Predictive Value of Postoperative C-reactive Protein Ratio for Early Postoperative Complications After Laparoscopic Gastrectomy.

Context: Laparoscopic gastrectomy (LG) provides advantages such as rapid postoperative recovery and little trauma, but postoperative complications are still unavoidable. Detecting serious complications after LG surgery is still a difficult problem for digestive surgeons. Objective: The study intended to evaluate the clinical significance of the C-reactive protein (CRP) ratio in predicting postoperative complications after LG. Design: The research team performed a retrospective analysis. Setting: The study took place at Department of General Surgery, Qingdao Clinical Medical College, Nanjing Medical University, Qingdao, China. Participants: Participants were 128 patients with gastric cancer, confirmed through histopathology, who underwent an LG in the general surgery department of the hospital between January 2015 and January 2020. Groups: Based on the optimal cut-off value of the CRP ratio, the research team divided participants into two groups, with 30 participants with a CRP ratio of >2.0 in the high CRP-value group and 98 with a CRP ratio of ≤2.0 in the low CRP-value group. Also, based on the incidence of complications, the team divided participants into a second set of groups, with 30 participants in a severe complications group and 98 in a nonsevere complications group. Outcome Measures: The research team: (1) determined participants' CRP ratios and compared the clinicopathological characteristics of the high and low CRP-value groups, (2) identified the postoperative complications that participants experienced and compared the clinicopathological characteristics of the severe and nonsevere complications groups, (3) analyzed the predictive value of the CRP levels for early complications after LG using a receiver operating characteristic (ROC) curve, and (4) performed a multivariate regression analysis to determine the risk factors for serious complications. Results: No significant differences existed between the two complication groups in CRP value, white-blood-cell (WBC) count, and WBC count ratio on days 1 and 3 after surgery (P > .05), but the severe complications group had a significantly higher CRP ratio than the nonsevere complications group did (P < .001). The ROC curve showed that the sensitivity, specificity, positive predictive value, and negative predictive value of CRP in predicting severe complications after LG were 67.19%, 84.38%, 73.28%, and 83.27%, respectively. Thank you for your suggestion, we have added tables for these data. Compared to the low CRP-ratio group, the high CRP-value group had: (1) a significantly higher body mass index (BMI), with p=0.031; (2) was significantly more likely to have preoperative underlying diseases (P = .011); (3) was significantly more likely to have had a total gastrectomy (P = .006); (4) was significantly more likely to be in the T3+T4 stage (P = .034); (5) was significantly more likely to be in the tumor, node, metastasis (TNM) stage II or III (P = .010); and (6) was significantly more likely to have had postoperative severe complications (P < .001). The multivariate analysis found that the independent risk factors for severe complications after LG included: (1) preoperative underlying diseases-OR=3.624, 95% CI: (1.191, 11.206) and P = .023; (2) an advanced TNM stage [OR=9.037, 95% CI: (1.729, 47.226), P = .009; and (3) a CRP ratio >2.2 [OR=20.473, 95% CI: (7.948, 52.737), P < .001. Conclusions: The CRP ratio after LG can effectively predict postoperative complications that need treatment, and when the ratio is more than 2.2, digestive surgeons should pay attention to the possibility of serious complications.

Meta­analysis of randomized controlled trials comparing intracorporeal versus extracorporeal anastomosis in minimally invasive right hemicolectomy: upgrading the level of evidence.

