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1.
Sci Total Environ ; 945: 174093, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38906307

ABSTRACT

Black carbon (BC) and brown carbon (BrC) over the high-altitude Tibetan Plateau (TP) can significantly influence regional and global climate change as well as glacial melting. However, obtaining plateau-scale in situ observations is challenging due to its high altitude. By integrating reanalysis data with on-site measurements, the spatial distribution of BC and BrC can be accurately estimated using the random forest algorithm (RF). In our study, the on-site observations of BC and BrC were successively conducted at four sites from 2018 to 2021. Ground-level BC and BrC concentrations were then obtained at a spatial resolution of 0.25° × 0.25° for three periods (including Periods-1980, 2000, and 2020) using RF and multi-source data. The highest annual concentrations of BC (1363.9 ± 338.7 ng/m3) and BrC (372.1 ± 96.2 ng/m3) were observed during Period-2000. BC contributed a dominant proportion of carbonaceous aerosol, with concentrations 3-4 times higher than those of BrC across the three periods. The ratios of BrC to BC decreased from Period-1980 to Period-2020, indicating the increasing importance of BC over the TP. Spatial distributions of plateau-scale BC and BrC concentrations showed heightened levels in the southeastern TP, particularly during Period-2000. These findings significantly enhance our understanding of the spatio-temporal distribution of light-absorbing carbonaceous aerosol over the TP.

2.
Huan Jing Ke Xue ; 44(10): 5382-5391, 2023 Oct 08.
Article in Chinese | MEDLINE | ID: mdl-37827756

ABSTRACT

Air pollution continues to be a serious problem in Xi'an. A heavy pollution process and formation mechanism were investigated in Xi'an in January 2019 using multi-source methods (such as material balance and sulfur/nitrogen oxidation rate (SOR/NOR)). The multi-source data included the concentrations of PM2.5, PM10, SO2, NO2, CO, and O3; the chemical components of PM2.5; the meteorological records of ground and vertical observations; the atmospheric reanalysis data. Three phases were obtained including the accumulation phase (P1), maintenance phase (P2), and dispersion phase (P3) during the pollution period. The pollution event was primarily attributed to the superposition of adverse weather conditions and feedback effects. During the periods of P1 and P2, the area of Xi'an was affected by blocking and zonal westerly airflow at 500 hPa (with flat westerly airflow) and uniform-distribution pressure at sea level with a limited pressure gradient and stable weather conditions, and the easterly wind was dominant at 925 hPa; not all of these factors were conducive to the pollutant diffusion. An interaction feedback mechanism between meteorological conditions and heavy pollution could be studied using the ground-based microwave radiometer. The correlations between PM2.5 and inversions of water vapor density, relative humidity, air temperature, and temperature inversion were significant with coefficients of 0.86, 0.62, 0.53, and 0.38, respectively. The feedback mechanism was primarily manifested as follows:with the pollutant accumulation, the radiative cooling effect could lead to or strengthen the occurrence and intensity of temperature inversion, decrease the mixed layer height, and cause moisture accumulation. High humidity could further maintain the pollution by accelerating the secondary formation and promoting the hygroscopic growth of aerosol particles. Therefore, the dominant chemical components to PM2.5were secondary inorganic ions (SO42-+NO3-+NH4+, SNA) and "other" components during the period of P2, with contributions of 43.2% and 23.1%, respectively. In addition, the peak values of PM2.5, SOR, NOR, and the light extinction coefficients all occurred on the same days (January 3 and 6), indicating that the effect of secondary formation was important for both heavy pollution events and visibility. The total contribution of NH4NO3, organic matter (OM), (NH4)2SO4, and EC to the light extinction coefficient was more than 85%. Limited variations in the proportion for components were observed in three phases. During the period of P3, the strong cold air in the mid-lower atmosphere was conducive to the dry and clean air sinking and the pressure gradient at sea level increasing. These were beneficial to the diffusion of air pollutants and water vapor.

3.
Tumour Biol ; 37(3): 3905-11, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26476541

ABSTRACT

An elevated serum albumin (ALB) and albumin/globulin ratio (AGR) have been reported to be associated with a favorable prognosis for several types of cancer. However, little is known about prognostic significance of globulin (GLB) in gastric cancer patients. The purpose of this study was to evaluate whether GLB, ALB, and AGR analysis could predict the prognosis of patients with gastric cancer. A retrospective cohort of 186 patients with gastric cancer followed by radical surgery was recruited between January 2007 and December 2010. Levels for preoperative GLB and ALB were obtained and used to calculate the AGR. Survival analysis was used to evaluate the predictive value of GLB, ALB, and AGR. X-tile program determined 37.6, 33.4, and 1.33 as the optimal cutoff value for ALB, GLB, and AGR in terms of survival. Univariate analysis revealed that low GLB levels were significantly associated with favorable survival (P = 0.045). Conversely, low ALB levels were associated with a significantly worse survival (P = 0.000). In conclusion, low preoperative GLB level may serve as a valuable marker to predict the prognosis of gastric cancer patients.


