Activating transcription factor 3 promotes colon cancer metastasis.

Colorectal cancer is one of the commonest of solid malignancy in the world. Activating transcription factor 3 (ATF3), a homolog of the mouse TI-241 and rat LFR-1, is a stress responsive gene that has been widely indicated in different malignancies. However, the role of ATF3 in colon cancer is paradoxical with both a suggested pro- and anti-tumorigenic role. The objective of the current study was to investigate the role of ATF3 in colon cancer metastasis using HT29 and CaCO2 colon cancer cell lines. Expression of ATF3 was initially evaluated in five pairs of colon cancer and matched noncancerous colon tissues. The role of ATF3 in promoting in vitro migration and invasion were evaluated by siRNA-mediated knockdown and adenovirus-mediated overexpression of ATF3. In addition, the role of ATF3 in promoting in vivo tumor growth and hepatic metastasis was investigated by shRNA-mediated knockdown of ATF3. Expression of ATF3 was more in the colon cancer tissues as compared with the pooled noncancerous control colon tissue. Our results showed that in both HT29 and CaCO2 cells, ATF3 promoted in vitro motility and invasion. Furthermore, knockdown of ATF3 attenuated subcutaneous tumor growth and CD31(+) neovasculature in xenograft assays with HT29 and CaCO2 cells and inhibited hepatic metastasis. Cumulatively, our results unequivocally show that ATF3 promotes colon cancer metastasis.

Combination of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging is an optimal way to evaluate rheumatoid arthritisin rats dynamically.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder. Many methods have been used to observe the progress of RA. The purpose of this study was to observe the progress of RA in rats with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), magnetic resonance (MR) imaging and arthritis score, and analyze the relationships among different methods in evaluation of RA. METHODS: Sixteen healthy Sprague Dawley (SD) rats about 8-week old were randomly assigned to a RA group and a control group. Bovine type II emulsified incomplete Freud's adjuvant was used to induce arthritis in the RA group. Arthritis score of the rats in two groups were recorded, and (18)F-FDG PET/CT, MR imaging were performed both on the corresponding rats every 3 days. All the rats were sacrificed at week 5, and histopathological examination was performed on rat knees stained with haematoxylin and eosin. RESULTS: The arthritis score and the standard uptake value (SUV) of knee joints in RA rats increased with the progression of arthritis gradually. Both peaks of arthritis score and SUV appeared at 21 days after the first immune injection, then the arthritis score and SUV of knee joints decreased slowly. The arthritis scores of knee joints in RA rats were positively correlated with their SUV changes. The MR images were confirmed by the histopathological studies. CONCLUSION: PET/CT can detect the earliest molecular metabolism changes of RA, and MR imaging can follow up the dynamical anatomical changes of RA, all of which indicated that PET/CT and MR imaging may be applied as useful tools to monitor the progress of RA.

NF-κb inhibitor PDTC enhances tumor necrosis factor α-induced apoptosis of gastric cancer cell SGC-7901 / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

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 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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%.</p><p><b>CONCLUSIONS</b>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.</p>

Quantitative T2 mapping evaluation for articular cartilage lesions in a rabbit model of anterior cruciate ligament transection osteoarthritis.

BACKGROUND: Quantitative T2 mapping has been a widely used method for the evaluation of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate ligament transection (ACLT) osteoarthritis. METHODS: Twenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II. RESULTS: The average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (P<0.001). T2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen. CONCLUSION: This study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.

Analysis of prognostic factors for gastric stump cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the independent prognostic factors of long-term survival for gastric stump cancer after radical resection.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Study of inhibiting and killing effects of transgenic LIGHT human umbilical cord blood mesenchymal stem cells on stomach cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the inhibition and killing effect of transgenic LIGHT umbilical cord blood mesenchymal stem cells (UCBMSCs) on stomach carcinoma.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Transgenic UCBMSCs secret LIGHT in a paracrine manner, which has inhibition and killing effects on stomach carcinoma.</p>

Surgical treatment and prognostic factors for obstructing left colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the outcomes of surgical treatment and the prognostic factors of long-term survival for obstructing left colorectal cancer.</p><p><b>METHODS</b>Clinicopathological and follow-up data of 93 patients with obstructing left colorectal cancer undergoing surgical treatment from January 2001 to December 2006 in the Affiliated Hospital of Medical College of Qingdao University were analyzed retrospectively.</p><p><b>RESULTS</b>There were 53 males and 40 females. The median age was 61 years old. Fifty-one patients had concurrent medical condition. Radical resection was performed in 67 patients, including one-stage resection (n=21), Hartmann procedure (n=35), and Miles procedure (n=11). Surgery was palliative in 26 patients, including diverting stoma (n=14), bypass surgery (n=7), and palliative resection (n=5). All the 93 patients were followed up. The 1-, 3-, and 5-year survival rates were 94%, 59%, and 38%, respectively. Univariate and multivariate analyses showed that radical resection, TNM staging, and preoperative level of carcinoembryonic antigen were independent prognostic factors (all P<0.05).</p><p><b>CONCLUSIONS</b>Radical resection, TNM stage, and preoperative CEA level are prognostic factors of obstructing left colorectal cancer. Early diagnosis, radical resection, and selection of appropriate surgical procedure are helpful to prolong survival time of patients with obstructing left colorectal cancer.</p>

The study of early application with Dixiong Decoction (地芎汤) for non-small cell lung cancer to decrease the incidence and severity of radiation pneumonitis: A prospective, randomized clinical trial.

