Identification of Heterophilic Epitopes of H1N1 Influenza Virus Hemagglutinin.

Our previous studies found that the H1-50 monoclonal antibody (mAb) of influenza A virus hemagglutinin (HA) cross-reacted with pancreatic tissue and islet ß-cells, and further studies showed that H1-50 mAb binds to prohibitin (PHB) protein of islet ß-cells. These suggest that there are heterophilic epitopes between influenza virus HA and pancreatic tissue, which may be involved in the pathogenesis of type 1 diabetes. To further investigate these heterophilic epitopes, we screened binding epitopes of H1-50 mAb using a phage 12-peptide library. DNA sequencing and comparative analysis were performed on specific positive phage clones, and the sequence of 12-peptide binding to H1-50 mAb was obtained. The binding epitopes of H1-50 mAb in influenza virus HA were determined by sequence analysis and experimental verification, and their distribution within the three-dimensional structure was assessed by PyMOL. The results showed that H1-50 mAb specifically binds to polypeptides (306-SLPFQNIHPITIGK-319) of influenza A virus HA, located in the stem of the HA protein. However, there is no specific binding sequence between H1-50 mAb and the PHB protein of islet ß-cells in the primary structure, and we speculate that the binding of H1-50 mAb to islet ß-cells may depend on the spatial conformation. The identification of the heterophilic epitopes of H1N1 influenza virus hemagglutinin provides a new perspective on type 1 diabetes that may be caused by influenza virus infection, which may contribute to the prevention and control of influenza.

Machine learning-based gray-level co-occurrence matrix signature for predicting lymph node metastasis in undifferentiated-type early gastric cancer.

BACKGROUND: The most important consideration in determining treatment strategies for undifferentiated early gastric cancer (UEGC) is the risk of lymph node metastasis (LNM). Therefore, identifying a potential biomarker that predicts LNM is quite useful in determining treatment. AIM: To develop a machine learning (ML)-based integral procedure to construct the LNM gray-level co-occurrence matrix (GLCM) prediction model. METHODS: We retrospectively selected 526 cases of UEGC confirmed through pathological examination after radical gastrectomy without endoscopic treatment in four tertiary hospitals between January 2015 to December 2021. We extracted GLCM-based features from grayscale images and applied ML to the classification of candidate predictive variables. The robustness and clinical utility of each model were evaluated based on the following factors: Receiver operating characteristic curve (ROC), decision curve analysis, and clinical impact curve. RESULTS: GLCM-based feature extraction significantly correlated with LNM. The top 7 GLCM-based factors included inertia value 0° (IV_0), inertia value 45° (IV_45), inverse gap 0° (IG_0), inverse gap 45° (IG_45), inverse gap full angle (IG_all), Haralick 30° (Haralick_30), Haralick full angle (Haralick_all), and Entropy. The areas under the ROC curve (AUCs) of the random forest classifier (RFC) model, support vector machine, eXtreme gradient boosting, artificial neural network, and decision tree ranged from 0.805 [95% confidence interval (CI): 0.258-1.352] to 0.925 (95%CI: 0.378-1.472) in the training set and from 0.794 (95%CI: 0.237-1.351) to 0.912 (95%CI: 0.355-1.469) in the testing set, respectively. The RFC (training set: AUC: 0.925, 95%CI: 0.378-1.472; testing set: AUC: 0.912, 95%CI: 0.355-1.469) model that incorporates Entropy, Haralick_all, Haralick_30, IG_all, IG_45, IG_0, and IV_45 had the highest predictive accuracy. CONCLUSION: The evaluation results indicate that the method of selecting radiological and textural features becomes more effective in the LNM discrimination against UEGC patients. Additionally, the ML-based prediction model developed using the RFC can be used to derive treatment options and identify LNM, which can hence improve clinical outcomes.

Translation and validation of the Chinese version of the MD Anderson symptom inventory for measuring perioperative symptom burden in patients with gynecologic cancer.