Subject(s)
Biomarkers, Tumor/blood , Serum Albumin/analysis , Serum Globulins/analysis , Stomach Neoplasms/blood , Adult , Aged , Aged, 80 and over , Humans , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Preoperative Period , Prognosis , Retrospective Studies , Sex Hormone-Binding Globulin/analysis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgery , Young Adult , alpha-Macroglobulins/analysis
4.
Eur J Cancer ; 50(10): 1772-1778, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24768330

ABSTRACT

OBJECTIVES: For advanced gastrointestinal stromal tumour (GIST) patients who are responding to imatinib mesylate, the role of surgery has not been formally demonstrated. This multicenter randomised controlled trial was designed to assess whether surgery to treat residual disease for patients with recurrent/metastatic GISTs responding to imatinib mesylate (IM) improved progression free survival (PFS) compared with IM treatment alone. METHODS: Between 3 and 12months after starting IM for recurrent/metastatic GISTs, eligible patients were randomised to two arms: Arm A (surgery for residual disease) and Arm B (IM treatment alone). In Arm A (19pts), surgery was performed to remove residual macroscopic lesions as completely as possible, and IM treatment continued after surgery. In Arm B (22pts), IM was given alone at a dose of 400mg per day until disease progression. The primary end-point was PFS measured from the date IM started. This study was registered in the ChiCTR registry with the ID number ChiCTR-TRC-00000244. RESULTS: This randomised trial was closed early due to poor accrual. Only 41 patients were enrolled as opposed to 210 patients planned. 2-year PFS was 88.4% in the surgery arm and 57.7% in the IM-alone arm (P=0.089). Median overall survival (mOS) was not reached in the surgery arm and 49months in patients with IM-alone arm (P=0.024). CONCLUSIONS: While no significant differences were observed in the two arms, this study suggests that surgical removal of the metastatic lesion may improve the outcome of advanced GIST patients and should stimulate additional research on this topic.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/surgery , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/surgery , Metastasectomy , Neoplasm Recurrence, Local , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Antineoplastic Agents/adverse effects , Benzamides/adverse effects , Chemotherapy, Adjuvant , China , Disease Progression , Disease-Free Survival , Early Termination of Clinical Trials , Female , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/secondary , Humans , Imatinib Mesylate , Kaplan-Meier Estimate , Male , Metastasectomy/adverse effects , Metastasectomy/mortality , Middle Aged , Neoadjuvant Therapy , Neoplasm, Residual , Patient Selection , Piperazines/adverse effects , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Sample Size , Time Factors , Treatment Outcome
5.
Am J Surg ; 207(6): 847-54, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24119719

ABSTRACT

BACKGROUND: Prognostic factors and optimal management of desmoid tumors have been discussed for decades. The authors present the results of a large series of patients with desmoid tumors treated at a single institution to investigate the prognostic factors influencing event-free survival (EFS) and suitable treatments for these rare tumors. METHODS: Two hundred fourteen patients with desmoid tumors admitted to the surgical department were included, of whom 20 were recommended for a policy of watchful waiting. The following clinical parameters were studied: admission status, age, sex, tumor site, tumor size, margin status, and therapeutic strategy. Univariate and multivariate analysis were performed for EFS. RESULTS: Forty-two patients had local recurrence. One patient died of intra-abdominal disease. The 5-year and 10-year EFS rates were 78.8% and 77.9%, respectively. In univariate analysis, admission status, tumor site, tumor size, and group (R0 vs R1 and R0 vs R2) had significant impacts on EFS. EFS discrepancy was not significant between R1 and R2 or biopsy groups. In multivariate analysis, tumor size and admission status had independent value. The median delay to progression for patients undergoing watchful waiting was comparable with that for the surgical group. CONCLUSIONS: This study demonstrates that tumor size and a history of recurrence are independent predictors of EFS. Surgery is warranted if it can be R0 and function sparing. Nonsurgical modalities or a policy of watchful waiting may be a better choice for unresectable disease.