BACKGROUND: Minimally invasive right hemicolectomy has been increasingly used for the treatment of right hemicolectomy disease, and both intracorporeal anastomosis (ICA) and extracorporeal anastomosis (ECA) are available to restore intestinal continuity. However, the advantages and disadvantages of these two anastomoses are highly controversial. The present meta-analysis evaluated the effectiveness of ICA versus ECA in minimally invasive right colectomy to improve the grade of evidence. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) comparing intracorporeal versus extracorporeal anastomosis in laparoscopic or robotic right hemicolectomy published from database inception to February 2023. Two researchers performed the literature review, data extraction, bias assessment, and meta-analysis of the data using Review Manager 5.4 software. RESULTS: Seven RCTs with a total of 750 patients were included in the meta-analysis. The results showed a lower incidence of postoperative paralytic ileus (RR 0.62, 95% CI 0.39 ~ 0.99, p = 0.04) and shorter incision length (MD - 1.38; 95% CI: - 1.98 ~ - 0.78, p < 0.00001), but longer operative time (MD 10.69; 95% CI: 2.76 ~ 18.63, p = 0.008). The remaining events including bleeding (RR 0.49, 95% CI: 0.12 ~ 2.04, p = 0.33), anastomotic leak (RR 0.62, 95% CI: 0.39 ~ 0.99, p = 0.85), surgical site infection (RR 0.15, 95% CI: 0.22 ~ 1.25, p = 0.15), overall perioperative morbidity (RR 0.86, 95% CI: 0.58 ~ 1.26, p = 0.44), number of harvested lymph nodes (MD 0.75; 95% CI: - 0.15 ~ 1.65, p = 0.10), and length of hospital stay (MD - 0.27; 95% CI: - 0.91 ~ 0.38, p = 0.42) were not statistically significant. CONCLUSIONS: Compared to ECA, ICA in minimally invasive right hemicolectomy reduced the risk of postoperative paralytic ileus and shortened the length of the incision but prolonged the operative time.

Prognostic Value of Tumor Deposit Counts in Patients with Stage III Colorectal Cancer: A Population-Based Study.

OBJECTIVE: To investigate the prognostic value of tumor deposits (TDs) counts in stage III colorectal cancer (CRC) patients and develop a prognostic nomogram. METHODS: Data on stage III CRC patients from 2010 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier analysis was used to assess differences in survival outcomes among patients. The Cox regression analysis was performed to establish the independent prognostic factors for cancer-specific survival and to establish a nomogram. The nomograms' performance was evaluated by calibration plots and concordance index (C-index). Decision curve analysis (DCA) was used to assess the clinical utility of the prediction model. RESULTS: A total of 23,345 CRC patients were included in this study, and 3,578 (15.3%) had TDs. Cox multivariate regression analyses revealed that age, race, histological tumor grade, the administered chemotherapy, pathological type, T-stage, CEA, N-stage, peripheral nerve invasion, and TDs were independent prognostic factors. Patients with many TDs (=0/1-4, HR: 1.325,/≥5 HR: 2.223) had poorer cancer-specific survival. The prognostic value of the number of TDs was comparable to that of lymph node metastasis. The C-indices of the nomogram were superior to TNM staging in training (0.730 vs 0.646) and validation (0.714 vs 0.636) groups. DCA revealed that the nomogram had a higher clinical net benefit compared to TNM staging. CONCLUSIONS: TDs count is an adverse prognostic factor for stage III CRC patients. Furthermore, the TDs-based nomogram can accurately predict the prognostic outcomes for stage III CRC.

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.

Acute appendicitis caused by metastatic gastric adenocarcinoma: a case report and literature review.

It is rare that Acute appendicitis (AA) caused by metastatic gastric adenocarcinoma is seen in the clinic. The underling mechanism is not clear, and the prognoses of these patients have been discrepant. Herein, we have presented a case of this disease seen in our clinic and summarized 7 similar previously reported cases. We reported the case of a 33-year-old female patient who presented with gastric cancer (GC) metastasis to the appendix that was found incidentally in the emergency surgery for AA with evidence of multi-site metastases. The final pathology of endoscopic biopsy and positron emission tomography-computed tomography (PET-CT) confirmed late-stage GC with multi-site metastases. Chemotherapy and radiotherapy were taken after diagnosed, and the patient died about 7 months after appendicectomy. We also reviewed 7 case-reports on GC metastasis to the appendix. The metastasis was symptomatic in 4 cases, and appendectomy was performed in all cases. The prognosis of the cases varied considerably. There was a total of 8 cases included in this paper. We discussed the diagnosis and the potential route of appendiceal metastasis from GC. Of the 8 cases, 6 had a history of GC. We also examined the prognosis of the cases and the benefit of performing appendectomy in every gastrectomy.

circCCDC66 promotes thyroid cancer cell proliferation, migratory and invasive abilities and glycolysis through the miR-211-5p/PDK4 axis.

