Transplant-related Symptom Clusters in Renal Transplant Recipients.

Renal transplant recipients experience multiple symptoms, but complex relationships among these symptoms remain poorly understood. To explore the existence of symptom clusters in renal transplant recipients. A total of 295 renal transplant recipients were recruited in a hospital in Tianjin from October 2017 to January 2018. The participants completed the symptom questionnaire that assessed three symptom dimensions of 62 symptoms. Exploratory factor analysis was performed to identify symptom clusters. Five symptom clusters were extracted through exploratory factor analysis: emotional-sleep symptom cluster, pain-gastrointestinal symptom cluster, immune-related symptom cluster, lack of energy symptom cluster, and visual dysfunction symptom cluster, which explained 50.53% of the variance of symptom experience. Renal transplant recipients experienced a complex series of symptoms, and some symptoms related to one another formed a symptom cluster. Adopting a symptom cluster approach has the potential to remarkably enhance symptom assessment and nursing care for renal transplant recipients.

Integrative analysis of immune microenvironment-related CeRNA regulatory axis in gastric cancer.

This study aimed to identify significant immune microenvironment-related competing endogenous RNA (CeRNA) regulatory axis in gastric cancer (GC). Analysis of differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) was performed for the microarray datasets. After abundance analysis of immune cell's infiltration, immune-related mRNAs and lncRNAs were obtained. Meanwhile, according to the Pearson correlation coefficient between immune-related mRNAs and lncRNAs, the co-expression mRNA-lncRNA pairs were screened. Furthermore, the target genes of co-existance miRNAs were predicted, and miRNA-lncRNA pairs were identified. Finally, the lncRNA-miRNA and miRNA-mRNA relationship regulated by the same miRNA was screened. Combining with the co-expression relationship between lncRNA and mRNA, the CeRNA network was constructed. In abundance analysis of immune cell's infiltration, a total of eight immune cells were obtained, in addition, 83 immune-related DElncRNAs and 705 immune-related DEmRNAs were screened. KEGG pathway enrichment analysis showed that these mRNAs were mainly involved in PI3K-Akt signaling pathway and human papillomavirus infection, while lncRNA were relevant to gastric acid secretion. A total of 25 miRNAs were significantly associated with immune-related mRNAs, such as hsa-miR-148a-3p, hsa-miR-17-5p, and hsa-miR-25-3p. From the mRNA-miRNA-lncRNA CeRNA network, we observed that AC104389.28─miR-17-5─SMAD5 axis and LINC01133─miR-17-5p─PBLD axis played a crucial role in the development of GC. Furthermore, resting memory CD4 T cells and plasma cells were closely associated with the pathogenesis of GC, and these immune cells might be affected by the key genes. The present study identified key genes that associated with immune microenvironment in GC, providing potential molecular targets for immunotherapy of GC.

Development and Validation of a Simplified Chinese Version of the Assessment Tool for Students' Perceptions of Medical Professionalism.

Professionalism is crucial in all professions and is particularly important in the medical field. Measuring students' perceptions of professionalism can help to form education targeting the enhancement of professionalism. This study aimed to validate an effective assessment tool for the measurement of medical students' perceptions of medical professionalism in mainland China. The cross-sectional survey was conducted in three medical colleges in Guangdong, China. Of the 2103 eligible medical students, 1976 responded, and 1856 questionnaires were deemed valid. Students from clinical medicine in these three medical colleges were randomly selected by cluster sampling. First, a Simplified Chinese Version questionnaire to measure Student's Perception of Medical Professionalism (SCV-SPMP) was constructed. Second, questionnaires from 1856 students majoring in clinical medicine at three medical colleges were included in the analysis. Third, exploratory factor analysis, Cronbach's alpha, item-subscale correlation, and confirmatory factor analysis were conducted to test the validity and reliability of the SCV-SPMP. Nine items were eliminated following exploratory factor analysis, and four subscales were extracted from the analysis. All internal consistency reliability exceeded the minimum standard. The overall Cronbach's alpha was 0.94, and four subscales' alphas were 0.82 (Accountability and excellence), 0.81 (Duty), 0.89 (Honor and integrity), and 0.85 (Practice habits and respect for others), respectively. The model fit was good. The convergent validity and discriminant validity were acceptable. The modified SCV-SPMP was found to be a valid and reliable tool to capture the main features of Chinese students' perceptions of medical professionalism in four dimensions, and it provides a quantitative method for the measurement of the students' perceptions in mainland China..

[Choline improves lipopolysaccharide-induced central nervous system inflammatory response and cognitive dysfunction in mice].