Subject(s)
Fibromatosis, Aggressive/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Child , Combined Modality Therapy , Disease Progression , Disease-Free Survival , Female , Fibromatosis, Aggressive/mortality , Fibromatosis, Aggressive/pathology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Risk Factors
6.
Oncol Rep ; 30(6): 2777-84, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24126887

ABSTRACT

Our previous findings revealed that FGFR4 may be a novel therapeutic target for gastric cancer. The aim of the present study was to explore the effects of a combination of PD173074 (PD) and 5-fluorouracil (5-Fu) on the biological behavior of gastric cancer cell lines and the relevant mechanisms involved. MKN45, a gastric cancer cell line, was treated with each single agent alone or a combination of FGF19, PD and 5-Fu. Then, a series of functional assays were performed using CCK-8 assay and flow cytometry. Western blot analysis was used to determine the expression of signaling pathway and downstream-related molecules in the MKN45 cells following the different treatments. As the concentration of PD and 5-Fu increased, the cell viability gradually decreased; the viability of the combination group was less than the viability following single administration. Western blot analysis showed that FGFR4 expression was weak in the 5-Fu-treated groups when compared with the control. PD markedly increased the apoptosis rate of MKN45 cells when compared to the control; the apoptosis rate in the cells treated with the combination of PD and 5-Fu was higher than that in the cells following single treatment. Furthermore, PD reduced the expression of p-ERK and Bcl-xl and increased caspase-3 expression. Inhibition of the activity of FGFR4 may be the main mechanisms of PD effect while 5-Fu reduced FGFR4 expression. Furthermore, the effects of the combination of 5-Fu and PD in inhibiting proliferation, increasing apoptosis and arresting cell cycle were superior to these effects following the single agent treatments, suggesting that the two drugs applied in combination may contribute to the effective treatment of gastric cancer.


Subject(s)
Cell Proliferation/drug effects , Fluorouracil/pharmacology , Pyrimidines/pharmacology , Receptor, Fibroblast Growth Factor, Type 4/genetics , Stomach Neoplasms/drug therapy , Apoptosis/drug effects , Caspase 3/biosynthesis , Caspase 3/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Receptor, Fibroblast Growth Factor, Type 4/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 4/biosynthesis , Signal Transduction/drug effects , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , bcl-X Protein/biosynthesis
7.
World J Gastroenterol ; 18(27): 3610-6, 2012 Jul 21.
Article in English | MEDLINE | ID: mdl-22826628

ABSTRACT

AIM: To determine the prognostic value of lymphatic and/or blood vessel invasion (LBVI) in patients with stage II gastric cancer. METHODS: From January 2001 to December 2006, 487 patients with histologically confirmed primary gastric adenocarcinoma were diagnosed with stage II gastric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node (LN) dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathological findings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure (subtotal resection vs total resection), and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS: The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years (range: 23-88 years). The 5-year overall survival rates were 50.7% and the median survival time was 62 mo. Stage IIa cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three T1N2, and stage IIb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one T1N3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% (51/269) and 42.5% (71/167) in LN-negative and LN-positive patients, respectively. In 218 patients (50.0%), there was neither a histopathologically detectable LBVI nor LN metastases (LBVI(-)/LN(-), group I); in 51 patients (11.7%), LBVI with no evidence of LN metastases was detected (LBVI(+)/LN(-), group II). In 167 patients (38.3%), LN metastases were found. Among those patients, LBVI was not determined in 96 patients (22.0%) (LBVI(-)/LN(+), group III), and was determined in 71 patients (16.3%) (LBVI(+)/LN(+), group IV). Correlation analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI (P < 0.001). The overall 5-year survival was significantly longer in LN-negative patients compared with LN-positive patients (56.1% vs 42.3%, P = 0.015). There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI-negative tumors (39.6% vs 54.8%, P = 0.006). Overall 5-year survival rates in each group were 58.8% (I), 45.8% (II), 45.7% (III) and 36.9% (IV), and there was a significant difference in overall survival between the four groups (P = 0.009). Multivariate analysis in stage II gastric cancer patients revealed that LBVI independently affected patient prognosis in LN-negative patients (P = 0.018) but not in LN-positive patients (P = 0.508). CONCLUSION: In LN-negative stage II gastric cancer patients, LBVI is an additional independent prognostic marker, and may provide useful information to identify patients with poorer prognosis.


