miR-181a down-regulates MAP2K1 to enhance adriamycin sensitivity in leukemia HL-60 cells.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "miR-181a down-regulates MAP2K1 to enhance adriamycin sensitivity in leukemia HL-60 cells, by J.-J. Wang, J.-P. Yu, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2497-2504-DOI: 10.26355/eurrev_201903_17397-PMID: 30964176" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17397.

[WWP1 promotes cell proliferation in hepatocellular carcinoma through ubiquitin-degradation EI24].

Objective: To screen the interaction proteins of WW domain containing protein 1 (WWP1), and explore the effects of WWP1 and etoposide induced 24 (EI24) on cell proliferation in hepatocellular carcinoma (HCC). Methods: Yeast two-hybrid screening system was used to identify the interaction proteins of WWP1. The interaction was further validated by co-immunoprecipitation. WWP1 and EI24 stably over-expressing or deleted HepG2 cells were established by using the lentivirus transduction method. Colony forming assay and cell counting kit-8 (CCK8) assay were performed to identify the effects of WWP1 and EI24 on cell proliferation. In addition, the role of WWP1 in the tumorigenicity of liver cancer in vivo was examined by subcutaneous injection of different level of WWP1 expressed HepG2 into nude mice. Results: WWP1 can interact with EI24 and ubiquitin-degrade EI24 protein. The WWP1 and EI24 over-expressing or deleted HepG2 cell lines were successfully generated. Overexpression of WWP1 decreased while knockdown of WWP1 increased the protein level of EI24. The results of CCK-8 assay showed that the relative proliferation activities of WWP1 overexpressed (WWP1-OE) group and WWP1 knockdown (shWWP1) group on 36 hours were (347.00±8.15)% and (187.08±4.86)%, respectively, significantly different from (270.33±15.01)% of control group (both P<0.05). The relative proliferation activities of EI24 overexpressed (EI24-OE) group and EI24 knockdown (shEI24) group on 36 hours were (183.75±8.11)% and (317.33±9.60)%, respectively, significantly different from (270.33±15.01) % of control group (both P<0.05). The results of colony formation assay showed that the colony numbers of control group, WWP1-OE group and shWWP1 group were (52±7)/visual field (VF), (76±4)/VF, (19±3)/VF, respectively. Overexpression of WWP1 significantly increased while knockdown of WWP1 significantly decreased the colon formation ability of HepG2 cells (both P<0.05). The colon number of control group, EI24-OE group and shEI24 group were (38±4)/VF, (10±3)/VF, (69±7)/VF, respectively. Overexpression of EI24 significantly decreased while knockdown of EI24 significantly increased the colony formation ability of HepG2 cells (both P<0.05). The results of xenograft mice model showed that the tumor volumes of control, WWP1-OE, and shWWP1 group were (1 400.00±43.71)mm(3,) (2 636.67±290.45) mm(3) and (642.17±36.00)mm(3,) respectively, with significant differences (P<0.05). The tumor weight for these three groups were (1.23±0.08)g, (2.05±0.17)g, and (0.88±0.09)g, respectively, with significant differences (P<0.05). The tumor volumes of control, EI24-OE, and shEI24 group were (1 245.17±93.10)mm(3,) (662.17±60.88)mm(3) and (1 986.67±226.75)mm(3) respectively, with significant differences (P<0.05). The tumor weight for these three groups were (1.15±0.04)g, (0.85±0.02)g and (1.73±0.05)g respectively, with significant difference (P<0.05). Conclusion: WWP1 promote the cell proliferation of liver cancer through ubiquitin-degradation of EI24.

[The inhibition effects of apatinib on cell proliferation, migration and apoptosis in esophageal carcinoma via Ras/Raf/MEK/ERK and JAK2/STAT3 pathways].

Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 µmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 µmol/L and 40 µmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 µmol/L, 20 µmol/L and 40 µmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 µmol/L and 40 µmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G(2)/M phase and apoptosis rate of control group and 20 µmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G(2)/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 µmol/L and 40 µmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 µmol/L and 40 µmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 µmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions: Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.

miR-181a down-regulates MAP2K1 to enhance adriamycin sensitivity in leukemia HL-60 cells.

