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1.
Chinese Journal of Gastrointestinal Surgery ; (12): 403-412, 2021.
Article in Chinese | WPRIM | ID: wpr-942902

ABSTRACT

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.


Subject(s)
Female , Humans , Male , Chemotherapy, Adjuvant , Gastrectomy , Neoadjuvant Therapy , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/surgery
2.
Chinese Journal of Gastrointestinal Surgery ; (12): 101-106, 2021.
Article in Chinese | WPRIM | ID: wpr-942871

ABSTRACT

Local advanced gastric cancer (LAGC) accounts for a large proportion of annual newly diagnosed gastric cancer patients in China. There is a general consensus for D2 radical gastrectomy followed by postoperative adjuvant chemotherapy for LAGC patients, and this therapeutic strategy has been confirmed by a series of clinical trials to obviously improve the patients' prognosis; however, the recurrence rate is still high (about 50%-80% in advanced stage), which makes it difficult to further improve the long-term survival. Perioperative therapy, especially whether preoperative neoadjuvant therapy (NAT) can improve the efficacy of patients with LAGC, has been paid more and more attention. NAT is mainly defined as a preoperative chemotherapy or chemoradiotherapy, aiming at increasing curative resection rate by downstaging tumor, eliminating micrometastases, and autologously testing of anti-cancer drug sensitivity etc. However, there are still some controversy whether LAGC patients could gain survival benefit from NAT and also lack of general consensus for this issue. In this paper, the author reviews and analyzes the current situation of perioperative therapies for LAGC patients, especially emphasize the results of neoadjuvant chemotherapy or chemoradiotherapy reported by various high-level clinical studies. The preliminary effect of perioperative chemotherapy combined with molecular targeted or immunotherapy has also aroused great interest and attention. While we continue to carry out NAT and look forward to more new high-level evidence trials on NAT, we must emphasize again that R0 gastrectomy remains the most important therapeutic modality for the patients with LAGC.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Gastrectomy/methods , Lymph Node Excision , Neoadjuvant Therapy , Neoplasm Staging , Perioperative Care/trends , Stomach Neoplasms/therapy
3.
Neuroscience Bulletin ; (6): 1091-1099, 2018.
Article in English | WPRIM | ID: wpr-775455

ABSTRACT

Although extensively studied, the exact role of sleep in learning and memory is still not very clear. Sleep deprivation has been most frequently used to explore the effects of sleep on learning and memory, but the results from such studies are inevitably complicated by concurrent stress and distress. Furthermore, it is not clear whether there is a strict time-window between sleep and memory consolidation. In the present study we were able to induce time-locked slow-wave sleep (SWS) in mice by optogenetically stimulating GABAergic neurons in the parafacial zone (PZ), providing a direct approach to analyze the influences of SWS on learning and memory with precise time-windows. We found that SWS induced by light for 30 min immediately or 15 min after the training phase of the object-in-place task significantly prolonged the memory from 30 min to 6 h. However, induction of SWS 30 min after the training phase did not improve memory, suggesting a critical time-window between the induction of a brief episode of SWS and learning for memory consolidation. Application of a gentle touch to the mice during light stimulation to prevent SWS induction also failed to improve memory, indicating the specific role of SWS, but not the activation of PZ GABAergic neurons itself, in memory consolidation. Similar influences of light-induced SWS on memory consolidation also occurred for Y-maze spatial memory and contextual fear memory, but not for cued fear memory. SWS induction immediately before the test phase had no effect on memory performance, indicating that SWS does not affect memory retrieval. Thus, by induction of a brief-episode SWS we have revealed a critical time window for the consolidation of hippocampus-dependent memory.


Subject(s)
Animals , Mice , Cues , Electroencephalography , Electromyography , Evoked Potentials, Motor , Physiology , Fear , Psychology , Glutamate Decarboxylase , Metabolism , Hippocampus , Physiology , Light , Luminescent Proteins , Genetics , Metabolism , Maze Learning , Physiology , Memory Consolidation , Physiology , Mice, Inbred C57BL , Mice, Transgenic , Sleep Deprivation , Sleep, Slow-Wave , Physiology , Time Factors , Vesicular Inhibitory Amino Acid Transport Proteins , Genetics , Metabolism
4.
Chinese Journal of Gastrointestinal Surgery ; (12): 101-103, 2013.
Article in Chinese | WPRIM | ID: wpr-314850