Subject(s)
Adenocarcinoma/pathology , Blood Vessels/pathology , Lymphatic Vessels/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/surgery , Aged , Female , Gastrectomy , Humans , Kaplan-Meier Estimate , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Neoplasm Staging , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Risk Factors , Stomach Neoplasms/surgery , Time Factors , Treatment Outcome
8.
Zhonghua Wei Chang Wai Ke Za Zhi ; 15(3): 225-7, 2012 Mar.
Article in Chinese | MEDLINE | ID: mdl-22454163

ABSTRACT

Currently, the treatment of recurrent or metastatic gastrointestinal stromal tumor(GIST) has become a tremendous challenge. Some international clinical trials revealed that imatinib might significantly improve the survival of patients with recurrent or metastatic GIST. Though the combination of surgery and imatinib has become an ideal treatment of metastatic GIST, there still exist some controversies regarding how to combine the two methods. Imatinib may influence the blood coagulation mechanism, therefore it is suggested that imatinib cessation should be performed a week before operation. Cytoreductive surgery has some clinical effects on recurrent or metastatic GIST, which can be combined with targeted therapy. Furthermore, the clinical trial for recurrent or metastatic GIST needs further evaluation.


Subject(s)
Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/surgery , Benzamides/administration & dosage , Benzamides/therapeutic use , Combined Modality Therapy , Humans , Imatinib Mesylate , Piperazines/administration & dosage , Piperazines/therapeutic use , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use
9.
J Surg Oncol ; 105(3): 323-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22271501

ABSTRACT

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the prognosis of stage I gastric cancer and to compare clinicopathologic characteristics by subgroup. METHODS: Between January 2000 and December 2006, 384 patients with gastric cancer were reclassified as stage I according to the seventh edition classification. A comparative analysis was performed between three subgroups. Univariate and multivariate analyses were conducted. RESULTS: The 5-year overall survival rates in T1N0, T1N1, and T2N0 were 98.8%, 94.1%, 91.1%, respectively (P = 0.009). In patients with T2N0 gastric cancer, tumors in the upper third and larger tumors were more common than in patients with T1N0 and T1N1 gastric cancer (P < 0.001). In patients with T1N1 and T2N0 gastric cancer, the presence of lymphatic and/or blood vessel invasion (LBVI) and perineural invasion (PNI) were more common than in patients with T1N0 gastric cancer (P < 0.001). Univariate analysis showed tumor stage, depth of invasion, LBVI, and PNI were significant prognostic factors. However, multivariate analysis demonstrated that only tumor stage, LBVI, and PNI were significant variables. CONCLUSIONS: Survival data support the accuracy of new TNM classification for stage I gastric cancer. Tumor stage, the presence of LBVI and PNI are important independent prognostic factors in stage I gastric cancer.


Subject(s)
Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness , Peripheral Nervous System Neoplasms/pathology , Prognosis , Stomach Neoplasms/surgery , Vascular Neoplasms/pathology , Young Adult
11.
Zhonghua Zhong Liu Za Zhi ; 34(12): 899-904, 2012 Dec.
Article in Chinese | MEDLINE | ID: mdl-23336375

ABSTRACT

OBJECTIVE: To investigate the prognostic values of HIF-1α, APE1, VEGF, and COX-2 protein expressions and their predictive value of tumor necrosis rate and prognosis in osteosarcoma, as well as their interrelationships. METHODS: Formalin-fixed paraffin-embedded tissue samples were obtained from patients with osteosarcoma. Immunohistochemical assay was performed in pre-chemotherapy samples to determine the HIF-1α, VEGF, APE1, and COX-2 protein expression levels. Hematoxylin-eosin staining was used in post-operative samples to determine the tumor necrosis rate. Univariate and multivariate analyses were used to assess the impact of protein expression on prognosis. RESULTS: Tumor tissues were obtained from 49 patients. Their median follow up was 29 months. HIF-1α was significantly correlated to every protein we tested: VEGF (P = 0.032), APE1 (P < 0.001), and COX-2 (P < 0.001). HIF-1α protein expression had a significant impact on disease free survival (P = 0.006). Expression of HIF-1α had a sensitivity of 64.7% and a specificity of 71.9% for poor pathological response (< 90% of tumor necrosis) versus good pathological response to chemotherapy (≥ 90% necrosis). CONCLUSION: Expression of HIF-1α is a predictor of tumor response to neoadjuvant chemotherapy and outcome in osteosarcoma and is correlated with VEGF, APE1, and COX-2 expression.