OBJECTIVE: MAPK kinase 1 (MEK1), also known as MAP2K1, plays a role in activating extra-cellular signal-regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway to regulate cell proliferation and apoptosis. The abnormal expression of MAP2K1 is associated with leukemia. Bioinformatics analysis showed the targeted relationship between microRNA-181a (miR-181a) and the 3'-UTR of MAP2K1. This study aimed to investigate the role of miR-181a in regulating MAP2K1 expression, the effects on leukemic cell proliferation, apoptosis, and adriamycin (ADM) resistance. MATERIALS AND METHODS: Dual luciferase reporter gene assay was applied to confirm the targeted relationship between miR-181a and MAP2K1. ADM resistant cell line HL-60/ADM was established. MiR-181a and MAP2K1 expressions were detected. HL-60/ADM cells were cultured in vitro and divided into two groups, including microRNA-Normal control (miR-NC) group and miR-181a mimic group. MAP2K1, phosphorylated MAP2K1 (p-MAP2K1), and phosphorylated ERK (p-ERK) protein expressions were tested. Cell apoptosis was assessed with flow cytometry. Cell proliferation was determined using EdU staining. RESULTS: There is a targeted regulatory relationship between miR-181a and MAP2K1 mRNA. miR-181a expression was significantly lower, while MAP2K1 mRNA and protein expressions were markedly higher in HL-60/ADM cells than HL-60 cells (p<0.05). Transfection of miR-181a mimic markedly reduced expressions of MAP2K1, p-MAP2K1, and p-ERK in HL-60/ADM cells, enhanced cell apoptosis, and weakened cell proliferation compared to miR-NC (p<0.05). CONCLUSIONS: MiR-181a reduction and MAP2K1 elevation were related to ADM resistance in leukemia cells. Up-regulation of miR-181a expression inhibited leukemia cell proliferation, induced apoptosis, and reduced ADM resistance via targeting MAP2K1 expression and ERK/MAPK signaling pathway.

Contrast-Enhanced 3D-FLAIR Imaging of the Optic Nerve and Optic Nerve Head: Novel Neuroimaging Findings of Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: The sensitivity of contrast-enhanced 3D-FLAIR has not been assessed in patients with idiopathic intracranial hypertension. The purpose of this study was to evaluate whether hyperintensity of the optic nerve/optic nerve head on contrast-enhanced 3D-FLAIR imaging is associated with papilledema in patients with idiopathic intracranial hypertension. MATERIALS AND METHODS: A retrospective review was conducted from 2012 to 2015 of patients with clinically diagnosed idiopathic intracranial hypertension and age- and sex-matched controls who had MR imaging with contrast-enhanced 3D-FLAIR. Two neuroradiologists graded each optic nerve/optic nerve head on a scale of 0-3. This grade was then correlated with the Frisén Scale, an ophthalmologic scale used for grading papilledema from 0 (normal) to 5 (severe edema). To estimate the correlation between the MR imaging and Frisén scores, we calculated the Kendall τ coefficient. RESULTS: Forty-six patients (3 men, 43 women) with idiopathic intracranial hypertension and 61 controls (5 men, 56 women) with normal findings on MR imaging were included in this study. For both eyes, there was moderate correlation between the 2 scales (right eye: τ = 0.47; 95% CI, 0.31-0.57; left eye: τ = 0.38; 95% CI, 0.24-0.49). Interreader reliability for MR imaging scores showed high interreader reliability (right eye: κ = 0.76; 95% CI, 0.55-0.88; left eye: κ = 0.87; 95% CI, 0.78-0.94). Contrast-enhanced 3D-FLAIR imaging correlates with the Frisén Scale for moderate-to-severe papilledema and less so for mild papilledema. CONCLUSIONS: Hyperintensity of the optic nerve/optic nerve head on contrast-enhanced 3D-FLAIR is sensitive for the detection of papilledema in patients with idiopathic intracranial hypertension, which may be useful when prompt diagnosis is crucial.