ABSTRACT

The incidence of gastric cancer has declined worldwide in the past decades. However, due to the large number of population in mainland of China, the absolute number of newly-diagnosed patients in this developing country is still very high. Most of the major clinical centers have established multi-disciplinary team, but the strategy in treating this life-threatening disease still needs to be optimized, including the precise preoperative staging by various techniques, perioperative chemotherapy for locally advanced diseases, role of minimally invasive surgical approaches in treating patients with different stages, translational research to fill the gap between clinical trials and basic research, as well as the individualized treatment for gastric cancer. We believe that the biological behaviors and molecular events of gastric cancer in eastern countries are different from that of Western countries, so the clinical evidences derived from Eastern countries need to be strengthened to enrich the unmet demands in the clinical practice in China.


Subject(s)
Humans , China , Combined Modality Therapy , Stomach Neoplasms , Drug Therapy , General Surgery , Therapeutics
5.
Chinese Journal of Gastrointestinal Surgery ; (12): 114-117, 2013.
Article in Chinese | WPRIM | ID: wpr-314846

ABSTRACT

A more differentiated therapy regimen for gastric carcinoma requires more precise preoperative staging. In patients with early gastric cancer (EGC), especially mucosa, endoscopic resection (ER) should be performed to avoid unnecessary surgical procedures. To achieve R0 resection for locally-advanced gastric cancer (AGC), neoadjuvant treatments have been investigated. Clinical staging of gastric cancer has been greatly improved by advance in imaging techniques such as endoscopic ultrasonography (EUS), transabdominal ultrasonography (TAUS), multi-slice spiral CT (MSCT), magnetic resonance imaging (MRI), positron emission tomography (PET), combined PET-CT scans, and laparoscopic staging. This review is to summarize the clinical application and the value of preoperative staging in gastric cancer.


Subject(s)
Humans , Diagnostic Imaging , Methods , Neoplasm Staging , Preoperative Care , Stomach Neoplasms , Diagnosis , General Surgery
6.
Chinese Medical Journal ; (24): 1826-1831, 2013.
Article in English | WPRIM | ID: wpr-273087

ABSTRACT

<p><b>BACKGROUND</b>Multidrug-resistant Acinetobacter baumannii (MDRAB) is an important and emerging hospital-acquired pathogen worldwide. This study was conducted to identify the sources of MDRAB and its role in respiratory tract colonization and nosocomial pneumonia in intensive care unit (ICU) patients.</p><p><b>METHODS</b>We conducted a prospective active surveillance study of MDRAB in three ICUs at a Chinese Hospital from April to August 2011, to identify the sources of MDRAB and its role in respiratory tract colonization and nosocomial pneumonia.</p><p><b>RESULTS</b>One hundred and fourteen (13.0%) MDRAB isolates were detected from 876 specimens, with a sensitivity of 11.6% (55/474) in screening of the pharyngeal and tracheal swabs, and 14.7% (59/402) of the sputum/endotracheal aspirates. MDRAB colonization/infection was found in 34 (26.8%) of 127 patients, including 16 (12.6%) cases of pure colonization and 18 (14.2%) cases of pneumonia (two pre-ICU-acquired cases of pneumonia and 16 ICU-acquired cases of pneumonia). Previous respiratory tract MDRAB colonization was found in 22 (17.3%) patients: eight (6.3%) were pre-ICU-acquired colonization and 14 (11.0%) ICU-acquired colonization. Of eight pre-ICU-colonized patients, five were transferred from other wards or hospitals with hospitalization > 72 hours, and three came from the community with no previous hospitalization. Overall, 6/22 colonized patients presented with secondary pneumonia; only two (9.1%) colonized MDRAB strains were associated with secondary infections. Respiratory tract MDRAB colonization had no significant relationship with nosocomial pneumonia (P = 0.725). In addition, acute respiratory failure, mechanical ventilation, renal failure, and prior carbapenem use were risk factors for MDRAB colonization/infection.</p><p><b>CONCLUSIONS</b>A high proportion of cases of MDRAB colonization/infection in ICU patients were detected through screening cultures. About one-third were acquired from general wards and the community before ICU admission. The low incidence of MDRAB colonization-related pneumonia questions the appropriateness of targeted antibiotic therapy.</p>


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Acinetobacter baumannii , Virulence , Anti-Bacterial Agents , Therapeutic Uses , Cross Infection , Drug Therapy , Microbiology , Drug Resistance, Multiple, Bacterial , Intensive Care Units , Pneumonia , Drug Therapy , Microbiology , Prospective Studies , Respiratory Tract Infections , Drug Therapy , Microbiology
7.
Chinese Journal of Oncology ; (12): 592-595, 2012.
Article in Chinese | WPRIM | ID: wpr-307336