Subject(s)
Bone Neoplasms/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Osteosarcoma/metabolism , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Chemotherapy, Adjuvant , Child , Cyclooxygenase 2/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Osteosarcoma/drug therapy , Osteosarcoma/pathology , Vascular Endothelial Growth Factor A/metabolism , Young Adult
12.
Cancer ; 117(23): 5304-13, 2011 Dec 01.
Article in English | MEDLINE | ID: mdl-21567388

ABSTRACT

BACKGROUND: Fibroblast growth factor receptor 4 (FGFR4) belongs to the tyrosine kinase receptor family. Little is known about the effect of FGFR4 on gastric cancer (GC). Therefore, the objective of the current study was to elucidate the role of FGFR4 in the tumorigenesis and progression of GC. METHODS: FGFR4 and some common prognosis markers, including p53, neu, and proliferating cell nuclear antigen (PCNA), were detected in 71 tissue samples from patients with GC using immunohistochemical analysis. In addition, a series of functional assays were carried out using small interfering RNA (siRNA) and included proliferation assays, clone assays, and apoptosis detection. RESULTS: Cytoplasmic FGFR4 expression in GC tissues was negative (7% of samples), low (14.1% of samples), intermediate (40.8%), and high (38% of samples). FGFR4 expression was associated with lymph node status and with PCNA and neu expression (P < .05). The 5-year relative survival rate was 61.5% in patients who had GC with low FGFR4 expression but was only 42% in patients who had high FGFR4 expression (P = .058). A subgroup analysis of the patients who had high FGFR4 expression revealed that those with stage III and IV disease had a worse prognosis (P = .044). Moreover, knockdown of FGFR4 expression led to decreased proliferation and an increased rate of apoptosis in the MKN45 and SGC7901 GC cell lines (P < .05). Western blot analysis demonstrated that the expression of caspase 3 increased, whereas the expression of extra-large B-cell lymphoma (Bcl-xL) decreased in MKN45 and SGC7901 cells after FGFR4-siRNA transfection. CONCLUSIONS: FGFR4 expression in GC tissue was extremely high. The current results indicated that FGFR4 may contribute to the progression of GC by regulating proliferation and antiapoptosis, indicating that FGFR4 may be a potential, novel drug target against GC.


Subject(s)
Apoptosis , Cell Proliferation , Receptor, Fibroblast Growth Factor, Type 4/physiology , Stomach Neoplasms/pathology , Adult , Aged , Caspase 3/analysis , Disease Progression , Female , Humans , Male , Middle Aged , Proliferating Cell Nuclear Antigen/analysis , RNA, Small Interfering/genetics , Receptor, Fibroblast Growth Factor, Type 4/analysis , Receptor, Fibroblast Growth Factor, Type 4/antagonists & inhibitors
13.
Cancer Lett ; 307(2): 124-31, 2011 Aug 28.
Article in English | MEDLINE | ID: mdl-21514720

ABSTRACT

Sox17, a transcription factor, was considered as an antagonist to inhibit canonical Wnt/ß-catenin signaling in several malignant tumors. Extremely little is known about Sox17 in gastric cancer. Therefore, the aim of this study was to elucidate the vital role of Sox17 in the tumorigenesis and progression of gastric cancer. Real time PCR was used to detect the expression of Sox17 in gastric cancer tissue. Furthermore, a series of function assays, utilizing small interfering RNA (siRNA)-mediated knockdown of Sox17 expression in MKN45 gastric cancer cells, have been performed in this study, including proliferation assay, clonogenic assay, cell-cycle evaluation, apoptosis detection as well as western blot assay. Sox17 expression were low in gastric cancer tissues as compared to normal tissue (P=0.013). Knockdown of Sox17 by Sox17-siRNA markedly enhanced the proliferation ability of MKN45 cells when compared with negative siRNA-infected cells and mock group (P<0.05). Down-regulation of Sox17 contributed to increasing cloning efficiency and activating cell cycle of MKN45 cells (P<0.05). However, there was no significantly statistical difference in terms of apoptosis rate between Sox17-siRNA group and Negative or mock group. Western blot assay revealed that the expression of CyclinD1 observably increased while p27(Kip1) expression remarkably decreased in MKN45 cells with Sox17-siRNA transfection. Furthermore, apoptosis-related molecules, Caspase3 and Bcl-xl, have no dramatically discrepant expression when knockdown of Sox17 in MKN45 cells. Sox17 prominently contributes to gastric cancer progression through regulating proliferation and cell cycle, indicating a novel diagnosis and prognosis biomarker as well as a potential therapeutic target in gastric cancer.