BACKGROUND: Gynecologic cancers are among the most prevalent malignancies in China. Cervical and uterine cancer respectively account for the sixth and eighth highest incidence of cancer among Chinese women. Abdominal surgery is one of the important treatment methods for gynecological tumors. However, the tumor- and surgery-related symptom burden are not well studied owing to a lack of a standardized and validated assessment tool in the Chinese population. The study aimed to translate and validate the MD Anderson Symptom Inventory for measuring perioperative symptom burden in gynecologic cancer patients (MDASI-PeriOp-GYN) and examine the utility of the Chinese version of MDASI-PeriOp-GYN. METHODS: The MDASI-PeriOp-GYN was translated in a stepwise manner. First, two native speakers independently translated the 9 PeriOp-GYN symptom items. Then the nine items were translated back into English by two different bilingual translators. After discussion and revision, the four translators reached an agreement. Finally, the finalized Chinese version was administered to women with three common gynecologic cancer types (cervical, ovarian, and endometrial cancers) recruited from the gynecological oncology department of Sichuan Cancer Hospital & Institute between July and October 2019. The reliability and validity of the translated version were assessed. RESULTS: Overall, 324 women with gynecologic cancers were enrolled. Cronbach's α values were 0.826 and 0.735 for the symptom severity and interference scales, respectively. Test-retest reliability values were 0.885, 0.873, and 0.914 for symptom severity, PeriOp-GYN, and interference scales. Significant correlations were found between the MDASI-PeriOp-GYN-C and EORTC QLQ-C30 along with the QLQ-OV28 module (- 0.608-0.871, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by time intervals, surgery type, and functional status (all P < 0.01). CONCLUSIONS: The MDASI-PeriOp-GYN-C is a valid and reliable tool for measuring symptoms in Chinese patients undergoing surgery for gynecologic cancers. The tool could be used in clinical practice and clinical trials to instantly gather patients' health and quality of life data.

[Relationship between Aneurysm Volumetric Changes and Endoleaks after Endovascular Abdominal Aortic Aneurysm Repair].

Objective To evaluate the relationship of volumetric changes and endoleaks after endovascular aneurysm repair(EVAR)for abdominal aortic aneurysms(AAAs). Methods We retrospectively evaluated the clinical and imaging data of 54 patients who had underwent EVAR within 1 month after their aneurysms were detected.All patients received abdominal and pelvic enhanced computed tomography(CTA)for two follow-up visits in Peking Union Medical College Hospital from July 2014 to February 2019.Three-dimensional volumes and maximum diameters on axial CT of the aortic aneurysms were calculated by dedicated semi-automated 3D segmentation software before surgery(V0 and D0),in the 4 th postoperative month(V1and D1),and in the 12 th postoperative month(V2and D2),respectively.The presence or absence of endoleak for each patient with the V1/V0,V2/V0,and V2/V1 were calculated to assess the significance of volume changes with respect to endoleaks and the correlation between volume changes and maximum diameter changes on axial CT images. Results Of the 54 patients,endoleaks were found in 11 patients at the first follow-up visit(4 months after surgery),among whom 8 patients were arranged a second follow-up visit(12 months after surgery),during which endoleaks were found in 5 patients.Fifteen of 43 non-leaked patients underwent a second CTA examination,which revealed endoleak in one case.Patients who did exhibit endoleaks[n =11,V1/V0=1.086(1.033,1.116)]showed significant increases in aneurysm volume when compared with those who did not exhbit endoleaks[n =43,V1/V0=1.019(0.970,1.065)]at the first follow-up visit(Z=-2.695,P=0.007),although no significant difference was found with regard to volume changes between endoleaks(n=6,V2/V0=1.1±0.2,V2/V1=1.0±0.1)and non-endoleaks(n=17,V2/V0=1.0±0.1,V2/V1=1.0±0.1)at the second follow-up visit(t=0.725,P=0.476)as well as between these two follow-up visits(t=-0.021,P=0.984).V0 and D0 were moderately correlated with V1 and D1,respectively(r=0.5,P<0.001)and strongly correlated with V2 and D2,respectively(r=0.8,P<0.001).V1 and D1 were strongly correlated with V2 and D2,respectively(r=0.8,P<0.001). Conclusions The changes of aneurysm volume cannot reliably reflect the occurrence of endoleaks.The change of maximum axial diameter of aneurysm has certain correlation with the changes of aneurysm volume.

