3.4.1 software. Results and conclusion: The results of present network meta-analysis will estimate the relative efficacy among all interventions and rank the interventions even if head-to-head comparisons are lacking and will provide more evidence for clinicians, researchers, and patients in the management of gastric cancer. Protocol registration number: CRD42017074956

Gastric cancer is one of the most common malignant gastrointestinal tumors. Docetaxel alone or combination with other drugs can attenuate the progress of disease, prolong the overall response rate and the median overall survival rate in advanced gastric cancer. However, the incidence of toxicities is high. Moreover, there is no uniform standard for dosage and course for docetaxel treatment. Currently, its efficacy is not definite.胃癌是最常见的消化系统恶性肿瘤之一，多西他赛单药及联合用药可在进展期胃癌中缓解疾病进展，延长患者中位生存时间。不同的化学治疗方案中，多西他赛的剂量和疗程尚无统一标准，不良反应发生率各异，目前疗效尚未完全确定。.

To explore the relationships between the expression level of different galectins and its prognostic value for patients with gastric cancer.The PubMed, EMbase, the Cochrane Library and Web of Science databases were systematically searched. All the eligible studies were included according to the inclusion and exclusion criteria. All the relevant data was extracted by two independent researchers. The quality assessment was conducted according to the evaluation of the quality of prognosis study which published by Harden in 2006. The STATA 12.0 software was used to perform a meta-analysis.All of 8 retrospective case-controlled studies involving 2093 patients with gastric cancer were included in this study. The results of meta-analysis presented that the elevated galectin-1 which is related to the poor overall survival (HR = 1.85, 95% CI: 1.33-2.58; P 0.001) may predicted a larger tumor size (OR = 2.20, 95% CI: 1.35-3.35; P = 0.001) and was positively associated with the higher expression of VEGF (OR = 1.44, 95% CI: 1.14-1.82; P = 0.002). Moreover, the decreased galectin-3 (HR = 0.49, 95% CI: 0.36-0.67; P 0.001), galectin-8 (HR = 0.49, 95% CI: 0.36-0.67; P 0.001) and galectin-9 (HR = 0.78, 95% CI: 0.66-0.92; P = 0.003) were also significantly associated with poorer prognosis. Our meta-analysis also showed that lower expression of galectin-3 was also related to lymphatic vessel invasion (OR = 0.48, 95% CI: 0.26-0.89; P = 0.018), worse TNM stages (OR = 0.47, 95% CI: 0.32-0.40; P 0.001), deeper invasive depth (OR = 0.33, 95% CI: 0.21-0.51; P 0.001) and poorer differentiation grade (OR = 0.10, 95% CI: 0.04-0.25; P 0.001).High expression of galectin-1 or low expression of galectin-3, -8 and -9 were significantly related to a poorer prognosis for patients with gastric cancer. The expression level of galectins was associated with clinical characteristics and were potential independent prognostic predictor for GC patients.

Macrophages constitute a major component of tumor-infiltrating immune cells. M2 macrophages have been reported to promote tumor progression through promoting tumor angiogenesis and metastasis and regulating T-cell function. Here, we identified a protumorigenic subset of macrophages that constitutively expressed programmed cell death 1 (PD1) and accumulated in advanced-stage gastric cancer (GC). These PD1

Pancreatic cancer is a highly lethal disease in gastrointestinal malignant tumors. The mortality of pancreatic cancer closely parallels its incidence. Most patients with pancreatic cancer remain asymptomatic until the disease reaches an advanced stage. There is no program for screening patients at high risk of pancreatic cancer. Although CT, MRI, positron emission tomography, endoscopic ultrasonography, and endoscopic ultrasonography-guided fine-needle aspiration offer high diagnostic ability for pancreatic cancer, it cannot be found at the early stage easily. Surgical resection is regarded as the only potentially curative treatment and adjuvant chemotherapy is given after surgery. This article reviews epidemiology, risk factors, diagnosis and treatment for pancreatic cancer by summarizing relevant literature.胰腺癌是恶性程度极高的消化道肿瘤，其病死率与发病率接近，早期症状较隐匿，诊断时大多已是晚期。目前尚无胰腺癌早期高风险因素筛查的标准，虽然CT，MRI，正电子发射断层显像/CT，超声内镜及超声内镜引导下的细针穿刺均用于胰腺癌的诊断，但早期诊断仍困难。手术切除是唯一可根治的治疗方式，但术后预后差；术后化疗方案在不断更新。.