Cancer metastasis is the main cause of death in cancer patients, including patients with thyroid cancer (TC). TC is the most common malignant endocrine tumour. In the recent years, increasing evidence has demonstrated that circular RNAs (circRNAs) serve a significant role in the development of many types of human cancer. However, the function and underlying mechanism of circCCDC66 in TC remain unclear. The present study aimed to explore the role of circCCDC66 in TC. To do so, reverse transcription quantitative PCR was used to detect the expression level of circCCDC66. Cell viability, migratory and invasive abilities, and glucose consumption were evaluated by cell counting kit 8, Transwell and glucose consumption assays, respectively. The association between circCCDC66 or pyruvate dehydrogenase kinase 4 (PDK4) and miR-211-5p was verified by dual-luciferase reporter assay. The results demonstrated that circCCDC66 expression was significantly increased in TC tissues and cell lines. Furthermore, silencing circCCDC66 inhibited TC cell proliferation, migratory and invasive abilities and glycolysis in vitro. Further validation demonstrated that circCCDC66 directly interacted with the microRNA (miR) miR-211-5p. Subsequently, the activity of circCCDC66 was attenuated by miR-211-5p. In addition, the results demonstrated that circCCDC66 may promote papillary thyroid cancer progression by sponging miR-211-5p and increasing expression of PDK4. In conclusion, the present study demonstrated that circCCDC66 could promote TC cell proliferation, migratory and invasive abilities and invasion and glycolysis through the miR-211-5p/PDK4 axis. These findings suggested that targeting circCCDC66 may be considered as a promising therapeutic strategy for TC.

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.

Elevated visceral fat area is associated with adverse postoperative outcome of radical colectomy for colon adenocarcinoma patients.

OBJECTIVE: To assess the impact of visceral obesity quantified by preoperative computed tomography on short-term postoperative outcomes compared with body mass index (BMI) in stage I-III colon adenocarcinoma patients. METHODS: In this retrospective study, 107 patients treated with radical colectomy for stage I-III colon adenocarcinoma were classified as obese or non-obese by computed tomography-based measures or BMI (obese: BMI ≥28 kg/m2 , visceral fat area (VFA) to subcutaneous fat area ratio (V/S) ≥0.4, and VFA ≥100 cm2 ). Clinical variables, operation time, estimated blood loss, pathologic stage, histologic grade, postoperative complications, postoperative stay and hospitalization expenses were compared. RESULTS: Obese patients by VFA were more likely to have higher postoperative complication rate (32.9 versus 11.8%, P = 0.021), have longer operation time (184.6 ± 49.5 versus 163.1 ± 44.1 min, P = 0.033), postoperative stay (15.21 ± 7.59 versus 12.29 ± 5.40 days, P = 0.047) and cost more ($10 758.7 ± 3271.7 versus $9232.0 ± 2994.6, P = 0.023) than non-obese. CONCLUSION: Visceral obesity graded by VFA is associated with increased postoperative morbidity, operation time, postoperative stay and hospitalization expenses for colon adenocarcinoma patients and may be superior to BMI or V/S for the prediction of colon surgery.

MicroRNA 495 Inhibits Proliferation and Metastasis and Promotes Apoptosis by Targeting Twist1 in Gastric Cancer Cells.

Recently, microRNAs (miRNAs) have been reported to participate in multiple biological processes. However, the effects of miR-495 on gastric cancer (GC) remain unclear. The purpose of this study was to explore the functions of miR-495 in GC cell proliferation, metastasis, and apoptosis. SGC-7901 and BGC-823 cell lines were transfected with miR-495 mimic, miR-495 inhibitor, and negative controls (mimic control and inhibitor control). The expressions of miR-495, cell viability, migration, apoptosis, and apoptosis-related factors were examined by qRT-PCR, trypan blue staining, Transwell, flow cytometry, and Western blot, respectively. Simultaneously, key factor expression levels of EMT were detected by qRT-PCR and Western blot. The direct target of miR-495 was confirmed by dual-luciferase assay. Additionally, sh-Twist1, pc-Twist1, and corresponding controls were transfected into SGC-7901 and BGC-823 cells, and the protein levels of EMT-associated factors were detected by Western blot. miR-495 was downregulated in GC cells. miR-495 expression level was effectively overexpressed or suppressed in SGC-7901 and BGC-823 cells. Overexpression of miR-495 significantly decreased cell viability and migration, increased apoptosis, and inhibited the EMT process. Suppression of miR-495 showed contrary results. Twist1 was clarified as a target gene of miR-495, and Twist1 silencing obviously reduced the promoting effect of miR-495 suppression on these biological processes. Twist1 silencing significantly blocked the EMT process in both SGC-7901 and BGC-823 cells. miR-495 inhibited proliferation and metastasis and promoted apoptosis by targeting Twist1 in GC cells. These data indicated that miR-495 might be a novel antitumor factor of GC and provide a new method for the treatment of GC.