Midline preperitoneal repair for incarcerated and strangulated femoral hernia.

OBJECTIVE: Femoral hernias constantly present as incarceration or strangulation and require emergency surgery. Incarcerated and strangulated femoral hernia repair remains challenging and controversial. The aim of our study was to analyze the efficacy of preperitoneal tension-free hernioplasty via lower abdominal midline incision for incarcerated and strangulated femoral hernia. METHODS: Data of 47 patients who underwent emergency surgery for incarcerated or strangulated femoral hernias from January 2009 to December 2017 were retrospectively analyzed. According to the surgical incisions, they were divided into two groups: the observation group (21 cases) had a lower abdominal midline incision, and the control group (26 cases) had a traditional inguinal incision. General data of patients, intraoperative findings, operative time and postoperative complications were compared. RESULTS: Patient characteristics showed that the two groups were comparable.15 cases (31.9%) underwent intestinal resection, and 32 cases (68.1%) underwent first-stage tension-free repair in total. The rate of first-stage tension-free hernioplasty was significantly higher in the observation group (18/21, 85.7% vs 14/26 53.8%, P = 0.020). No additional incision was required in the observation group, while six cases of the control group (23.1%) had an additional incision for intestinal resection and anastomosis (P = 0.026). Mean operative time (53.6 ± 24.7 min vs 77.9 ± 36.5 min, P = 0.012) and the length of hospital stay (6.3 ± 4.2 days vs 10.3 ± 6.9 days, P = 0.020) were significantly shorter in the observation group. The time of return to normal physical activity resulted significantly reduced compared to the control group (9.2 ± 4.1 days vs 13.3 ± 6.6 days, P = 0.017). The total incidence of postoperative complication (including chronic pain, foreign body sensation, hernia recurrence, wound infection and seroma/hematomas) in the observation group was lower (14.3% vs 42.3% P = 0.037). There were two recurrences in the control group. No mesh-related infection and no mortalities in two groups. CONCLUSIONS: Midline preperitoneal approach for incarcerated and strangulated femoral hernia is a convenient and effective technique. It can improve the rate of first-stage tension-free repair of incarcerated femoral hernia and allow intestinal resection through the same incision, and with lower rate of postoperative complications.

[Effect of image fusion technology of radioactive particles implantation before and after the planning target and dosimetry].

Objective: To compare the post-implant target volumes and dosimetric evaluation with pre-plan, the gross tumor volume(GTV) by CT image fusion-based and the manual delineation of target volume in CT guided radioactive seeds implantation. Methods: A total of 10 patients treated under CT-guidance (125)I seed implantation during March 2016 to April 2016 were analyzed in Peking University Third Hospital.All patients underwent pre-operative CT simulation, pre-operative planning, implantation seeds, CT scanning after seed implantation and dosimetric evaluation of GTV.In every patient, post-implant target volumes were delineated by both two methods, and were divided into two groups. Group 1: image fusion pre-implantation simulation and post-operative CT image, then the contours of GTV were automatically performed by brachytherapy treatment planning system; Group 2: the contouring of the GTV on post-operative CT image were performed manually by three senior radiation oncologists independently. The average of three data was sets. Statistical analyses were performed using SPSS software, version 3.2.0. The paired t-test was used to compare the target volumes and D(90) parameters in two modality. Results: In Group 1, average volume of GTV in post-operation group was 12-167(73±56) cm(3). D(90) was 101-153 (142±19)Gy. In Group 2, they were 14-186(80±58)cm(3) and 96-146(122±16) Gy respectively. In both target volumes and D(90), there was no statistical difference between pre-operation and post-operation in Group 1.The D(90) was slightly lower than that of pre-plan group, but there was no statistical difference (P=0.142); in Group 2, between pre-operation and post-operation group, there was a significant statistical difference in the GTV (P=0.002). The difference of D(90) was similarly (P<0.01). Conclusion: The method of delineation of post-implant GTV through fusion pre-implantation simulation and post-operative CT scan images, the contours of GTV are automatically performed by brachytherapy treatment planning system appears to have improved more accuracy, reproducibility and convenience than manual delineation of target volume by maximum reduce the interference from artificial factor and metal artifacts. Further work and more cases are required in the future.