ABSTRACT

<p><b>OBJECTIVE</b>To determine the expression patterns of metastasis associated 1 family member 2 (MTA2) in gastric cancer and non-cancerous gastric mucosa, and analyze its relationship with nuclear transcription factor Sp1 expression.</p><p><b>METHODS</b>Tissue samples and clinicopathological information from 83 gastric cancer patients, who underwent surgery, were collected from Shanghai Rui Jin Hospital. All samples included cancer tissue and non-cancerous mucosa which was 5 cm away from the tumor lesion. The expression of MTA2 and Sp1 were detected by immunohistochemistry (IHC) staining. The mRNA of MTA2 was also detected by reverse transcription-polymerase chain reaction (RT-PCR). SPSS software was used for statistical analysis.</p><p><b>RESULTS</b>The expression of MTA2 protein was significantly higher in primary lesions of the gastric cancer than that in non-cancerous mucosa by IHC (31.3% vs 12.0%, P < 0.01). MTA2 expression was closely related with tumor invasion or T staging (χ(2) = 5.677, P < 0.05). Yet, no significant relationship was observed between MTA2 expression and other clinicopathological parameters, including the age, sex, tumor differentiation, Lauren classification, lymph node metastasis, distant metastasis, as well as pathological staging. Furthermore, MTA2 expression was concomitant with Sp1 expression (r = 0.320, P < 0.05). Elevated MTA2 expression was observed in Sp1 positive cancer tissues (χ(2) = 9.565, P < 0.01). RT-PCR results also demonstrated that MTA2 mRNA was also highly expressed in the tissue samples with Sp1 expression.</p><p><b>CONCLUSIONS</b>MTA2 is highly expressed in the primary lesions of gastric cancer than that in adjacent non-cancerous tissues, and is closely related with tumor invasion. MTA2 expression is elevated in Sp1 positive gastric cancer.</p>


Subject(s)
Female , Humans , Male , Middle Aged , Gene Expression Regulation, Neoplastic , Histone Deacetylases , Genetics , Metabolism , Neoplasm Invasiveness , Neoplasm Staging , RNA, Messenger , Metabolism , Repressor Proteins , Genetics , Metabolism , Sp1 Transcription Factor , Metabolism , Stomach Neoplasms , Metabolism , Pathology
8.
Chinese Journal of Gastrointestinal Surgery ; (12): 99-102, 2012.
Article in Chinese | WPRIM | ID: wpr-290846

ABSTRACT

Gastric cancer remains one of the most common causes of cancer-related death in China. Radical operation is the only potentially curative therapy for advanced gastric cancer (AGC). D2 radical gastrectomy has been widely accepted as a standard surgical procedure for patients with AGC in China. Several clinical trials have revealed that more extended resection than D2 surgery has no impact on survival. In order to improve the prognosis of AGC patients, it is necessary to carry out the preoperative TNM staging for selecting a reasonable therapeutical modality before surgery. Multimodality treatment involving perioperative chemotherapy, radiotherapy or molecular targeting agents in addition to surgery have been thought to be promising treatment strategy. In this article, we present an update on the current literature regarding the trends of surgical multimodal treatment for the patients with AGC.


Subject(s)
Humans , Combined Modality Therapy , Stomach Neoplasms , General Surgery
9.
Chinese Journal of Gastrointestinal Surgery ; (12): 169-173, 2012.
Article in Chinese | WPRIM | ID: wpr-290828

ABSTRACT

<p><b>OBJECTIVE</b>To explore the interaction between SerpinB5 and MAFbx in gastric cancer cell and to identify the interaction sites.</p><p><b>METHODS</b>The interaction between SerpinB5 and MAFbx was screened and validated by yeast two-hybrid screening and co-immunoprecipitation. The expression of MAFbx was analyzed after SerpinB5 expression being modified by RNA interference and pGBKT7-SerpinB5 transfection. The impact of SerpinB5 on the expression of MAFbx was studied in gastric cancer cell line SUN-16. A model of MAFbx was constructed by homology modeling. The related residues for interaction were analyzed by Autodock4.0.</p><p><b>RESULTS</b>The interaction between SerpinB5 and MAFbx was validated. The expression of MAFbx changed along with SerpinB5 expression. Amino acids including PRO261, ASN361, and LYS362 were key residue in the interaction of SerpinB5 and MAFbx.</p><p><b>CONCLUSION</b>SerpinB5 interacts with MAFbx in gastric cancer cell. Amino acids including PRO261, ASN361, and LYS362 are potential binding sites.</p>