Expression levels of miR-205 and miR-506 in colon cancer tissues and their relationships with clinicopathological features.

The study intended to investigate the expression levels of micro ribonucleic acid (miR)-205 and miR-506 in colon cancer tissues and their relationships with clinicopathological features. The expression levels of miR-205 and miR-506 in colon cancer tissues and para-carcinoma normal colonic mucosa tissues were detected via fluorescence reverse transcription quantitative polymerase chain reaction (RT-qPCR), and the expression levels of the two miRNAs in plasma of colon cancer patients and healthy control population were also detected. Moreover, the relationships of the two miRNAs with clinicopathological features of patients with colon cancer were analyzed. The expression levels of the two miRNAs in colon cancer tissues were higher than those in para-carcinoma normal colonic mucosa tissues, and also significantly higher in plasma of the colon cancer patients than those in the healthy control population. The differences were statistically significant (P<0.05). The expression level of miR-205 was associated with tumor-node-metastasis (TNM) staging and lymph node metastasis, while the expression level of miR-506 was associated with lymph node metastasis. The differences were statistically significant (P<0.05). The expression levels of miR-205 in the colon cancer tissues and plasma in patients had no significant correlation (r=0.467, P=0.081). There was a positive correlation between the expression levels of miR-506 in the colon cancer tissues and plasma in patients (r=0.599, P=0.038). The expression levels of miR-205 and miR-506 are upregulated in the colon cancer patients, both of which may be closely related to the occurrence and development of colon cancer, and may become potential tumor markers as well as relevant therapeutic targets.

Expression of transmembrane protein 41A is associated with metastasis via the modulation of E­cadherin in radically resected gastric cancer.

Gastric cancer (GC) is one of the most commonly occurring malignancies worldwide, and metastasis is one of the key processes affecting the prognosis of GC. TMEM41A, which belongs to a group of transmembrane proteins that participate in signaling pathways and tumor development, is a 264­amino acid protein encoded by a gene mapped to human chromosome The exact role of TMEM41A in GC has not been determined to date. In the present study, the expression of TMEM41A in 147 cases of GC was analyzed with immunohistohemistry and the prognoses of these patients were analyzed. It was revealed that TMEM41A was highly expressed in GC tissues, and may be associated with the progression of GC and poor prognosis. The expression of TMEM41A was observed to be correlated with lymph node metastasis, distant metastasis and advanced tumor, node and metastasis stages. Knockdown of TMEM41A in vitro and in vivo decreased the GC cell migration ability by regulating epithelial­to­mesenchymal transition and cell autophagy, via the upregulation of E­cadherin and downregulating N­cadherin expression in GC cells by reverse transcription­quantitative polymerase chain reaction (PCR), semi­PCR and western blotting. Furthermore, TMEM41A upregulation was associated with the upregulation of p62 and altered the conversion of light chain (LC)3­1 into LC3­2 by western blotting. Knockdown of TMEM41A was also observed to affect tumor metastasis in nude mice. Therefore, TMEM41A may be considered as a novel therapeutic target for the treatment of GC­associated metastasis.

[Effect of synergistic polarization macrophage modulated by N-terminal domain of a2 vacuolar ATPase and macrophage colony stimulating factor on proliferation of gastric cancer cells].