[Next generation sequencing technology for susceptible gene screening in familial non-medullary thyroid carcinoma].

Objective: To screen genes related to familial non-medullary thyroid carcinoma (FNMTC) using next-generation sequencing (NGS). Methods: A panel of NGS was designed and sequencing was performed for DNA samples extracted from peripheral blood leukocytes of FNMTC patients and sporadic non-medullary thyroid carcinoma (SNMTC) cases, respectively, and gene mutations were screened. In addition, the clinicopathological characteristics, including tumor size, extension of surgery, lymph node metastasis and extra-thyroidal extension, were compared between patients with or without mutations. Results: In 63 NMTC samples, 45 mutations were detected on 13 genes. 37 germline mutations were detected in 47 FNMTC patients, while 8 germline mutations were detected in 16 SNMTC patients. In 8 FNMTC family lineages, the same mutations were carried by FNMTC patients from the same pedigree. The number of carriers of mutations was 29 in the 47 FNMTC patients and 6 in the 16 SNMTC patients, with a non-significant difference (P= 0.092). Among the FNMTC patients, there were 22 patients with central lymph node metastasis in the 29 mutation-positive patients, significantly more than 7 in the 16 mutation-negative cases (P= 0.031). As for the parentage, there were 3 patients with central lymph node involvement among the 7 patients of parent generation, while all the 9 patients of offspring generation had central lymph node metastasis (P=0.019). Conclusions: This panel of NGS can be used to screen mutant susceptibility gene of FNMTC patients, and the findings may be helpful for early detection of FNMTC patients and predicting the disease risk to familial members of FNMTC patients.

[Pathologic response and changes of serum VEGF during chemoradiotherapy may predict prognosis in non-surgical patients with esophageal carcinoma].

OBJECTIVE: To observe the pathological response in the tumor tissue and the changes of serum level of vascular endothelial growth factor (VEGF) in esophageal cancer patients receiving concurrent chemoradiotherapy, in order to study the impacts of these two factors on the prognosis of patients. METHODS: One hundred pathologically confirmed esophageal cancer patients were treated with radiotherapy including 72 patients with concurrent chemoradiotherapy. After 4 weeks, gastroscopy was performed to collect tumor biopsies for examination of pathological changes. The responses to radiotherapy were classified into three degrees: mild, moderate and intensive. Moreover, serum samples were collected from the patients prior to, at the fourth week during radiotherapy, and one week after radiotherapy, and serum VEGF level was determined. The changes of serum VEGF were classified as increased, unchanged and decreased. Serum samples from 30 healthy subjects were collected and represented as VEGF healthy control. RESULTS: Among the eighty-nine patients evaluable, the 1- and 3-year overall survival (OS) rates were 70.8% and 33.3%, respectively; 1-year and 3-year progression-free survival (PFS) rates were 61.8% and 28.2%, respectively; and 1-year and 3-year local control (LC) rates were 76.9% and 50.0%, respectively. The 1-year OS rates in the patients with mild, moderate and intensive pathological responses were 50.0%, 76.9% and 78.0%, respectively. The 1-year OS rate in the mild response group was significantly lower than that in the intensive response group (P<0.05). The 1-year and 3-year PFS rates in the three groups were 36.4%, 73.1%, 68.3%, and 0.0%, 40.0% and 38.9%, respectively, showing that the rate in the mild response group was significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The PFS rate in the mild response group was significantly lower than that in the moderate and intensive response groups(P<0.05 for both). Moreover, the 1-year local control (LC) rates in the three groups were 52.9%, 83.3% and 83.8%, and the three-year LC rates were 0.0%, 64.3% and 64.0%, respectively, showing that the lowest LC rates in the mild response group were significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The average serum VEGF levels in the patients prior to, during and after radiotherapy were (109.6±33.7) ng/L, (101.2±24.3) ng/L and (99.5±22.9) ng/L, respectively, all significantly higher than that in the healthy subjects [(79.6±39.2) ng/L, P<0.05 for both]. The level of serum VEGF was decreased during and after radiotherapy compared with that before radiotherapy (F=6.124, P=0.004). The 1-year OS rates in the VEGF-increased, unchanged and decreased groups were 50.0%, 67.4% and 86.7%, respectively, and the 3-year OS rates in these three groups were 15.4%, 27.0% and 50.0%, respectively. The OS rates in the increased group were significantly lower than that in the VEGF-decreased group (P<0.05). Moreover, the 3-year PFS rates in the three groups were 7.7%, 21.6% and 46.4%, respectively, and the rate in the VEGF-increased group was significantly lower than that in the VEGF-decreased group (P<0.05). The multi-variate analysis showed that TNM stage, pathological response and serum VEGF were independent factors affecting the survival in the non-surgical patients with esophageal cancer (P<0.05 for all). CONCLUSIONS: Tumor tissue pathological response and variation of serum VEGF level in response to chemoradiotherapy can be used to predict the efficacy of chemoradiotherapy in non-surgical patients with esophageal cancer. Hence, monitoring the pathological response and VEGF changes during the course of therapy is of utmost importance to evaluate and perform an individualized therapy in clinical practice.