Subject(s)
Humans , Cell Line, Tumor , Immunoprecipitation , Muscle Proteins , Genetics , Metabolism , RNA Interference , SKP Cullin F-Box Protein Ligases , Genetics , Metabolism , Serpins , Genetics , Metabolism , Stomach Neoplasms , Genetics , Metabolism , Two-Hybrid System Techniques
10.
Chinese Journal of Gastrointestinal Surgery ; (12): 180-184, 2012.
Article in Chinese | WPRIM | ID: wpr-290826

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the effects of Bevacizumab on the tumor growth, proliferation and apoptosis of gastric cancer xenograft, and the impacts on the VEGF and Sp1 expression.</p><p><b>METHODS</b>Gastric cancer xenografts in nude mice were established using SGC-7901 gastric cancer cell line. The nude mice were randomly divided into two groups, Bevacizumab treatment group and PBS group. The tumor sizes were measured for tumor growth curve. The proliferation and angiogenesis were evaluated by immunohistochemistry (IHC) staining of Ki67 and CD34. TUNEL assay was used for apoptosis evaluation. The expression of VEGF and Sp1 in tumor cells were detected by IHC and Western blot.</p><p><b>RESULTS</b>Compared to the PBS group, the tumor growth decreased significantly (P<0.05), the proliferation of tumor cells and angiogenesis decreased, and apoptosis index increased significantly [(5.3 ± 1.8)% vs. (16.7 ± 6.7)%, P<0.01] in Bevacizumab group. The results of IHC and Western blot demonstrated that the expression of VEGF and the microvessel density (MVD) was decreased (4.0 ± 1.0 vs. 16.3 ± 1.5, P<0.001) in Bevacizumab treatment group. No obvious changes of Sp1 expression were observed in Bevacizumab treatment group.</p><p><b>CONCLUSIONS</b>Bevacizumab can inhibit the growth of gastric cancer xenografts in nude mice, decrease the VEGF expression and MVD. However, the compensatory up-regulation of transcription factor Sp1 is not affected by Bevacizumab.</p>


Subject(s)
Animals , Humans , Mice , Antibodies, Monoclonal, Humanized , Pharmacology , Apoptosis , Bevacizumab , Gene Expression Regulation, Neoplastic , Mice, Nude , Sp1 Transcription Factor , Metabolism , Stomach Neoplasms , Metabolism , Pathology , Vascular Endothelial Growth Factor A , Metabolism , Xenograft Model Antitumor Assays
11.
Chinese Journal of Gastrointestinal Surgery ; (12): 388-391, 2012.
Article in Chinese | WPRIM | ID: wpr-290777

ABSTRACT

<p><b>OBJECTIVE</b>To identify novel multi-drug resistance-related genes, and to explore the mechanisms of multi-drug resistance.</p><p><b>METHODS</b>Multi-drug resistant cell line Lovo/5-FU was established by incubation with increasing dose of 5-FU. The sensitivity to 5-FU and cis-diaminodichloroplatinum (CDDP) was measured by MTT assay. Two dimensional electrophoresis plus mass spectrum(2-DE/MS) was used to identify the differentially expressed protein between Lovo and Lovo/5-FU. The identified protein was then verified by Western blot analysis.</p><p><b>RESULTS</b>The IC50 concentrations of Lovo/5-FU to 5-FU and CDDP were increased by 31 and 3 times, compared with Lovo (both P<0.01). 2DE-MS showed that CAP-G and RhoGDI2 were up-regulated, whereas 6-PGL, DCI, Prdx-6 and Maspin were down-regulated in Lovo/5-FU. Western blot analysis confirmed that the expression levels of RhoGDI2 and CAP-G in Lovo/5-FU were increased by 6.14 and 2.98 fold respectively (both P<0.01), whereas Maspin was decreased to 5.2% of Lovo(P<0.01).</p><p><b>CONCLUSIONS</b>Multi-gene and multi-pathway are involved in the development of multi-drug resistance of colorectal cancer cells. CAP-G, RhoGDI2 and Maspin are potential multi-drug resistant genes.</p>