OBJECTIVE: To investigate the synergistic effect between the N-terminus domain of the a2 isoform of vacuolar ATPase (a2NTD) and macrophage colony-stimulating factor (M-CSF) on modulating macrophage polarization and the impact of polarized macrophages on proliferation of gastric cancer cells. METHODS: Peripheral blood mononuclear cells were derived from healthy donor and induced into macrophages. Then macrophages were randomly divided into four groups: the control group (RPMI 1640), the experimental group I (M-CSF 100 µg/L), the experimental group II (a2NTD 500 µg/L) and the experimental group III (a2NTD 500 µg/L plus M-CSF 100 µg/L). After stimulation for 48 hours, double color immunofluorescence cytochemistry was adopted to detect the expression of cell membrane molecules on macrophages; ELISA was used to measure the secretion of cytokines IL-10 and IL-12; CCK-8 assay was used to evaluate the impact of macrophages on proliferation ability of gastric cancer cell strain SGC-7901. RESULTS: The expression of CD68, also known as macrophage surface antigen, was detected on macrophage membrane in all four groups (+). The mean absorbance (A) was 0.092 ± 0.005 in control group, 0.095 ± 0.006 in group I, 0.094 ± 0.005 in group II, 0.094 ± 0.005 in group III, and no significant differences were observed among 4 groups (all P>0.05). Meanwhile, the expression of CD206, which mainly exists on M2 macrophage membrane, was hard to detect in control group (-) with A 0.025 ± 0.004; it was normal in groupI and group II (+) with A 0.191 ± 0.012 in group I and 0.197 ± 0.136 in group II (P=0.212), and it was up-regulated significantly in group III (+++) with A 0.285 ± 0.011. There were significant differences between either two groups except group I and group II (all P<0.01). Secretion of IL-10 in group I and group II [(85.65 ± 13.64) ng/L and (87.77 ± 14.25) ng/L] was significantly higher compared with control group [(71.67 ± 7.56) ng/L, P<0.01]. Secretion of IL-12 in group I and group II [(9.91 ± 1.50) ng/L and (10.15 ± 1.80) ng/L] was significantly lower compared with control group [(16.87 ± 1.10) ng/L, P<0.01]. Secretion of IL-10 in group III [(116.98 ± 14.27) ng/L] was the highest, and secretion of IL-12 [(5.31 ± 0.88) ng/L] was the lowest (all P<0.01). There was a synergistic effect between a2NTD and M-CSF on the secretion of both IL-10 and IL-12. Elevated proliferation of gastric cancer cell strain SGC-7901 was detected in all four groups, in which group III showed the greatest impact compared with other 3 groups (P<0.01). CONCLUSIONS: a2NTD and M-CSF show a synergistic effect in modulating macrophage phenotype and the secretion of IL-10 and IL-12. The polarized macrophage can significantly enhance proliferation of gastric cancer cell strain SGC-7901.

High expression of NEDD9 predicts adverse outcomes of colorectal cancer patients.

NEDD9, a member of Crk-associated substrate (CAS) family, is highly expressed in multiple cancer types and involved cancer cell adhesion, migration, invasion. The prognostic value of NEDD9 has not been evaluated before. The aim of this study was to evaluate the association between NEDD9 expression and survival in colorectal cancer (CRC) patients. NEDD9 expression was analyzed by immunohistochemistry in 92 patients with CRC. Patients were followed-up annually by telephone or at outpatient clinic. The results revealed that high expression of NEDD9 in 68/92 CRC samples, compared with 12/92 normal tissues (P<0.01). Correlation analysis showed high level of expression of NEDD9 was significantly correlated with advanced TNM stage (P=0.014), pT grade (P=0.009), pN (P=0.013) and pM status (P=0.047). Patients with a higher NEDD9 expression had a significantly shorter overall survival (OS) (P<0.01). The multivariate analysis revealed that NEDD9 expression could serve as an independent predictive factor of OS. Our finding demonstrated the potential value of NEDD9 expression level as a prognostic molecular marker and a target for new therapies for CRC patients.

[NF-κb inhibitor PDTC enhances tumor necrosis factor α-induced apoptosis of gastric cancer cell SGC-7901].