The AKT1/NF-kappaB/Notch1/PTEN axis has an important role in chemoresistance of gastric cancer cells.

The inherent resistance of tumors to DNA damage often limits the efficacy of chemotherapy. The aim of this work is to explore the potential mechanism for development of chemoresistance in gastric cancer. Our data revealed that AKT1 mRNA and protein expression were induced by doxorubicin (a chemotherapeutic agent); the doxorubicin-induced AKT1 expression and activation increased the binding of NF-kappaB on Notch1 DNA promoter and then promoted the Notch1 transcription and expression; enhanced expression of Notch1 further upregulated PTEN expression through CBF-1 binding to PTEN DNA promoter; and inhibition of AKT1 expression and activity sensitized the gastric cancer cell to doxorubicin treatment in cultured gastric cancer cell lines and xenograft nude mice gastric cancer model. Furthermore, our data demonstrated that both Notch1 and PTEN were absent or minimally expressed in gastric cancer tissue but abundant in paired normal gastric mucosa, and the expression of Notch1 correlated with that of PTEN. Together, these novel results suggested that a novel AKT1/NF-kappaB/Notch1/PTEN axis has an important role in the development of chemoresistance in gastric cancer. Notch1 has an anti-cancer role in gastric cancer.

Super-resolution track density imaging of glioblastoma: histopathologic correlation.

BACKGROUND AND PURPOSE: Super-resolution track density imaging generates anatomic images with submillimeter voxel resolution by using high-angular-resolution diffusion imaging and fiber-tractography. TDI within the diseased human brain has not been previously described. The purpose of this study was to correlate TDI with histopathologic features of GBM. MATERIALS AND METHODS: A total of 43 tumor specimens (24 contrast-enhancing, 12 NE, and 7 centrally necrotic regions) were collected from 18 patients with treatment-naïve GBM by use of MR imaging-guided neurosurgical techniques. Immunohistochemical stains were used to evaluate the following histopathologic features: hypoxia, architectural disruption, microvascular hyperplasia, and cellular proliferation. We reconstructed track density maps at a 0.25-mm isotropic spatial resolution by using probabilistic streamline tractography combined with constrained spheric deconvolution (model order, 8; 0.1-mm step size; 1 million seed points). Track density values were obtained from each tissue site. A P value of .05 was considered significant and was adjusted for multiple comparisons by use of the false discovery rate method. RESULTS: Track density was not significantly different between contrast-enhancing and NE regions but was more likely to be elevated within regions demonstrating aggressive histopathologic features (P < .05). Significant correlation between relative track density and hypoxia (odds ratio, 3.52; P = .01), architectural disruption (odds ratio, 3.49; P = .03), and cellular proliferation (odds ratio, 1.70; P = .05) was observed irrespective of the presence or absence of contrast enhancement. CONCLUSIONS: Numeric values of track density correlate with GBM biologic features and may be clinically useful for identification of regions of tumor infiltration within both enhancing and NE components of GBM.