OBJECTIVE: To evaluate the efficacy of compound Dixiong Decoction (地芎汤, a Chinese herbal decoction) on early prevention of radiation pneumonitis. METHODS: Forty-six patients with non-small cell lung cancer who were planning to receive radiotherapy were randomly assigned to the treatment group treated with the compound Dixiong Decoction and the control group treated with a commonly used herbal decoction which has the effects of supplementing qi and nourishing yin, clearing heat and detoxifying at the time of radiotherapy. Primary measure was the incidence of radiation pneumonitis after radiotherapy. Secondary outcomes included Watters clinical radiographic physiologic (CRP) dyspnea score, the Radiation Therapy Oncology Group (RTOG) grading score, Karnofsky Performance Status (KPS) score, and the application of corticosteroids. RESULTS: The incidence of radiation pneumonitis in the treatment group was 10.0%, while that in the control group was 26.3% (P=0.0032). The Watters CRP dyspnea score and RTOG grading score in the treatment group were significantly =lower than those in the control group (P<0.05). The KPS score in the treatment group was significantly higher than that in the control group (P<0.01). The dosage of corticosteroids was smaller with a shorter duration of therapy in the treatment group than that in the control group. CONCLUSION: The early application of the Chinese herbal decoction compound Dixiong Decoction can decrease the incidence of radiation pneumonitis, reduce the injury of the lung, and improve the life quality of the patients.

Influence of obesity on short-term surgical outcome in patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the influence of obesity on surgical procedure and short-term surgical outcome in patients with gastric carcinoma.</p><p><b>METHODS</b>A total of 426 patients with gastric carcinoma underwent laparotomy in our hospital during January 2006 and June 2008. All the patients were divided into obesity group and non-obesity group according to body mass index (BMI). The thickness of subcutaneous fat (SCF), abdominal anterior-posterior diameter (APD) and transverse diameter (TD) at the umbilicus level were measured by abdominal CT. Furthermore, the surgical data and postoperative conditions including short-term outcome were reviewed and compared between two groups.</p><p><b>RESULTS</b>The incidence of obesity was 29.8% in gastric carcinoma patients. Mean values of SCF thickness, APD and TD in obesity group and non-obesity group were (21.8+/-7.1) mm vs (14.4+/-7.5) mm, (223.2+/-24.6) mm vs (181.8+/-23.5) mm and (323.6+/-23.8) mm vs (285.8+/-24.4) mm (P=0.000). Longer operative time (P=0.007) and less amount of dissected lymph nodes were found in obesity group as compared to non-obesity group (P=0.000). Also, obesity group lasted a longer postoperative period of fever (P=0.000) and experienced more post-operative complications (P=0.005) than non-obesity group did.</p><p><b>CONCLUSIONS</b>Abdominal CT scan may display the abdominal shape of gastric carcinoma patients, hence, it is useful to evaluate the difficulty of surgical procedure. These patients may involve in complicated surgical procedure and worse short-term outcome due to obese abdominal shape. Therefore, perioperative management should be emphasized for these patients.</p>

Risk factors of intra-abdominal infection following gastrectomy in gastric cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the main risk factors associated with intra-abdominal infection(IAI) following gastrectomy in gastric cancer patients.</p><p><b>METHODS</b>Case-control study was used to investigate the clinical data of 1728 gastric carcinoma cases retrospectively by Logistic regressive analysis.</p><p><b>RESULTS</b>Univariate Logistic regressive analysis showed 16 factors, including age, malnutrition, chronic obstructive pulmonary disease(COPD), diabetes mellitus(DM), heart diseases, prothrombin time, lymphocyte count, tumor size, ascites, invasion to the adjacent organ, neoplasm TNM staging (UICC, 1997), methods of gastrectomy, blood loss, operative time, blood transfusion and extent of lymph nodal dissection,were associated with postoperative intra-abdominal infection. Binary Logistic regression analysis found that extent of lymph nodal dissection(N(2)(+) approximately N(3) and N(2)), invasion to the adjacent organ, DM, operative time, age and lymphocyte count were the independent risk factors associated with mortality.</p><p><b>CONCLUSION</b>Necessary interventions should be carried out to prevent IAI referring to above risk factors.</p>

Effect of activated greater omental milky spots and peritoneal macrophages on tumoricidal activity against gastric carcinoma SGC-7901 in mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of activated greater omental milky spots and peritoneal macrophages in mice on tumoricidal activity against gastric carcinoma SGC-7901, following intraperitoneal (i.p.) injection of INF-gamma, staphylococcin aureus or NDV-L.</p><p><b>METHODS</b>The quantitative changes of milky spots were determined by activated carbon, the number of the macrophage in milky spots was assessed by nonspecific esterase stain and the number of peritoneal macrophages was counted by trypan blue exclusion. The morphology of peritoneal macrophages was observed by scanning electron microscope, the amount of TNF-alpha and iNOS mRNA expressed by peritoneal macrophages was measured by fluorescence quantitative PCR and the cytotoxicity of peritoneal macrophages supernatant against SGC-7901 was evaluated by MTT assay.</p><p><b>RESULTS</b>It was found in the treated groups that: 1. The amount of greater omental milky spots and the macrophages in milky spots increased, 2. The number of peritoneal macrophages increased. The peritoneal macrophages were in activated status. The effect TNF-alpha and iNOS mRNA expression increased and 3. The cytotoxicity against in vitro SGC-7901 increased.</p><p><b>CONCLUSION</b>Intraperitoneal injection of IFN-gamma, staphylococcin aureus or NDV-L could activate the milky spots of the greater omentum and the macrophages in peritoneal cavity in mice, with IFN-gamma being the best. The supernatant of activated peritoneal macrophages has cytotoxicity against SGC-7901. Administration of LPS to macrophages cultured in vitro could amplify the activation and enhance the cytotoxicity of the supernatant against SGC-7901.</p>