International consensus on natural orifice specimen extraction surgery (NOSES) for gastric cancer (2019).

At present, natural orifice specimen extraction surgery (NOSES) has attracted more and more attention worldwide, because of its great advantages including minimal cutaneous trauma and post-operative pain, fast post-operative recovery, short hospital stay, and positive psychological impact. However, NOSES for the treatment of gastric cancer (GC) is still in its infancy, and there is great potential to improve its theoretical system and clinical practice. Especially, several key points including oncological outcomes, bacteriological concerns, indication selection, and standardized surgical procedures are raised with this innovative technique. Therefore, it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES, which is of great significance for healthy and orderly development of NOSES worldwide.

CT Texture Analysis: A Potential Biomarker for Evaluating KRAS Mutational Status in Colorectal Cancer.

Objective Texture analysis is deemed to reflect intratumor heterogeneity invisible to the naked eyes. The aim of this study was to evaluate the feasibility of assessing the KRAS mutational status in colorectal cancer (CRC) patients using CT texture analysis. Methods This retrospective study included 92 patients who had histopathologically confirmed CRC and underwent preoperative contrast-enhanced CT examinations. The patients were assigned into a training cohort (n=51) and a validation cohort (n=41). We placed the region of interest in the tumour regions on the selected axial images using software of TexRad to extract a series of quantitative parameters based on the spatial scaling factors (SSFs), including mean, standard deviation (SD), entropy, mean of positive pixels (MPP), skewness, and kurtosis. The texture parameters and clinical characteristics (age, gender, tumour location, histopathology, tumour size, T, N, M stages) were compared between the mutated and wild-type KRAS patient groups in training cohort and validation cohort. Before building the multiple feature classifier, we calculated the correlations of the features using Pearson's correlation coefficient, and if any two features were significantly correlated, the one with lower AUC was removed. Ultimately, only the most discriminative isolated features were combined to train a supporting vector machine (SVM) classifier. The receiver operating characteristic (ROC) curve was processed for evaluating the diagnostic efficiency of texture parameters in differentiating CRC patients with mutated KRAS from those with wild-type KRAS. Results None of the clinical characteristics were significant different between CRC patients with wild-type KRAS and mutated KRAS in both cohorts. For predicting the expression of mutated KRAS in CRC patients, the perfect model which combined skewness on SSF 5 by unenhanced CT, entropy on SSF 2, skewness and kurtosis on SSF 0, and kurtosis and mean on SSF 3 by enhanced CT, showed a desirable AUC of 0.951 (95% CI: 0.895-1, P<0.001), with a sensitivity of 88.9% and a specificity of 91.7%, when the cut-off value was 0.46 in the training cohort; while in the validation cohort, the AUC value was 0.995 (95% CI: 0.982-1, P<0.001), the sensitivity was 100%, and the specificity was 93.7% when the cut-off value was 0.28. Conclusion It is feasible to evaluate the KRAS mutational status in CRC using CT texture analysis.

[Correlation between CT Texture Analysis and Synchronous Distant Metastasis in Patients with Lymph Node-negative Colorectal Cancer].