A safe and efficient strategy for endoscopic resection of large, gastrointestinal lipoma.

BACKGROUND: Gastrointestinal (GI) lipomas are benign, slowly growing, submucosal tumors, which may cause gastrointestinal bleeding, anemia, intussusception, and bowel obstruction. The aim of this study is to explore the safe and effective strategy for endoscopic removal of large GI lipomas. METHODS: During last 10 years, fifteen large and symptomatic GI lipomas were resected under endoscopy in our hospital. In them, two large lipomas with small stalk (< 2 m in diameter) were resected by polypectomy; ten large lipomas with base size greater than 2 cm in diameter were removed using a "subtotal resection." Three other large lipomas with small stalk (< 2 m in diameter) were resected by multistep resection. Endoscopic ultrasonography (EUS) and miniprobe endoscopic ultrasound were performed in six cases from January 2000 to July 2004 to confirm that those lesions were lipomas that were superficial to the muscularis propria. RESULTS: All 15 lesions were successfully removed and were histopathologically confirmed to be lipomas. No severe complications, such as perforation or hemorrhage, developed after endoscopic removal. No recurrence was observed after 1-8 years follow-up endoscopic examination. CONCLUSIONS: Various, large GI lipomas can be removed safely by electrosurgical snare resection under endoscopy following the guidance of the present therapeutic strategy.

Evaluation and analysis of colonoscopy in the diagnosis of 186 cases of ulcerative colitis patients.

The objective of this study was to evaluate the diagnostic value of colonoscopy plus biopsy in patients with ulcerative colitis (UC). Retrospective analysis was performed on clinical data in 186 cases. Erosions, or ulcers, together with mucosal hyperemia and oedema were the most common manifestations of colonoscopy in 87% of patients. In about 56.4% of 186 cases, such manifestations occurred in the rectum and the sigmoid colon. Nearly 65.6% of the patients had a chronic intermittent clinical course. One case developed colon cancer, and another case had toxic megacolon; each case represents 0.05% of the total 186 patients. Therefore, prevalence of both malignancy and complication is low. Colonoscopy plus biopsy is considered to be the major means of the diagnosis of UC, demonstrating its value in differential diagnosis.

Activation of Akt and ERK signalling pathways induced by etoposide confer chemoresistance in gastric cancer cells.

AIMS: To identify whether phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinases signalling pathways are implicated in the chemoresistance of gastric cancer and to explore the possible mechanisms. METHODS: Gastric cancer cell lines SGC7901 and BGC823 were exposed to etoposide, Wortmannin+etoposide or PD98059+etoposide. Cell cycle distribution and cell apoptosis were detected using flow cytometry and Hoechst 33258 staining. Cells viability was determined by a colourimetric assay utilising 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Akt activity was detected using non-radioactive immunoprecipitation-kinase assay. Western blotting was exploited to evaluate the level of phosphorylated ERK1/2 and expressions of c-Myc and p53 protein. RESULTS: Etoposide suppressed the viability of SGC7901 and BGC823 cells in a time- and dose-dependent manner; PD98059 and Wortmannin were able to enhance the cytotoxicity of etoposide. The apoptotic levels of cells treated with Wortmannin+etoposide or PD98059+etoposide were significantly higher than those of cells treated with etoposide only. Phospho-ERK1/2, Akt activity and expression of c-Myc were significantly induced by etoposide in a time-dependent manner; moreover, there was a weak effect on the expression of p53 protein. Both Wortmannin and PD98059 elevated the level of p53 expression strikingly, however, only PD98059 suppressed the up-regulation trend of c-Myc expression induced by etoposide. CONCLUSION: Chemotherapy reagent activated phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase/extracellular-regulated protein kinases signalling pathways, which decreased the chemotherapy sensitivity of gastric cancer cell lines SGC7901 and BGC823 via suppressing the expression of p53 and enhancing the expression of c-Myc. This may be one of the molecular mechanisms of gastric cancer chemoresistance.