Subject(s)
Humans , Cell Line, Tumor , Colonic Neoplasms , Genetics , Drug Resistance, Multiple , Genetics , Drug Resistance, Neoplasm , Genetics , Microfilament Proteins , Genetics , Nuclear Proteins , Genetics , Serpins , Genetics , rho Guanine Nucleotide Dissociation Inhibitor beta , Genetics
12.
Chinese Journal of Gastrointestinal Surgery ; (12): 5-7, 2011.
Article in Chinese | WPRIM | ID: wpr-237180

ABSTRACT

The rapid progress in surgery in China has been closely related to government investment in public health care, construction of medical talents team, and basic and clinical research. The achievements of bench studies promote the development of clinical surgery. Translational medicine (bench-bedside-bench) has gained much attention in the medical community. The driving force promoting long-term development of surgery in China includes collaboration of basic scientists and surgeons, cultivation of surgeons with aptitude in scientific research, initiation of clinical research and popularization of multidisciplinary team.


Subject(s)
Humans , Biomedical Research , China , General Surgery
13.
Chinese Journal of Pathology ; (12): 475-479, 2011.
Article in Chinese | WPRIM | ID: wpr-261750

ABSTRACT

<p><b>OBJECTIVE</b>To establish experimental models for tumor neovascularization and to apply quantitative digital imaging analysis in the study.</p><p><b>METHODS</b>An endothelial tube formation model was established by human umbilical vein endothelial cells (HUVECs). A vasculogenic mimicry model was established by SGC-7901 gastric cancer cell line. Fertilized eggs were used to establish a chorioallantoic membrane angiogenesis model. Using gene transfection experiment, IRX1 tumor suppressor gene was chosen as a therapeutic target. Image Pro Plus (IPP) analysis software was used for digital vascular images analysis with parameters including points, lines, angles and integral absorbance (IA) for the tubular formation or vasculogenic mimicry.</p><p><b>RESULTS</b>Digital image analysis by IPP showed that HUVEC tubular formation was significantly inhibited in IRX1 transfectant, compared with controls. The tubular numbers in three groups were 12.80 +/- 3.83, 29.00 +/- 5.34 and 28.20 +/- 4.32 (P<0.01). The connection points of tubules in three groups were 13.20 +/- 2.59, 25.00 +/- 2.24 and 24.60 +/- 3.21 (P<0.01). The tubular lengths of three groups were (821.5 +/- 12.5), (930.9 +/- 13.5) and (948.4 +/- 18.1) microm (P=0.022). The IA values of PAS stain in three groups were 3606 +/- 363, 14 200 +/- 1251 and 15 043 +/- 1220 (P<0.01). In chick chorioallantoic membrane model, the angular numbers of tubules in three groups were 6.41 +/- 2.60, 10.27 +/- 2.65 and 9.18 +/- 1.99 (P<0.01).</p><p><b>CONCLUSIONS</b>The endothelial tube formation model, vasculogenic mimicry model and chorioallantoic membrane angiogenesis model are useful for gene therapy and drug screening with targeting neoplastic vascularization. Professional image analysis software may greatly facilitate the quantitative analysis of tumor neovascularization.</p>


Subject(s)
Animals , Humans , Cell Line, Tumor , Cells, Cultured , Chorioallantoic Membrane , Diagnostic Imaging , Methods , Homeodomain Proteins , Genetics , Metabolism , Physiology , Human Umbilical Vein Endothelial Cells , Neovascularization, Pathologic , Neovascularization, Physiologic , Software , Stomach Neoplasms , Genetics , Metabolism , Pathology , Transcription Factors , Genetics , Metabolism , Physiology , Transfection
14.
Chinese Journal of Pathology ; (12): 436-441, 2010.
Article in Chinese | WPRIM | ID: wpr-333225