Subject(s)
Cell Cycle/physiology , Cell Proliferation , SOXF Transcription Factors/physiology , Stomach Neoplasms/pathology , Base Sequence , Blotting, Western , DNA Primers , Disease Progression , Fluorescent Antibody Technique , Gene Knockdown Techniques , Humans , Polymerase Chain Reaction , RNA, Small Interfering , SOXF Transcription Factors/genetics
14.
J Surg Oncol ; 104(1): 76-82, 2011 Jul 01.
Article in English | MEDLINE | ID: mdl-21400534

ABSTRACT

BACKGROUND: The aim of this study was firstly to elucidate the prognosis of familial gastric cancer (FGC) in Chinese population. METHODS: A total of 162 patients were recruited, including 81 patients with FGC and 81 patients with sporadic gastric cancer (SGC), who underwent gastrectomy between 1996 and 2007. Paraffin-embedded tumor specimens were obtained from tissue bank of Cancer Hospital, Fudan University. The expression of epidermal growth factor receptor (EGFR), P53, C-myc, and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemical method. RESULTS: There were significant differences in tumor size, vessel invasion, EGFR, and P53 expression between FGC and SGC patients. The 5-year survival rates were 48% and 57% in FGC and SGC patients, respectively (P = 0.033). Subgroup analysis showed that the 5-year survival rates were worse in FGC patients with nerve invasion, high PCNA expression, negative expression of EGFR, and positive expression of P53 than those in SGC group. Multivariate analysis showed that AJCC stage, tumor size, and nerve invasion were independent prognostic factors in all patients. Furthermore, AJCC stage and P53 expression dramatically affected the prognosis of FGC patients. CONCLUSIONS: The prognosis of FGC patients might be worse than those of SGC patients. AJCC stage and P53 expression are independent prognostic factors in FGC patients.


Subject(s)
ErbB Receptors/metabolism , Genes, myc/physiology , Proliferating Cell Nuclear Antigen/metabolism , Stomach Neoplasms/epidemiology , Stomach Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Adult , Aged , Asian People/genetics , China/epidemiology , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Stomach Neoplasms/genetics , Survival Rate
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 13(8): 583-6, 2010 Aug.
Article in Chinese | MEDLINE | ID: mdl-20737309

ABSTRACT

OBJECTIVE: To evaluate the clinicopathological characteristics and prognosis of poorly differentiated neuroendocrine carcinoma of the stomach. METHODS: Twenty-three poorly differentiated neuroendocrine carcinomas of the stomach were treated in the Department of Abdominal Surgery at the Cancer Hospital, Fudan University between January 1996 and December 2007. Clinicopathological characteristics and survival data were analyzed. RESULTS: Poorly differentiated neuroendocrine carcinomas of the stomach accounted for 0.52% of all the gastric carcinomas. The tumor occurred more often in males (18 of 23), older patients (mean age of 62 years), upper third of the stomach (16 of 24,one patient had more than one lesion) with large size (mean diameter of 6.8 cm). TNM stages were as follows: stage II in 3 patients, stage III in 12, and stage IIII in 8. Thirteen patients underwent curative resection, while 8 underwent palliative resection and 2 others underwent exploratory laparotomy with biopsy. Of the 21 surgical resection specimens, vascular invasion was found in 18 patients (85.7%), perineural invasion in 16 patients (76.2%), and regional lymph node metastasis in 17 patients (81.0%). Follow up time ranged from 3 to 63 months. Mean overall survival time was 17.7 months. The 1-year, 2-year, and 5-year survival rates were 47.8%, 19.1%, and 4.3%, respectively. Statistically significant differences in survival curves were observed which were related to tumor staging and surgery type, but not related to gender, age, tumor location, or diameter. CONCLUSIONS: Poorly differentiated neuroendocrine carcinomas of the stomach are rare and with poor prognosis. Tumor stage and surgical type have potential impact on survival.


Subject(s)
Carcinoma, Neuroendocrine/pathology , Stomach Neoplasms/pathology , Adult , Aged , Carcinoma, Neuroendocrine/diagnosis , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/diagnosis
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 13(5): 371-4, 2010 May.
Article in Chinese | MEDLINE | ID: mdl-20499309

ABSTRACT

OBJECTIVE: To characterize oncogenic KIT signaling mechanisms in gastrointestinal stromal tumor(GIST), and to determine which signaling pathway might be of potential relevance to imatinib acquired resistance. METHODS: The mutations of KIT and PDGFRa gene were evaluated and KIT downstream signaling profiles were evaluated in 8 specimen from 5 GIST patients who were evaluated treated between 2003 and 2008 in our hospital. Biochemical inhibition of the expression of related proteins in Ras/Raf/MAPK and PI3-K/AKT pathways, such as KIT, mitogen-activated protein kinase(MAPK),mammalian target of rapamycin(MTOR), AKT, Proliferating cell nuclear antigen (PCNA) and BCL-2, were determined by Western blotting for protein activation. RESULTS: Three cases who showed response to imatinib carried primary mutations in KIT gene, with 2 cases possessing mutation in exon 11, 1 case in exon 13. One case with imatinib-resistance developed KIT secondary mutation, but all the cases had no PDGFRa mutation. p-KIT and p-AKT expressions were higher in the samples of imatinib-resistant GIST than those of imatinib-responsive GIST. Total KIT, MAPK, p-MAPK, p-MTOR expressions were strong and comparable in all varied GISTs, which had no significant difference between imatinib-resistant and imatinib-responsive samples. PCNA and BCL-2 expression varied in samples of different therapy cycles and different location. CONCLUSIONS: Ras/Raf/MAPK and PI3-K/AKT/MTOR pathways are essential to GIST pathogenesis. The KIT secondary mutation and PI3-K/AKT/MTOR pathway are particularly relevant for therapeutic targeting in imatinib-resistant GIST.