Objective To investigate the correlation between CT texture analysis and synchronous distant metastasis in patients with lymph node-negative colorectal cancer. Methods The preoperative CT images of 82 patients with lymph node-negative colorectal cancer were analyzed retrospectively.There were 12 patients with simultaneous distant metastasis and 70 patients without simultaneous distant metastasis.The maximum plane of the lesion on plain scan and portal CT images was analyzed by TexRAD software.When the spatial scaling factor(SSF)was 0 and 2-6,six texture parameters were obtained,and the differences of texture parameters between the two groups were compared.The counting data were analyzed by chi-square test and the measurement data by Mann-Whitney test. Results There was a significant difference in the skewness of SSF=3 between the simultaneous distant metastasis group and the non-synchronous metastasis group on plain CT scan(P=0.031).On contrast-enhanced CT images,the entropy values of SSF=2,3,5,and 6 were statistically significant(P=0.048,P=0.027,P=0.016,P=0.017),and the peak values of SSF=2 were statistically significant(P=0.026).According to the comprehensive analysis of the texture parameters of the six groups,when the boundary value was 0.636,the sensitivity and specificity for the diagnosis of simultaneous distant metastasis were 75% and 89%,respectively. Conclusion CT texture analysis is useful in the diagnosis of synchronous distant metastasis in patients with lymph node-negative colorectal cancer.

Application and Progress of Texture Analysis in the Therapeutic Effect Prediction and Prognosis of Neoadjuvant Chemoradiotherapy for Colorectal Cancer.

Colorectal cancer is one of the most common malignant tumors, and the morbidity and mortality are increasing gradually over the last years in China. Neoadjuvant chemoradiotherapy (nCRT) is currently applied to the treatment of colorectal cancer patients, and it is helpful to improve the prognosis. The sensitivity of patients to nCRT is different due to individual differences. Predicting the therapeutic effect of nCRT is of great importance for the further treatment methods. Texture analysis, as an image post-processing technique, has been more and more utilized in the field of oncologic imaging. This article reviews the application and progress of texture analysis in the therapeutic effect prediction and prognosis of nCRT for colorectal cancer.

[NSAIDs combined with radiotherapy to prevent heterotopic ossification after total hip arthroplasty].

OBJECTIVE: To investigate the preventive effects and differences of NSAIDs combined with radiotherapy, NSAIDs and radiotherapy for heterotopic ossification(HO) after total hip arthroplasty(THA). METHODS: From February 2015 to July 2016, 168 hips undergoing primary THA were divided into group A, B and C, and 163 patients were followed up (54 cases and 54 hips in group A, 55 cases and 55 hips in group B, 54 cases and 54 hips in group C). Among group A, 5 hips were primary osteoarthritis, 37 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 12 hips were secondary osteoarthritis due to acetabular dysplasia. Patients in group A received oral celecoxib (0.2 g, 2 times a day) for 2 weeks after operation. Among group B, 6 hips were primary osteoarthritis, 32 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 17 hips were secondary osteoarthritis due to acetabular dysplasia, all of which in group B were treated with preoperative single 7 Gy radiotherapy. Among group C, 5 hips were primary osteoarthritis, 35 hips were secondary osteoarthritis due to avascular necrosis of the femoral head, 14 hips were secondary osteoarthritis due to acetabular dysplasia. Patients in group C were treated with preoperative radiotherapy and celecoxib after operation. The side effects of gastrointestinal reactions were observed after operation, and the heterotopic ossification was evaluated by pelvic anterior and posterior X-ray (Brooker grading). RESULTS: The mean clinical and radiological follow-up was 21 months(12 to 30 months). In group A, 54 hips were followed up with 7 hips with heterotopic ossification, including 5 hips of Brooker I and 2 hips of Brooker II. In group B, 55 hips were successfully followed up, with 8 hips of heterotopic ossification occurred, including 6 hips of Brooker I, 2 hips of Brooker II. In group C, 54 hips were successfully followed up, with 5 hips of heterotopic ossification occurred , including 4 hips of Brooker I, 1 hip of Brooker II. There was no significant difference in efficacy among 3 groups (χ²=0.743, P=0.690) by chi-square test. The prevalence of side effects were as following: in group A, there were 6 hips with side effects;in group B, there were 6 hips with side effects;in group C, there were 7 hips with side effects. There was also no significant difference in side effects among 3 groups (χ²=0.135, P=0.935). CONCLUSIONS: The combined-therapy group has lower prevalence of HO than the NSAIDs group or radiotherapy group, but the statistical difference between them is not significant. NSAIDs is still the first choice to prevent HO after THA.

Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival.

OBJECTIVES: The long-term clinical characteristics, response to therapy, and survival in patients with immunoglobulin D (IgD) multiple myeloma (MM) were investigated. METHODS: A retrospective study was conducted that included 68 patients treated in the last 10 years, 37 of whom received bortezomib only (bortezomib group), 13 of whom received bortezomib and underwent autologous hematopoietic stem cell transplantation (bortezomib + ASCT group), and 18 of whom received conditional chemotherapy (non-bortezomib group). RESULTS: The ratio of males to females was 44:24, and the median age was 56.5 years. The overall response rate of each group was 91.9, 77.8, and 100%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 24 and 15.5 months, respectively, among the 68 patients. The median OS of each group was 23, 21.5, and 27 months, respectively. The median PFS of each group was 18, 12, and 24 months, respectively. The 3- and 5-year OS were 64 and 45%, respectively, and the 3- and 5-year PFS were 39 and 13%, respectively, among the 68 patients. Cox regression showed that the percentage of bone marrow plasmacytosis was significantly associated with OS (p = 0.038). CONCLUSIONS: The survival of IgD patients is shorter than that of other MM patients. Treatment strategies with bortezomib followed by stem cell transplantation may boost the response rate and improve survival.

RNAi-mediated downregulation of DNA binding protein A inhibits tumorigenesis in colorectal cancer.

DNA binding protein A (dbpA) belongs to the Y-box binding protein family and has been reported to play an important role in carcinogenesis. Our previous study demonstrated that the knockdown of dbpA in gastric cancer cells inhibited cell proliferation by modulating the cell cycle. However, the role of dbpA in human colorectal cancer (CRC) remains unclear. In this study, immunohistochemical (IHC) staining and clinicopathological parameter analysis were employed to detect dbpA expression in 44 paired CRC samples and 7 CRC cell lines. Lentivirus-mediated short hairpin RNA (shRNA) was used to silence dbpA, and the effects of dbpA knockdown on cell proliferation were determined by MTT assay, colony formation assay and flow cytometry. Furthermore, a xenograft model was established to observe tumor growth in vivo. Functional analysis indicated that dbpA was overexpressed in the CRC tissues and cell lines, and a high dbpA expression was associated with the depth of invasion (p<0.001), the degree of differentiation (p<0.001), lymphatic metastasis (p<0.001) and vessel invasion (p<0.001). The suppression of dbpA expression resulted in decreased cell proliferation in vitro and tumor growth in vivo, and it induced cell cycle arrest and promoted the apoptosis of the CRC cells. As a whole, our findings illustrate the crucial role of dbpA in colorectal tumorigenesis. Thus, dbpA may be used as a novel and potent therapeutic target in CRC.

Peripherally Inserted Central Catheter-Related Upper Extremity Venous Thrombosis in Oncology Patients: A Prospective Study Based on Doppler Sonography.