OBJECTIVE: To assess the effect of choline in ameliorating lipopolysaccharide (LPS)-induced central nervous system inflammation and cognitive deficits in mice and explore the underlying mechanism. METHODS: Seventy-two mice were randomized into saline control group, LPS group, choline intervention group and choline control group. In the latter two groups, the mice received pretreatment with intraperitoneal injections of choline (40 mg/kg, 3 times daily for 3 consecutive days) prior to microinjection of LPS into the lateral cerebral ventricle to induce central nervous system inflammation; in saline and LPS groups, the mice were pretreated with saline in the same manner before intraventicular injection of artificial cerebrospinal fluid. Choline treatment was administered in the mice till the end of the experiment. The locomotor activity and spatial learning and memory capacity of the mice were examined. The expressions of Iba1 protein and proinflammatory cytokines (TNF-α and IL-ß) I the hippocampal dentate gyrus, and the expressions of α 7nAchR, p38 MAPK and phosphorylated p38 MAPK in the hippocampus of the mice were detected. RESULTS: Water maze test showed that compared with the saline control group, the mice in LPS group exhibited significantly reduced platform crossings (P<0.05), which was significantly increased by choline pretreatment (P<0.05). The mice pretreated with LPS expressed obviously increased levels of IBA-1 protein, TNF-α, and IL-1ß in the hippocampus (P<0.01), and choline pretreatment significantly lowered the expressions of IBA-1 protein and IL-1ß (P<0.05). The phosphorylation level of p38 MAPK increased significantly after LPS pretreatment (P<0.05), and was reduced by choline pretreatment (P<0.05); α 7nAchR expression increased significantly in choline intervention group as compared with that in the other 3 groups (P<0.05). CONCLUSION: Choline can probably antagonize LPS-induced hippocampal p38 MAPK phosphorylation in mice via the α 7nAchR signaling pathway to protective against LPS-induced neuroinflammation and cognitive impairment in mice.

[Synergistic analgesic effect of choline and parecoxib sodium in mice and the mechanism].

OBJECTIVE: To investigate the synergistic analgesic effect of choline and parecoxib sodium and study its mechanism. METHODS: In male Kunming mice with acetic acid-induced writhing, the ED50 of choline and parecoxib sodium (administered via the tail vein at 2 h and 30 min before modeling, respectively) and their combined use were determined. In saline (control) group, ED50 choline (C) group, ED50 parecoxib sodium (P) group, and 1/2ED50 choline and parecoxib sodium (1/2[C+P]) group, blood samples were collected from the eyeball 10 min after intraperitoneal administration of acetic acid to detect the levels of IL-1, TNF-α, PGE2, NF-κB, and I-κB levels using ELISA kits. RESULTS: In the acetic acid-induced writhing model, the ED50 of choline and parecoxib sodium was 8.64 and 6.33 mg/kg, and when combined, their ED50 was 2.13 and 1.56 mg/kg, respectively. The isobolograms of parecoxib sodium and choline showed that the measured ED50 of the two drugs combined was below the theoretical ED50 value (P<0.05) with a combination index (CI) of <0.9. Compared with the control group, C group, P group, and 1/2 (C+P) group all showed significantly lowered IL-1 and TNF-α levels (P<0.05), especially in 1/2 (C+P) group (P<0.05). PGE2 level was significantly lower in P group and 1/2 (C+P) group compared with the control group (P<0.05). NF-κB and I-κB levels were significantly lowered in C, P, and 1/2 (C+P) groups (P<0.05), and the reduction was the most obvious in 1/2 (C+P) group (P<0.05). CONCLUSION: Choline and parecoxib sodium has a synergistic analgesic effect, and their interactions may involve the in vivo expression of NF-κB.

[Protective effect of dexmedetomidine against glutamate-induced cytotoxicity in PC12 cells and its mechanism].

OBJECTIVE: To investigate the protective effects of dexmedetomidine (Dex) against glutamate-induced cytotoxicity in PC12 cells and its mechanism. METHODS: PC12 cells were treated with varying concentrations of dexmedetomidine 1 h before exposure to a high concentration of glutamate. The cell viability was measured by MTT assay, and LDH release, MDA content and SOD activity were measured. The level of ROS was tested by DCFH-DA staining and flow cytometry. The level of intracellular Ca2+ was detected by Fluo-8 staining and flow cytometry, and the mitochondrial membrane potential (MMP) was determined with JC-1 staining and flow cytometry. RESULTS: Within the concentration range of 0.01 to 100 µmol/L, Dex dose-dependently protected PC12 cells against glutamate-induced cytotoxicity. Treatment with 100 µmol/L Dex significantly increased the cell viability to (86.6∓2.2)% of that of the control cells (P<0.01) and decreased LDH release to 1.4∓0.1 folds of the control level (P<0.01). In PC12 cells exposed to glutamate, Dex pretreatment significantly reduced MDA content (P<0.01), enhanced SOD activity (P<0.01), inhibited ROS overproduction (P<0.01), reduced intracellular Ca2+ level (P<0.01) and maintained a stable MMP (P<0.01). CONCLUSION: Dexmedetomidine can protect PC12 cells against glutamate-induced injury possibly in relation with its anti-oxidative activity, inhibitory effect on intracellular calcium overload and protective effect of the mitochondria.