Subject(s)
Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/metabolism , Piperazines/pharmacology , Pyrimidines/pharmacology , Signal Transduction/drug effects , Benzamides , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Gastrointestinal Stromal Tumors/drug therapy , Humans , Imatinib Mesylate , Mutation , Proto-Oncogene Proteins c-kit/genetics , Signal Transduction/genetics
17.
Zhonghua Wei Chang Wai Ke Za Zhi ; 13(4): 270-2, 2010 Apr.
Article in Chinese | MEDLINE | ID: mdl-20422482

ABSTRACT

OBJECTIVE: To investigate the value of preoperative barium contrast examination for the diagnosis and operative planning in gastric cancer. METHODS: Clinical data of 229 gastric cancer patients were analyzed retrospectively. Lesions were divided into three parts: the cardiac, the body, and the antrum. The diagnostic accuracy of localization and the extent of tumor between gastroscopy alone and gastroscopy plus barium contrast were compared with the results of surgical findings. RESULTS: The diagnostic accuracy of localization and the extent of tumor for gastroscopy in the cardiac, the body and the antrum cancers were 100% and 78.4%, 94.6% and 86.5%, 98.1% and 84.6%, respectively, while for gastroscopy plus barium contrast were 100% and 84.8%, 100% and 91.9%, 99.0% and 90.4%, respectively. The diagnostic accuracy of both the localization and the extent of tumor were not significantly different between gastroscopy alone and gastroscopy plus barium contrast (P>0.05). Diagnostic accuracy of the length of esophagus infiltrated by cardiac cancer in gastroscopy was 60.6%, while in gastroscopy plus barium contrast was 90.9%, which was significantly different (P<0.05). Gastroscopy plus barium contrast was more accurate in predicting the possibility of thoracotomy in cardiac cancer infiltrating the lower esophagus. CONCLUSIONS: It is necessary to perform preoperative barium contrast examination in cardiac cancer patients, so as to identify whether the lower esophagus is infiltrated and to measure the length of lesion, which can provide evidences for making a decision of thoracotomy. For gastric body and antrum cancer, there is no indication for barium contrast examination if gastroscopy findings are satisfied.


Subject(s)
Adenocarcinoma/diagnostic imaging , Barium , Stomach Neoplasms/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Contrast Media , Female , Humans , Male , Middle Aged , Radiography , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 13(2): 125-8, 2010 Feb.
Article in Chinese | MEDLINE | ID: mdl-20186623

ABSTRACT

OBJECTIVE: To study the incidence, clinicopathological characteristics, diagnosis, treatment, and prognosis of synchronous or metachronous primary cancers in patients with gastric cancer. METHODS: Clinical data of 4426 patients with gastric cancer in our hospital from 1996 to 2007 were reviewed. RESULTS: Seventy-four (1.7%) patients had synchronous or metachronous primary cancer of other organ, of whom 10 were synchronous and 64 were metachronous. Colorectal cancer was the most common type of primary cancer in other organs (43.8%), followed by breast cancer (16.3%). The mean time interval between gastric cancer and metachronous primary cancer was 82.2 (3-354) months. The mean age at the diagnosis of gastric cancer was 61.2 (33-84) years. The 5-year overall survival rate was 42.3%. The 5-year survival rates in patients with synchronous cancer, pre-metachronous cancer or post-metachronous cancer were 15.2%, 42.9% and 51.3%, respectively. Causes of death were primary cancers of other organ in 11 patients, gastric cancer in 24, and renal failure in 1 patient. CONCLUSIONS: Primary cancer of other organ should be considered in the management of gastric cancer. Aggressive treatment should be used for the second primary cancer. Gastric cancer is the main cause of death in these patients.