ABSTRACT

<p><b>OBJECTIVE</b>To analyze microarray datasets deposited in the public database and to identify TNM associated genes in gastric cancers.</p><p><b>METHODS</b>Microarray datasets of gastric cancer were selected from GEO database. Differentially expressed genes related to TNM staging were evaluated by significant analysis of the microarray using MultiExperiment Viewer (MEV) platform. Candidate gene expressions in gastric cancer tissues and cell lines were verified by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative RT-PCR, Western blot and immunohistochemistry.</p><p><b>RESULTS</b>GES4007 dataset was re-analyzed leading to the identification of 14 genes associated with TNM staging. Over-expression of matrix gla protein (MGP) was confirmed in gastric cancer cell lines and tumor tissues by quantitative RT-PCR, Western blot and immunohistochemistry. Increased MGP expression was found in 22 of 54 cases of (40.7%) gastric cancer specimens compared to the normal gastric tissues. The up-regulation of MGP mRNA expression closely correlated with TNM stage (P = 0.001) and prognosis (P = 0.006).</p><p><b>CONCLUSIONS</b>Public databases of microarray studies are the valuable resources for data mining. MGP has been identified and confirmed as a novel biomarker for the TNM stage and prognosis of gastric cancer.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Biomarkers, Tumor , Genetics , Metabolism , Calcium-Binding Proteins , Genetics , Cell Line, Tumor , Extracellular Matrix Proteins , Genetics , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Lymphatic Metastasis , Neoplasm Staging , Oligonucleotide Array Sequence Analysis , RNA, Messenger , Metabolism , Stomach Neoplasms , Genetics , Metabolism , Pathology , Survival Rate , Up-Regulation
15.
Chinese Journal of Gastrointestinal Surgery ; (12): 899-902, 2010.
Article in Chinese | WPRIM | ID: wpr-237193

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate laparoscopic radical gastrectomy for early gastric cancer.</p><p><b>METHODS</b>A total of 204 patients with early gastric cancer undergoing laparoscopic-assisted radical gastrectomy or open radical gastrectomy between October 2004 and December 2009 were retrospectively reviewed and analyzed. Patients were divided into laparoscopic group(LAP, n=78) and open group (OPEN, n=126). Operative time, blood loss, time to passage of flatus, postoperative hospital stay, complications and pathologic findings were compared between the two groups.</p><p><b>RESULTS</b>Compared to the OPEN group, operative time in the LAP group was significantly shorter[(202.9±45.6) min vs.(219.8±45.2) min, P<0.05], blood loss was less[(144.5±146.5) ml vs. (245.0±146.4) ml, P<0.05], time to passage of flatus was shorter[(3.1±1.1) d vs.(4.5±1.6) d, P<0.05], postoperative hospital stay was shorter[(10.8±1.2) d vs. (12.4±3.8) d, P<0.05]. However, the two groups were comparable with regard to postoperative complication rate(10.3% vs. 12.7%, P>0.05), proximal resection margin[(4.0±1.9) cm vs. (4.2±1.7) cm, P>0.05], distal resection margin [(3.6±1.7) cm vs. (3.5±1.8) cm, P>0.05], number of harvested lymph node(13.1±6.5 vs. 14.5±8.2, P>0.05). The median follow up was 22(2-64) months. There were no tumor recurrences or metastases in the LAP group. In the OPEN group, only 1 patient died from peritoneal metastasis. Total hospital costs between the two groups were similar(P>0.05).</p><p><b>CONCLUSION</b>Laparoscopic radical gastrectomy is a safe, feasible, effective, and less invasive surgery for early gastric cancer.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Follow-Up Studies , Gastrectomy , Methods , Laparoscopy , Laparotomy , Lymph Node Excision , Retrospective Studies , Stomach Neoplasms , General Surgery , Treatment Outcome
16.
Chinese Medical Journal ; (24): 3193-3199, 2010.
Article in English | WPRIM | ID: wpr-241608

ABSTRACT

<p><b>BACKGROUND</b>Genetic modification of dendritic cells (DCs) has been used as an effective approach to enhance anti-tumor immunity. RNA interference (RNAi), which can cause the degradation of any RNA in a sequence-specific manner, is a post-transcriptional gene silencing mechanism. In this study, small-interfering RNA (siRNA) specific for the Ii gene was transfected into DCs, and the anti-tumor immunity of Ii-silenced DCs was assessed.</p><p><b>METHODS</b>The silencing effect of siRNA was evaluated by Western blotting and real-time PCR analyses. In vitro cytotoxic activity of T cells was evaluated using a Cytotox 96(®) non-radioactive cytotoxicity assay kit. The time to tumor onset and the tumor volumes were used as reliable indices to assess the anti-tumor immunity in vivo. To further examine the mechanisms underlying the anti-tumor immunity, flow cytometry analysis was used.</p><p><b>RESULTS</b>The Ii expression of DCs was significantly reduced after Ii siRNA transfection. Significant in vitro anti-tumor ability was exhibited when DCs were co-transfected with Ii siRNA plus endogenous tumor antigen (P < 0.05). Furthermore, tumor growth was greatly inhibited when mice were immunized with DCs transfected with Ii siRNA plus tumor antigen prior to or subsequent to tumor implantation. Flow cytometry analysis in vitro and in vivo indicated that both CD4(+) and CD8(+) T cells were significantly activated in the Ii siRNA group (P < 0.05).</p><p><b>CONCLUSION</b>Silencing of the Ii gene of DCs may offer a potential approach to enhance DC-based anti-tumor immunity.</p>