OBJECTIVES: Peripherally inserted central catheters (PICCs) are associated with an increased risk of venous thrombosis. This study had 2 objectives: to estimate the incidence of upper extremity venous thrombosis associated with PICCs in oncology patients and to evaluate the role of Doppler sonography in antithrombotic prophylaxis. METHODS: We conducted a prospective study with each patient being followed for 6 weeks. From April 2014 to October 2014, we analyzed a series of 245 consecutive oncology patients undergoing chemotherapy via PICCs, for an overall number of 246 PICC placements. We assessed the role of Doppler sonography for initiation of antithrombotic prophylaxis. The study group encompassed 2 cohorts of patients: those who received regular weekly Doppler screening for thrombosis prophylaxis and those who did not. RESULTS: Of 246 insertions, we observed 90 episodes of upper extremity venous thrombosis (36.59%); 62 of them were asymptomatic in the Doppler group, and 28 were symptomatic in the no-Doppler group. Patients in the Doppler group had a significantly lower rate of thrombosis (0%) than those in the no-Doppler group (23.53%; P < .01). CONCLUSIONS: Our prospective study suggests that the rate of PICC-related upper extremity venous thrombosis in oncology patients is high, and the occurrence of symptomatic thrombosis could be lowered with regular weekly Doppler screening after PICC insertions.

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma.

OBJECTIVES: To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma (CSCC). METHODS: Using retrospective analysis, 73 cases of CSCC were selected from Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, which were removed between January 2000 and January 2012. It was considered as experimental group. Meanwhile, 11 cases of normal skin specimens of non tumor patients were selected as control group. The expression level of c-fos and c-myc was compared in the two groups. RESULTS: The expressions of c-fos [72.60% (53/73)] and c-myc [83.56% (61/73)] in experimental group were statistically significant (P≤0.05) compared with control group (0%). Expression of c-myc protein was negatively related to differentiation of CSCC. The difference was statistically significant (χ(2)=7.26, P=0.001<0.05). While expression of c-fos protein was positively related to differentiation of CSCC, which was statistically significant (χ(2)=7.47, P=0.001 2<0.025). CONCLUSIONS: The expression level of c-fos and c-myc can be used as an important indicator of CSCC differentiation, and it has closely connection with the differentiated degree, which can guide clinical prognosis.

[Influence of siRNA interfering ß-catenin on tumorigenicity in vivo of K562 cell line].

The aim of this study was to investigate the effects of ß-catenin on the tumorigenicity of K562 cells in vivo. The ß-catenin expression in K562 cells was down-regulated through sequence-specific siRNA, and the treated K562 cells were implanted into BALB/c nude mouse subcutaneously. And the tumor-forming rate and tumor-forming curve (interference group) were observed. Experiments were divided into 3 group: interference group (implanted K562 cells transfected with ß-catenin interfering plasmid DNA), control group (implanted K562 cells transfected with unrelated sequence plasmid DNA) and untreated group (implanted K562 cells transfected without plasmid DNA). The results indicated that the tumor-forming rates of untreated group (n = 9), control group (n = 8) and interference group (n = 9) were 100%, 87.5% and 0% respectively. The tumor-forming rate of interference group was significantly lower than those of the other 2 groups (p < 0.001). Comparison of the tumor-forming curve between 3 groups, showed that in first 2 groups existed tumor-forming and their final tumor volumes were almost the same, but the tumor growth of untreated group was faster than that in control group; while in the interference group there was not tumor-forming. It is concluded that the ß-catenin expression level in K562 cells is down-regulated through the interference of sequence-specific siRNA, thus affecting their tumor-forming potential in vivo.

[Analysis of efficacy and related factors in 85 chronic myeloid leukemia patients treated with imatinib mesylate].