To explore the prognosis and surgical method for diffuse-type advanced gastric cancer (AGC). The clinicopathological data of patient, who underwent curative gastrectomy in the Second Hospital Affiliated to Lanzhou University from 2005 to 2010, were analyzed retrospectively. The prognostic factors of diffuse-type AGC were analyzed by Cox regression models. The patients were divided into a total gastrectomy group (n=120) and a subtotal gastrectomy group (n=167) according to the surgical approach. Survival rates were established by the Kaplan-Meier method and compared by the Log-rank test between the total gastrectomy group and the subtotal gastrectomy group. A total of 287 patients with diffuse-type AGC were enrolled in this study, including 120 patients in the total gastrectomy group and 167 patients in the subtotal gastrectomy group. Univariate analysis showed that the prognosis of diffuse-type AGC was associated with body mass index, number of retrieved lymph nodes, Borrmann type, tumor size, T stage, N stage, tumor-node-metastasis (TNM) stage, extent of resection, surgical margin, postoperative complication, perineural and vascular invasion (all P0.01). Multivariate analysis showed that normal body mass index, tumor size, T stage, N stage, total gastrectomy, surgical margin, postoperative complication were the independent predictors for diffuse-type AGC (all P0.05). The 5-year overall survival rate and progression-free survival rate for diffuse-type AGC after curative gastrectomy were 17.8% and 13.6%, respectively. The median survival time and progression-free survival of them were 22 and 18 months, respectively. The overall survival rate and progression-free survival rate in the total gastrectomy group was significantly higher than that in the subtotal gastrectomy (P0.01); the extended extent of lymph node dissection, the lower rate of positive surgical margin and postoperative complications were present in the total gastrectomy group (all P0.05 or P0.01). The patients with diffuse-type AGC have a poor prognosis. The great tumor diameter, advanced T stage, advanced N stage, subtotal gastrectomy, high rate of positive surgical margin and postoperative complication are independent risky factors for the diffuse-type AGC. However, the total gastrectomy may be beneficial to patients.目的：探讨弥漫型进展期胃癌(advanced gastric cancer，AGC)的预后及手术方式的选择。方法：回顾性分析2005年至2010年兰州大学第二医院行根治性胃癌切除术的287例AGC患者的临床病理资料，采用Cox回归模型分析弥漫型AGC预后的影响因素。根据手术方式的不同将其分为全胃切除组(n=120)和部分胃切除组(n=167)，采用Kaplan-Meier法计算其生存率，生存率的比较采用Log-rank法检验。结果：单因素分析显示体质量指数、淋巴结切除数、Borrmann分型、肿瘤大小、T分期、N分期、TNM分期、切除范围、手术切缘、神经及脉管浸润、术后并发症均与弥漫型AGC预后相关(均P0.01)；多因素分析显示正常体质量指数、肿瘤大小、T分期、N分期、全胃切除、手术切缘、术后并发症是影响弥漫型AGC预后的独立因素(均P0.05)。弥漫型AGC术后5年总体生存率和无瘤生存率分别为17.8%和13.6%，中位生存期和无瘤生存期分别为22和18个月。相对于部分胃切除组，全胃切除组可提高弥漫型AGC术后总体生存率和无瘤生存率(均P0.01)；全胃切除组具有更广泛的淋巴结清扫范围，较低的切缘阳性率和术后并发症发生率(均P0.05或P0.01)。结论：弥漫型AGC患者预后较差。较大的肿瘤直径、高T分期、高N分期、部分胃切除、高切缘阳性率和术后并发症发生率是其预后不良的独立危险因素，根治性全胃切除术可使患者生存获益。.