Is there a role of surgery in patients with recurrent or metastatic gastrointestinal stromal tumours responding to imatinib: a prospective randomised trial in China.

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.

Prognostic factors influencing event-free survival and treatments in desmoid-type fibromatosis: analysis from a large institution.

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.

Impact of lymphatic and/or blood vessel invasion in stage II gastric cancer.

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.

Fibroblast growth factor receptor 4 regulates proliferation and antiapoptosis during gastric cancer progression.

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.

Sox17 regulates proliferation and cell cycle during gastric cancer progression.

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.

Prognostic analysis of familial gastric cancer in Chinese population.

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.

[Oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor].

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.

[Fuzzy recognition research on explosive and illegal drug based on terahertz spectroscopy detection].

On the base of absorption spectra in the range from 0.2 to 2.6 THz of seven common dangerous goods using terahertz time-domain spectroscopy (THz-TDS) technique, the THz absorption spectra of seven dangerous goods were identified successfully by fuzzy recognition. Using different feature absorption peaks of explosive and illegal drugs such as RDX, gamma-HNIW, DNT, MA and Ketamine as data source of fuzzy cluster analysis, fuzzy similar matrix was built by correlation coefficient, fuzzy equivalent matrix was obtained by the method of transitive closure, standard model bank of THz absorption spectra was formed, and data were preprocessed by range analysis and compute Hamming approach degree. It was concluded that uninspected goods were RDX hidden behind the uniform and MDA. The research indicated that different feature absorption by interactions between molecules and phonon resonance mode is the basis for determining the type and category of dangerous goods, it is feasible to apply fuzzy recognition to the identification of dangerous goods, providing an effective new method for the secure inspection and identification of threats using THz-TDS technique.

Molecular mechanisms of secondary imatinib resistance in patients with gastrointestinal stromal tumors.

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.

Study on the different expression of molecular markers between cardiac cancer and distal gastric cancer and their correlations with clinicopathological features.

BACKGROUND AND AIM: Currently, few studies have reported the different expression of molecular markers between distal gastric cancer and cardiac cancer. Here, we sought to make an investigation about it by a retrospective analysis. METHODS: The expression of 8 proteins, including epidermal growth factor receptor, glutathione S-transferase pi (GST-pi), cyclin D1, Neu/Her-2, C-myc, p53, p27 and p21, were evaluated in 110 cases with cardiac cancer and 101 cases with distal gastric cancer who underwent curative surgery at the Cancer Hospital, Fudan University, in 2005 by immunohistochemistry method. RESULTS: The TNM stage, differentiation grade, invasion depth and lymph node metastasis were significantly different between cardiac cancer and distal gastric cancer. p21 (p = 0.034), Neu (p = 0.017), and GST-pi (p = 0.003) were expressed in relatively higher levels in cardiac cancer than in distal gastric cancer. Furthermore, the clinical pathological parameters were significantly correlated with the expression of molecules mentioned above. CONCLUSION: Different molecular mechanisms may be involved in the tumorigenesis and development of cardiac cancer and distal gastric cancer.

Prognostic factors for extra-abdominal and abdominal wall desmoids: a 20-year experience at a single institution.

BACKGROUND AND OBJECTIVE: Previous reports even large studies discussing the prognosis of desmoids have included tumors from intra- and extra-abdominal sites as well as incomplete resection. The purpose of this study was to explore prognostic factors associated with the recurrence free survival (RFS) rate in surgically treated extra-abdominal and abdominal wall desmoids. PATIENTS AND METHODS: A total of 198 consecutive desmoid patients were treated with surgery over a 20-year period at a single institution. Of these, 151 patients with extra-abdominal and abdominal wall tumors were retrospectively reviewed. One hundred thirteen patients were referred for the primary tumor and the other 38 for recurrent disease initially treated elsewhere. All patients underwent a macroscopically complete resection. RESULTS: The median follow-up interval was 102 months. Thirty-one patients (20.5%) had a local recurrence (LR). No patients died of the disease. The 5- and 10-year RFS was 79.7% and 78.5%, respectively. Admission status, gender, tumor size, margin status, location, and number, were predictors of LR in univariate analysis. Tumor size and margin status were independent prognostic factors in multivariate analysis. Positive margins were predictive of recurrence of primary disease, and also showed a trend for recurrent disease, which was not statistically significant. The selective use of adjuvant radiation did not show significant benefit over local control. CONCLUSIONS: Regardless of primary or recurrent disease, microscopically negative margins should always be the goal for extra-abdominal desmoids surgery, if no cosmetic defects or function demolition is encountered. Extra-abdominal desmoids deserve more attention and should be treated more aggressively, especially when leaving positive margins.