The objective of this study was to evaluate the efficacy of Imatinib on patients with chronic myeloid leukemia (CML) in chronic phase and to analyze its influencing factors. 85 patients received Imatinib mesylate at a dose of 300-600 mg orally per day, and were evaluated for hematologic, cytogenetic, and molecular responses. The results showed that the median follow-up was 21 (range 9 - 78) months. Cumulative complete hematological remission (CHR) rate was 100%, major cytogenetic remission (MCyR) rate was 80%, complete cytogenetic remission (CCyR) rate was 67.1% and complete molecular remission (CMoR) rate was 36.4%. The median time to complete hematological remission (CHR) was 1 (range 1 - 3) month, to complete cytogenetic remission (CCyR) was 6 (range 1 - 24) months. The estimated overall survival rates for patients who received Imatinib for 1, 2, 3 years were (98.7 +/- 1.3)%, (96.5 +/- 2.5)% and (90.1 +/- 6.6)% respectively. The estimated progression-free survival rates at 1, 2, 3 years were (97.6 +/- 1.6)%, (96.1 +/- 2.2)% and (90.0 +/- 1.4)% respectively. The CHR, MCyR and CCyR between low risk, intermediate risk and high risk groups according to the Sokal scoring system and between primarily treated and retreated groups all had no difference. The overall survival of patients who achieved MCyR or CCyR was better than that in patients only achieved hematologic remission (p = 0.026), but there was no significant difference in progression-free survival between them. Univariate analysis for efficacy of Imatinib mesylate revealed that WBC count < 100 x 10(9)/L (p = 0.024), Hb level > or = 130 g/L (p = 0.036), and peripheral basophil count < or = 0.05 (p = 0.024) before therapy were independent favourable factors for achieving MCyR or CCyR. It is concluded that the patients with CML in chronic phase treated with Imatinib can achieve the best hematologic remission and higher cytogenetic remission, it should be considered that the imatinib is a drug of the first-line therapy for untreated and treated patients with CML.

Upregulation of human DNA binding protein A (dbpA) in gastric cancer cells.

AIM: To determine the effect of human DNA binding protein (dbpA) on the biology of gastric cancer cells. METHODS: DbpA expression was analyzed by Western blot analysis and immunofluorescence staining in gastric cancer tissues and cell lines. A dbpA-specific small interference (si) RNA was designed and synthesized. Suppressive effect of siRNA on dbpA expression was assessed by real-time RT-PCR. Transwell migration and colony formation assays were used to assess the inhibitory effects of dbpA siRNA on cell invasion and tumorigenesis in vitro. Drug-sensitivity was evaluated using a conventional 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The expression of dbpA was upregulated in gastric cancer tissues and cell lines as compared to adjacent normal tissues or gastric epithelial cells. siRNA treatment successfully silenced dbpA expression. Silencing of dbpA increased expression of E-cadherin, decreased expression of adenomatous polyposis coli (APC), beta-catenin and cyclin D1, but had no effect on expression of NF-kappaB. Silencing of dbpA also suppressed cell invasion and colony formation of SGC7901 cells, and enhanced their chemosensitivity to 5-fluorouracil. CONCLUSION: DbpA plays an important role in the pathogenesis and development of gastric cancer, and the process involves E-cadherin, APC, beta-catenin and cyclin D1. Silencing of dbpA might be a novel therapeutic strategy for increasing chemosensitivity to 5-fluorouracil in gastric cancer.

[Analysis of relationship between bcr-abl transcription level detected by real-time quantitative polymerase chain reaction and clinical status of CML patients].