OBJECTIVE: To investigate the effect of PDTC (inhibitor of NF-κb) on apoptosis of human gastric cancer cell line SGC-7901 induced by tumor necrosis factor α (TNF-α) and explore the related mechanisms. METHODS: After the treatment with different concentrations of PDTC, TNF-α or PDTC combined with TNF-α on gastric cancer cell line SGC-7901, the growth inhibition of SGC-7901 was measured by MTT assay. Hoechst was used to assess SGC-7901 cell apoptosis. The protein expressions of survivin and caspase-3 were detected by Western blot assay. RESULTS: The growth inhibition rate of SGC-7901 induced by PDTC (15, 30, 60, 100 µmol/L) was (12.14±0.91)%, (20.00±1.11)%, (37.63±1.01)% and (41.46±1.07)%. Different concentrations of PDTC all inhibited the growth of SGC-7901 significantly (all P<0.01), The growth inhibition rate of SGC-7901 induced by 25 mg/L TNF-α was (2.38±0.67)%, which could not significantly inhibit the growth of SGC-7901 [control (1.50±0.81)%], while TNF-α of 50, 100, 150 mg/L could inhibit the growth of SGC-7901 significantly [(4.53±0.85)%, (4.43±0.70)% and (4.74±1.07)%, all P<0.05]. PDTC (15 µmol/L) combined with TNF-α (25, 50, 100, 150 mg/L) significantly increased the cell growth inhibition rate compared with TNF-α alone or PDTC 15 µmol/L alone (all P<0.01). Hoechst assay showed that 100 mg/L TNF-α, 15 µmol/L PDTC and combination of above two all induced cell apoptosis (P<0.01), and the combination group had significantly higher percentage of cell apoptosis (P<0.01). Survivin protein was significantly down-regulated in combination group as compared with single TNF-α (100 mg/L) group, but was not significant down-regulated as compared with single PDTC (15 µmol/L) group. Caspase-3 protein expression was significantly increased in combination group as compared with other two groups. CONCLUSION: PDTC can enhance the cell apoptosis induced by TNF-α, which may be associated with the blocking of TNF-α-activated NF-κB signaling pathway by PDTC, the down-regulation of survivin expression, and up-regulation of caspase-3 expression.

Correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2.

BACKGROUND: The relationship between the presence of metalloproteinases and thyroid cancer remains unknown, and many controversies still exist in this field. The objective of this study was to investigate the correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2. METHODS: The correlations were studied by detecting the levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 by enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the peripheral blood of 30 patients with papillary thyroid carcinoma, 27 patients with benign thyroid disease, and 25 healthy volunteers. RESULTS: The levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood of patients with papillary thyroid carcinoma were significantly higher than those in the peripheral blood of patients with benign thyroid disease and healthy volunteers (P < 0.05). However, there were no significant differences between patients with benign thyroid disease and healthy volunteers (P > 0.05). The accuracy of detection by both enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the papillary thyroid cancer group was 83.33%. CONCLUSIONS: The levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood are helpful in identifying thyroid carcinoma and aid in preoperative assessment.

Gene therapy of gastric cancer using LIGHT-secreting human umbilical cord blood-derived mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have the ability to migrate into tumors and therefore are potential vehicles for the therapy of malignant diseases. In this study, we investigated the use of umbilical cord blood mesenchymal stem cells (UCB-MSCs) as carriers for a constant source of transgenic LIGHT (TNFSF14) to target tumor cells in vivo. METHODS: Lentiviral vectors carrying LIGHT genes were constructed, producing viral particles with a titer of 2 × 10(8) TU/L. Fourteen days after UCB-MSCs transfected by LIGHT gene packaged lentivirus had been injected into mouse gastric cancer models, the expression levels of LIGHT mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Then the tumors' approximate volumes were measured. RESULTS: The treatment with MSC-LIGHT demonstrated a strong suppressive effect on tumor growth compared to treatment with MSC and NaCl (p < 0.001). Examination of pathological sections of the tumor tissues showed that the areas of tumor necrocis in the MSC-LIGHT group were larger than those in the MSC group. Moreover, we found that MSCs with LIGHT were able to significantly induce apoptosis of tumor cells. The expression levels of LIGHT mRNA and protein were significantly higher in the UCB-MSCs with the LIGHT gene than the levels in UCB-MSCs (p < 0.001). CONCLUSION: These results suggest that UCB-MSCs carrying the LIGHT gene have the potential to be used as effective delivery vehicles in the treatment of gastric cancers.