Clinical investigation on coexisting of duodenal ulcer and gastric cancer in China.

The aim of this study was to investigate the prevalence of coexistent duodenal ulcer and gastric cancer in China, then to explore the features of clinical manifestations, endoscopy, pathology and possible pathogenesis. A retrospective analysis has been made on medical records in Remin Hospital, Wuhan University, Hubei Province, China from January 1991 to December 2002. 37 cases of coexistent duodenal ulcer and gastric cancer were found. 24.3% (9/37) had previous history of duodenal ulcer. 81.0% (30/37) of them lack alarm symptoms or signs and 87.1% (27/31) had alleviation in abdominal pain by acid inhibitor. Duodenal ulcer was single in all cases with seven in A1 stage, three in A2 stage, one in H1 stage, one in H2 stage, seven in S1 stage and 18 in S2 stage. 89.2% (33/37) of concurrent gastric cancer were in the corpus and antrum, with 78.1% (29/37) of them belonging to Bormann type II and 87.1% (27/37) being moderately differentiated adenocarcinoma. 83.7% of patients (31/37) had positive rapid urease test. The coexisting gastric cancer in patients with duodenal ulcer is infrequent but not rare. Gastroscopy screening and routine follow-up are necessary for patients with duodenal ulcer. Helicobacter pylori may be important pathogen for it. Helicobacter pylori eradication is recommended in patients with duodenal ulcer to reduce the risk of contaminant gastric cancer.

The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells.

BACKGROUND: Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. MATERIALS AND METHODS: After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. RESULTS: ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. CONCLUSION: Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells.

[Effects of 18 alpha-glycyrrhizic acid on rat liver cytochrome P450 isoenzymes and phase II transferase].

AIM: To study the effect of 18 alpha-glycyrrhizic acid (18 alpha-GL) on hepatic microsomal drug metabolizing enzymes in rats. METHODS: 18 alpha-GL (12.5, 50.0 mg.kg-1.d-1) were given i.p. to male Wistar rats for 3, 6 or 12 consecutive days. The rats were sacrificed 24 h after the last dose and the liver microsomes were prepared for analysis of cytochrome P450 (CYP) isozymes and phase II transferase activites. RESULTS: Aniline hydroxylase (CYP2E1) activities in the rats treated with 18 alpha-GL (12.5, 50.0 mg.kg-1) for 6 days decreased dose-dependently by up to 53.2%; For 3, 6 or 12 days 7-ethoxyresorufin O-deethylase (CYP1A1) activities in the rats of 50 mg.kg-1 dose group decreased time-dependently by 17.6%, 38.3% and 47.3%, respectively; Erythromycin N-demethylase (CYP3A) activities was significantly inhibited from 23.1% to 34.3%. UDP-glucuronosyltransferase activities toward 7-hydroxy-4-methylcoumarin significantly increased ranging from 19.3% to 29.9%. UDP-glucuronosyltransferase activities toward 4-phenylphenol in the rats treated with 18 alpha-GL (12.5, 50.0 mg.kg-1) for 6 days increased by 45.9% and 70.3%. Glutathione S-transferase (GST) activities in the rats treated with 18 alpha-GL (12.5, 50.0 mg.kg-1) for 6 days increased by 13.7% and 48.3% in dose-dependent manner. CONCLUSION: 18 alpha-GL inhibited rat liver microsomal cytochrome P450 while induced phase II transferase.

Long-term potentiation induced by nicotine in CA1 region of hippocampal slice is Ca(2+)-dependent.