This study was aimed to investigate the bcr-abl transcription level and its relationship with the clinical status of patients so as to provide some bases for predicting patient status according to absolute value of bcr-abl transcript. The bcr-abl/abl values (%) of bone marrow samples from 30 newly diagnosed CML patients at the baseline bcr-abl/abl value obtained in CML patients with bcr-abl positive were defined, then 161 bone marrow samples from 82 patients were detected at virions time points, and the bcr-abl/abl value of each sample was compared with baseline value and its relationship with clinical status of patient at same time point was investigated. The results showed that bcr-abl/abl values (%) of 30 patients showed positive skew distribution and a large variation with mean 13.5631 (1.0206 - 98.3159) and mathematical mean of 21.1491 (95% CI: 12.3532 - 29.9450). For strict standard, the baseline value of bcr-abl/abl (%) was set as 1, the lower limit of these values. In the detected results of 161 samples, there were 33 samples' values above the baseline value, in which resistance/relapse/progression (R/R/P) 13 (39.4%, 13/33), no remission (NR) 17 (51.5%, 17/33) and complete hematologic remission (CHR) 3 (9.1%, 3/33) were observed. the values of 26 samples decreased by 0 - 1 order of magnitude (0.1 < or = bcr-abl/abl % < 1), in which R/R/P 6 (23.1%, 6/26), NR 7 (26.9%, 7/26), CHR 7 (26.9%, 7/26) and cytogenetic remission (CyR) 6 (23.1%, 6/26) were observed, the values of 19 samples decreased by 1 - 2 order of magnitude (0.01 < or = bcr-abl/abl % < 0.1), in which NR 2 (10.5%, 2/19), CHR 3 (15.8%, 3/19) and CyR 14 (73.7%, 14/19) were determined. 7 samples decreased by 2 - 3 order of magnitude (0.001 < or = bcr-abl/abl % < 0.01) in which major CyR (MCyR) 2 (28.6%, 2/7) and complete CyR (CCyR) 5 (71.4%, 5/7) were determined, the values of 76 samples decreased by 3 or more order of magnitude (bcr-abl/abl % < 0.001), and all these were CCyR. In conclusion, the using decrease degree of one time point-detected value compared to the baseline could well assess the patient clinical status. The bcr-abl/abl % < 0.01 can reliably reflect CyR obtained by patients at the time point, and bcr-abl/abl % < 0.001 can reflect CCyR obtained by patients. However, exact judgments of patient status relies on dynamic and serial monitoring.

[Expression of heparin-binding epidermal growth factor-like growth factor in patients with gastric carcinoma].

OBJECTIVE: To investigate the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in patients with gastric carcinoma in different stages. METHODS: The expressions of HB-EGF protein and mRNA in normal gastric tissues, metaplasic intestinal mucosa, early-stage gastric cancer and advanced-stage gastric cancer tissues were detected by immunohistochemistry and in situ hybridization. RESULTS: HB-EGF expression was only detected in the parietal cells of the gastric fundic glands and in gastrin cells of the pyloric glands in normal gastric tissues. Weak HB-EGF expression was detected in the epithelial cells of the gastric mucosa in intestinal metaplasic mucosa, and the expression increased in all layers of the gastric mucosa in early-stage gastric cancer. Intense HB-EGF expression was observed in advanced gastric cancer. CONCLUSION: Increased HB-EGF expression may be implicated in the pathogenesis and development of gastric carcinoma.

Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion.

AIM: To investigate the relation of expression transformation of claudin-1 with invasiveness and metastasis of gastric carcinoma. METHODS: By using immunohistochemistry, expression of claudin-1 in mucosa and invasive front of 136 gastric adenocarcinoma cases and proliferative index (Ki-67) were detected and analyzed. RESULTS: In mucosa, the claudin-1 over-expression rate of mucinous adenocarcinomas (including signet-ring cell carcinomas) was the highest. It was negatively related with the differentiation but positively related with the invasiveness and metastasis of gastric cancer. In invasive front, the claudin-1 over-expression rate was positively related with the differentiation, invasiveness and metastasis of gastric carcinoma. The expression transformation of claudin-1 was found in gastric carcinoma. The expression of claudin-1 in invasive front was transformed in 28/136 gastric carcinoma cases. The transformation rate in highly differentiated tubular adenocarcinomas was the highest (51.5%, 17/33). The deeper was the invasiveness, the higher was the transformation rate. The claudin-1 expression transformation rate in serosa and omenta was significantly higher (92.9%) than in tunica muscularis of invasive gastric cancer cases, as well as in patients with lymph node metastasis than in those without lymph node metastasis. CONCLUSION: Up-regulation of claudin-1 expression and its transformation in invasive and metastatic gastric carcinoma suggest that claudin-1 participates in the transformation of biological behaviors in neoplasms. Further study is needed to elucidate the precise mechanism and the relation of claudin-1 expression with the neoplasm progress.