Subject(s)
Animals , Female , Mice , Antigens, Differentiation, B-Lymphocyte , Genetics , Metabolism , Blotting, Western , Cells, Cultured , Dendritic Cells , Allergy and Immunology , Metabolism , Flow Cytometry , Gene Silencing , Physiology , Histocompatibility Antigens Class II , Genetics , Metabolism , Neoplasms , Allergy and Immunology , RNA Interference , Physiology , RNA, Small Interfering , Genetics , Physiology , Reverse Transcriptase Polymerase Chain Reaction
17.
Chinese Journal of Gastrointestinal Surgery ; (12): 106-110, 2010.
Article in Chinese | WPRIM | ID: wpr-259327

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the value of multidetector-row computed tomography (MDCT) in preoperatively predicting peritoneal metastasis of gastric cancer and to evaluate the indication for laparoscopic staging of gastric cancer on the basis of MDCT features.</p><p><b>METHODS</b>Six hundred and forty gastric cancer patients underwent preoperative MDCT examination, and the results of MDCT were compared with surgical and pathological findings. In addition, the relationship between MDCT features (depth of invasion, lymph node metastasis status, tumor size, and thickness of tumor) and peritoneal metastasis of gastric cancer was analyzed.</p><p><b>RESULTS</b>The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCT in predicting peritoneal metastasis of gastric cancer were 51.0% (25/49), 99.3% (587/591), 86.2% (25/29), 96.1% (587/611), and 95.6% (612/640), respectively. Univariable analysis showed that all the four MDCT features (depth of invasion, lymph node metastasis status, tumor size, and tumor thickness) of gastric cancer were significantly correlated with the peritoneal metastasis of gastric cancer. None of the patients diagnosed with stage T(0~2)N(x)M(0) or T(x)N(0)M(0) gastric cancer by MDCT were found to have peritoneal metastasis. Receiver operating characteristic (ROC) analysis showed that the accuracy of the tumor size and thickness of gastric cancer in determining peritoneal metastasis was high(area under ROC curve was 0.83 and 0.75, respectively). Multivariable analysis showed that only tumor size was significantly correlated with the peritoneal metastasis from gastric cancer.</p><p><b>CONCLUSIONS</b>The clinical value of MDCT in preoperative prediction of peritoneal metastasis from gastric cancer is favorable. Laparoscopy can be avoided in patients with small tumor size or stage T(0~2)N(x)M(0) or T(x)N(0)M(0) gastric cancer diagnosed by MDCT due to lower incidence of peritoneal metastasis.</p>


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Neoplasm Metastasis , Neoplasm Staging , Methods , Peritoneal Neoplasms , Diagnostic Imaging , Predictive Value of Tests , Sensitivity and Specificity , Stomach Neoplasms , Diagnostic Imaging , Pathology , Tomography, X-Ray Computed , Methods
18.
Chinese Journal of Gastrointestinal Surgery ; (12): 111-114, 2010.
Article in Chinese | WPRIM | ID: wpr-259326

ABSTRACT

<p><b>OBJECTIVE</b>To compare the efficacy of modified D(2) radical total gastrectomy with spleen-preserving and D(2) radical total gastrectomy with splenectomy in patients with gastric cancer located in the upper third, upper and middle third and entire stomach.</p><p><b>METHODS</b>One hundred and twelve patients with gastric cancer in the upper third, upper and middle third, or entire stomach underwent radical total gastrectomy between January 1989 and December 1994. Modified D(2) total radical gastrectomy with spleen-preserving (spleen-preservation group) was performed in 61 patients, and 51 underwent D(2) total radical gastrectomy with splenectomy (splenectomy group). The differences in clinicopathological characteristics,5-year survival rate, incidence of postoperative complication and hospital stay between the two groups were analyzed retrospectively.</p><p><b>RESULTS</b>There were no significant differences between the spleen-preservation group and the splenectomy group in gender, age, tumor size, T stage, N stage and TNM stage. The overall 5-year survival rate was 41.0% in the spleen-preservation group and 39.2% in the splenectomy group (P>0.05). The 5-year survival rates of patients with stage I, II, III and IIII were 100%, 66.7%, 27.8% and 17.4% in the spleen-preservation group, respectively, and were 100%, 70.0%, 26.7% and 5.6% in the splenectomy group, respectively (all P>0.05). The incidence of postoperative complication was lower in the spleen-preservation group (11.5% vs 27.5%, P<0.05). The mean hospital stay was longer in the splenectomy group (27.3 d vs 20.3 d, P=0.057).</p><p><b>CONCLUSION</b>The efficacy of modified D(2) radical total gastrectomy with spleen-preserving for patients with gastric cancer in the upper third, upper and middle third or entire stomach is similar to that of D(2) radical total gastrectomy with splenectomy, and the spleen-preserving procedure is associated with decreased postoperative complication and improved survival.</p>