Subject(s)
Breast Neoplasms , Colorectal Neoplasms , Neoplasms, Multiple Primary , Stomach Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasms, Multiple Primary/diagnosis , Prognosis , Stomach Neoplasms/diagnosis
19.
J Cancer Res Clin Oncol ; 136(7): 1065-71, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20043176

ABSTRACT

AIMS AND BACKGROUND: Most gastrointestinal stromal tumor (GIST) patients respond to KIT inhibition therapy of imatinib, but eventually become resistant with a median time to progression of 2 years. The mechanism of acquired resistance to imatinib and oncogenic KIT signal transduction in GISTs has not been well defined. We sought to investigate the spectrum of molecular and genomic changes in imatinib-resistant GIST patients. METHODS: KIT and PDGFRA mutations were evaluated in 48 samples obtained from 32 GIST patients who underwent surgery after imatinib treatment. KIT downstream signaling profiles were also investigated in eight specimens of five patients who were clinically responsive or resistant to imatinib therapy. Biochemical inhibition of KIT, mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (MTOR), AKT, proliferating cell nuclear antigen (PCNA) and BCL-2 were determined by western blotting for protein activation. RESULTS: In all 32 GIST patients, activating mutations in the KIT gene were seen in 26 (81.3%) patients, PDGFRA gene mutations were seen in 2 (6.2%) patients and no primary mutations were found in 4 (12.5%) patients. Secondary KIT mutations were identified in 11/14 (78.6%) imatinib-acquired-resistance patients, with nine patients in KIT gene exon17, and the other two in exon 13. The expressions of p-KIT, p-AKT, PCNA and BCL-2 were higher in the samples of imatinib-resistant GISTs than those of imatinib-responsive ones. P-KIT, p-AKT expressions were higher in imatinib acquired-resistance GISTs with secondary KIT mutations than imatinib-responsive ones with primary mutation. Total KIT, MAPK, p-MAPK, p-MTOR expressions were comparable in all varied GISTs. CONCLUSIONS: Novel additional mutations of KIT gene exon 13 or exon 17 indicate the likely mechanism of secondary resistance to imatinib. The PI3-K/AKT pathway might be more relevant than MEK/MAPK for therapeutic targeting in imatinib-resistant GIST patients with secondary mutation.


Subject(s)
Drug Resistance, Neoplasm , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/therapy , Piperazines/therapeutic use , Proto-Oncogene Proteins c-kit/genetics , Pyrimidines/therapeutic use , Receptors, Platelet-Derived Growth Factor/genetics , Adult , Aged , Benzamides , Disease Progression , Female , Follow-Up Studies , Gastrointestinal Stromal Tumors/diagnosis , Genotype , Humans , Imatinib Mesylate , Male , Middle Aged , Mutation , Proto-Oncogene Proteins c-kit/antagonists & inhibitors , Receptors, Platelet-Derived Growth Factor/antagonists & inhibitors , Signal Transduction/genetics
20.
World J Gastroenterol ; 16(1): 104-11, 2010 Jan 07.
Article in English | MEDLINE | ID: mdl-20039456

ABSTRACT

AIM: To examine whether acupuncture can prevent prolonged postoperative ileus (PPOI) after intraperitoneal surgery for colon cancer. METHODS: Ninety patients were recruited from the Fudan University Cancer Hospital, Shanghai, China. After surgery, patients were randomized to receive acupuncture (once daily, starting on postoperative day 1, for up to six consecutive days) or usual care. PPOI was defined as an inability to pass flatus or have a bowel movement by 96 h after surgery. The main outcomes were time to first flatus, time to first bowel movement, and electrogastroenterography. Secondary outcomes were quality of life (QOL) measures, including pain, nausea, insomnia, abdominal distension/fullness, and sense of well-being. RESULTS: No significant differences in PPOI on day 4 (P = 0.71) or QOL measures were found between the groups. There were also no group differences when the data were analyzed by examining those whose PPOI had resolved by day 5 (P = 0.69) or day 6 (P = 0.88). No adverse events related to acupuncture were reported. CONCLUSION: Acupuncture did not prevent PPOI and was not useful for treating PPOI once it had developed in this population.


Subject(s)
Colectomy/adverse effects , Colonic Neoplasms/surgery , Electroacupuncture , Ileus/prevention & control , Adult , Aged , Defecation , Female , Gastrointestinal Motility , Humans , Ileus/etiology , Ileus/physiopathology , Male , Middle Aged , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Postoperative Nausea and Vomiting/etiology , Postoperative Nausea and Vomiting/prevention & control , Prospective Studies , Quality of Life , Recovery of Function , Sleep Initiation and Maintenance Disorders/etiology , Sleep Initiation and Maintenance Disorders/prevention & control , Time Factors , Treatment Failure
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