[Study of inhibiting and killing effects of transgenic LIGHT human umbilical cord blood mesenchymal stem cells on stomach cancer].

OBJECTIVE: To study the inhibition and killing effect of transgenic LIGHT umbilical cord blood mesenchymal stem cells (UCBMSCs) on stomach carcinoma. METHODS: The LIGHT gene was recombined to construct the transfer plasmid pGC-FU-LIGHT by infusion technique. The 293T cells were co-transfected with the transfer plasmid pGC-FU-LIGHT, the construction plasmid Helper 1.0 and the envelope plasmid Helper 2.0 with the help of lipofectamine 2000 to produce lentiviral particles. Transgenic UCBMSCs(MSC-LIGHT) and empty carrier UCBMSCs (MSC) were obtained. Human gastric cancer cell SGC-7901 was injected into nude mice subcutaneously groin. The model of transplanted human gastric cancer cell SGC-7901 in nude mice was established. Tumorigenesis nude mice were separated into three groups randomly with 5 in each group: MSC-LIGHT group, MSC group, and NS group. Three groups of nude mice were injected around the tumor with MSC-LIGHT, MSC and NS every other day for 3 times. Four weeks later, the transplanted gastric cancer volume was measured. The expressions of LIGHT in the three groups were determined by RT-PCR and ELISA method. The necrosis area in the tumors was calculated under pathological examination. RESULTS: The average volume of transplanted tumor was(0.45±0.25) cm(3) in MSG-LIGHT group, (0.64±0.36) cm(3) in MSG group, and(1.21±0.79) cm(3) in NS group, and the difference was statistically significant(P<0.05). The LIGHT mRNA was 2.96±0.27, 1.23±0.47, and 0.73±0.10 respectively. The LIGHT protein was(167.89±2.31), (73.22±5.74), and (49.66±5.25) ng/L. The differences were all statistically significant among the three groups(both P<0.01). Pathological examination showed that the necrosis area was largest in MSC-LIGHT group. CONCLUSION: Transgenic UCBMSCs secret LIGHT in a paracrine manner, which has inhibition and killing effects on stomach carcinoma.

[Analysis of prognostic factors for gastric stump cancer].

OBJECTIVE: To investigate the independent prognostic factors of long-term survival for gastric stump cancer after radical resection. METHODS: The clinicopathological and follow-up data of 63 patients with gastric stump cancer undergoing surgical treatment from January 1996 to December 2006 in our hospital were analyzed retrospectively, including age, gender, types of reconstruction, tumor location, histological types, TNM stages, surgical treatment, prognosis and etc. The survival was estimated using Kaplan-Meier method and compared using log-rank test. The effect of independent factors on prognosis was determined by Cox regression multivariate analysis. RESULTS: Radical resection was performed in 35 patients, including combined multiple organ resection (n=16). Surgery was palliative in 28 patients. All the 63 patients were followed up. The median survival time of these 63 patients was 21 months, and the overall 1-, 3-, 5-year survival rates were 76.2%, 31.7% and 18.8%, respectively. Univariate and multivariate analysis showed that surgical procedure, clinical stage and histological type were independent prognostic factors of gastric stump cancer, while age, gender, type of reconstruction and tumor location were not significantly correlated with prognosis. CONCLUSIONS: Radical resection, clinical stage and histological type are main prognostic factors for gastric stump cancer. Radical resection is an effective way to prolong the postoperative survival time in patients with gastric stump cancer, especially in the early stage.

TNF-α expression in the UCB-MSCs as stable source inhibits gastric cancers growth in nude mice.

Mesenchymal stem cells (MSCs) are potentially vehicles for therapy of malignant diseases. In our study, we investigated whether UCB-MSCs are capable to carry TNF-α to target tumor cells in vivo. The human gastric cancer cells SGC-7901 were subcutaneously injected into the abdomen near groins of 15 nude mice to establish experiment tumor models. MSC-TNF-α demonstrated a strong suppressive effect on the tumor growth compared with MSC and NaCl. Thus, MSC-TNF-α can obviously inhibit Gastric cancers growth in nude mice, indicating that UCB-MSCs may have the potential to become a prevention approach against gastric cancer.