Subject(s)
Aged , Female , Humans , Middle Aged , Gastrectomy , Lymph Node Excision , Neoplasm Staging , Prognosis , Splenectomy , Stomach Neoplasms , Pathology , General Surgery , Survival Rate , Treatment Outcome
19.
Chinese Journal of Gastrointestinal Surgery ; (12): 177-180, 2010.
Article in Chinese | WPRIM | ID: wpr-259315

ABSTRACT

<p><b>OBJECTIVE</b>To assess the efficacy and safety of docetaxel plus oxaliplatin and capecitabine (DOX) in the treatment of advanced gastric adenocarcinoma.</p><p><b>METHODS</b>A total of 30 patients were recruited to receive DOX regimen (docetaxel 75 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, and capecitabine 1000 mg/m(2) bid d1-14, repeated every 3 weeks). Only those who completed at least 2 cycles were assessed.</p><p><b>RESULTS</b>The number of patients with complete response, partial response, stable disease and progressive disease were 1, 2, 25 and 2, respectively. The objective response rate was 10.0%(3/30) and the disease control rate was 93.3%(28/30). After a median follow-up of 261 days, the median progression free survival and overall survival time were 197 days and 466 days, respectively. The most common grade III to IV toxicity was hematologic toxicity. The percentage of patients with grade III to IV leucopenia, neutropenia and febrile neutropenia were 60.0%, 43.3% and 30.0%, respectively. The most common grade III to IV non-hematologic toxicity was fatigue, nausea, vomiting, anorexia, diarrhea, and hand-foot syndrome.</p><p><b>CONCLUSIONS</b>DOX regimen demonstrates promising efficacy in the treatment of advanced gastric adenocarcinoma. The associated toxicity can be well tolerated and controlled. Large scale clinical trial is necessary to obtain further evidence.</p>


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma , Drug Therapy , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Capecitabine , Deoxycytidine , Fluorouracil , Organoplatinum Compounds , Stomach Neoplasms , Drug Therapy , Taxoids , Treatment Outcome
20.
Chinese Journal of Gastrointestinal Surgery ; (12): 846-850, 2010.
Article in Chinese | WPRIM | ID: wpr-266259

ABSTRACT

<p><b>OBJECTIVE</b>To clone core promoter regions of iroquois homeobox gene 1 (IRX1) gene and evaluate the regulatory mechanism of IRX1 transcription.</p><p><b>METHODS</b>Upstream sequence from transcriptional start site was predicted using bioinformatics methods. Serial deleted fragments from IRX1 promoter sequences were amplified by PCR and luciferase reporter plasmids were constructed. The luciferase intensity was analyzed after transferring reporters into GES-1 gastric mucosa cell line.</p><p><b>RESULTS</b>The promoter of IRX1 was predicted to be within 700 bp from the 5'-flanking region of IRX1 gene. Eight serial deleted luciferase reporter plasmids were constructed. The transcriptional activity of different fragments was expressed as following: p-416>p-584>p-715>p-350>p-687>p-320>p-188>p-92. Except p-320 and p-188, the transcriptional activity of other 6 fragments was higher than that of PGL3-basic plasmid. The transcriptional activity was the highest in p-416 and decreased sharply from p-320 to p-188.</p><p><b>CONCLUSIONS</b>The fragment p-416 shows the strongest promoter activity. The sequence from -320 bp to -188 bp is identified as core promoter region, which is focused as key sequence for further regulatory analysis, since some binding sites for important transcriptional factors such as Sp1 and TFII D are predicted.</p>


Subject(s)
Humans , Cell Line , Cloning, Molecular , Gastric Mucosa , Cell Biology , Genes, Homeobox , Homeodomain Proteins , Genetics , Promoter Regions, Genetic , Transcription Factors , Genetics
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