[Surgical treatment for patients with advanced gastrointestinal stromal tumor after targeted therapy].

OBJECTIVE: To explore the role of surgery and its long-term outcome in patients with advanced gastrointestinal stromal tumor(GIST) treated with imatinib preoperatively. METHODS: Thirteen patients receiving imatinib therapy preoperatively, were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection. RESULTS: Thirteen patients, including 3 patients with locally advanced primary GIST and 10 patients with recurrent or metastatic GIST, underwent surgery after preoperative treatment with imatinib. Complete resections were accomplished in 4 of the 5 responsive disease(RD) patients, and in 1 of the 8 progression disease(PD) patients (38.5%). The progression-free survival(PFS) time for patients with RD and PD were 24.8 months and 2.8 months respectively. The difference of PFS between patients with RD and those with PD was significant(P<0.01). Median overall survival(OS) was not reached in both patients with RD and PD. The difference of OS between patients with RD and those with PD was not significant(P>0.05). CONCLUSION: Surgical intervention following imatinib is feasible and can be considered for patients with advanced GIST responsive to imatinib.

[Status and clinical analysis of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors].

OBJECTIVE: To investigate the status of c-kit and PDGFRA mutations in the gastrointestinal stromal tumors (GIST) and explore the relationship between the mutations and the clinical features. METHODS: One hundred and forty-one cases were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9,11,13, 17 of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct sequencing. The relations of clinical features and mutational status were analyzed with statistical tools in this study. RESULTS: Among the 141 GISTs, c-kit mutations were identified in 76.6% (108/141): 70.2% (99/141) involving exon 11, 5.7% (8/141) involving exon 9, 0.7% (1/141) involving exon 13 and no mutation detected in exon 17. The gene mutations were mostly heterogeneous. The c-kit exon 11 mutational format included deletion (65.7%), point mutation (24.2%) and insert duplications(10.1%).The mutations clustered in the classic "hot spot" at the 5' end of the exon mostly heterogeneous and the second "hot spot" were internal tandem duplications (ITD) at the 3' end of the exon. PDGFRA mutations were totally identified in 12.1%(4/33) of no-c-kit-mutation GISTs and 40%(4/10) of CD117-negative GISTs: all involving exon 18 with the mutations D842V. With the analysis between clinical features and mutation status, the significant difference of gene mutation rate in the different primary tumor organs (chi(2)=7.229, P=0.027, chi(2)=7.000,P=0.03) and no significant differences between the groups of age,gender,tumor size,mitotic rate,grade of malignant potential were found. CONCLUSION: Most GISTs have the c-kit or PDGFRA gene mutation. There are significant difference between mutation and primary tumor organ.

The analysis of status and clinical implication of KIT and PDGFRA mutations in gastrointestinal stromal tumor (GIST).

BACKGROUND AND OBJECTIVE: To analyze the frequency and spectrum of KIT and platelet-derived growth factor receptor-alpha (PDGFRA) gene in a large series of study and to explore the clinical implication of mutations in the gastrointestinal stromal tumors (GISTs) in China. METHOD: A total of 141 GISTs were subject to mutation analysis of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) using PCR amplification and direct sequencing. Clinicopathologic characteristics were correlated to gene mutations. RESULTS: Of the 141 tumors studied, approximately 76.6% had KIT gene mutations, 2.8% had PDGFRA gene mutations and 20.6% had a wild-type gene of KIT and PDGFRA. Among those with KIT gene mutations, 70.2% occurred in exon 11, 5.7% in exon 9, 0.7% in exon 13, and no mutation was detected in exons 17. The most frequent sites of mutation were in exon 11 and the mutations clustered in the classic "hot spot" at the 5'end of the exon mostly heterogeneous and the second "hot spot" were internal tandem duplications (ITD) at the 3'end of the exon. The overall mutation rate was significantly lower in GISTs originated from colorectum or extra-gastrointestinal tract (chi(2) = 6.728, P = 0.009; chi(2) = 4.059, P = 0.044), however, mutation rate on exon 11 was significantly increased in gastric stromal tumor (chi(2) = 5.713, P = 0.017; chi(2) = 4.341, P = 0.037). There were no significant differences in terms of age, gender, tumor size, mitotic counts, grade of malignant potential and liver metastasis in patients with or without gene mutations. CONCLUSION: KIT and PDGFRA gene were frequently found in patients with GISTs. Gene mutation rate varies in originated organ.