AIM: To observe the effects of Ca2+ on hippocampal long-term potentiation (LTP) induced by nicotine in CA1 region of rat hippocampal slice. METHODS: Extracellularly recorded population spikes (PS) of the pyramidal cell layer in the hippocampal CA1 region in vitro. RESULTS: Nicotine 1 mumol.L-1 induced LTP in the hippocampal CA1 region. It did not induce LTP in CA1 region when CA2+ was removed from artificial cerebrospinal fluid (ACSF). Nifedipine 1 and 10 mumol.L-1 partly inhibited LTP induced by nicotine, and thapsigargin 1 and 10 mumol.L-1 completely inhibited LTP induced by nicotine. CONCLUSION: LTP induced by nicotine in hippocampal CA1 region is Ca(2+)-dependent. Both Ca2+ influx and Ca2+ release participate in the induction of LTP.

Pathway of glycogen metabolism in Methanococcus maripaludis.

Methanococcus maripaludis, a facultatively autotrophic archaebacterium that grows with H2 or formate as the electron donor, does not assimilate sugars and other complex organic substrates. However, glycogen is biosynthesized intracellularly and commonly reaches values of 0.34% of the cellular dry weight in the early stationary phase. To determine the pathway of glycogen catabolism, specific enzymes of sugar metabolism were assayed in cell extracts. The following enzymes were found (specific activity in milliunits per milligram of protein): glycogen phosphorylase, 4.4; phosphoglucomutase, 10; glucose-6-phosphate isomerase, 9; 6-phosphofructokinase, 5.6, fructose-1,6-bisphosphatase, 10; fructose-1,6-bisphosphate aldolase, 4.2; triosephosphate isomerase, 44; glyceraldehyde-3-phosphate dehydrogenase, 26; phosphoglycerate kinase, 20; phosphoglycerate mutase, 78; enolase, 107; and pyruvate kinase, 4.0. Glyceraldehyde-3-phosphate dehydrogenase was NADP+ dependent, and the pyruvate kinase required MnCl2. The 6-phosphofructokinase had an unusually low pH optimum of 6.0. Four nonoxidative pentose-biosynthetic enzymes were found (specific activity in milliunits per milligram of protein): transketolase, 12; transaldolase, 24; ribulose-5-phosphate-3-epimerase, 55; and ribulose-5-phosphate isomerase, 100. However, the key enzymes of the oxidative pentose phosphate pathway, the reductive pentose phosphate pathway, and the classical and modified Entner-Duodoroff pathways were not detected. Thus, glycogen appears to be catabolized by the Embden-Meyerhoff-Parnas pathway. This result is in striking contrast to the nonmethanogenic archaebacteria that have been examined, among which the Entner-Doudoroff pathway is common. A dithiothreitol-specific NADP(+)-reducing activity was also found (8.5 mU/mg of protein). Other thiol compounds, such as cysteine hydrochloride, reduced glutathione, and 2-mercaptoethanesulfonic acid, did not replace dithiothreitol for this activity. The physiological significance of this activity is not known.

Endoscopic treatment of submucosal lesions of the gastrointestinal tract.

Fourteen of symptomatic submucosal lesions located in the esophagus (n = 4), stomach (n = 4), duodenum (n = 1) and colon (n = 5) were treated by means of endoscopy. Treatment selection criteria for tumours (n = 10) were presence of a pedunculated tumour, or presence of a sessile tumour with a base smaller than 2 cm which originated in the upper wall layers, as judged by the mobility of the lesion. All tumours but one were successfully and completely removed by snare cauterization. The failure was a gastric fibroma which was incompletely resected; bleeding ensued rendering emergency surgery necessary. Mucosal cysts in the esophagus and colon were treated by either snare polypectomy in the case of smaller lesions or drainage in the case of larger cysts. Follow-up for 5 to 12 months (mean 8.7 months) in the 13 cases treated by means of endoscopy alone did not reveal recurrence. These preliminary results show that endoscopic treatment of smaller and superficially originating submucosal tumours may be a feasible alternative to surgery, however meticulous patient selection is necessary to avoid major complications.