Simulation of double resonant excitation of ions in an asymmetric linear ion trap mass analyzer.

RATIONALE: Improving the analytical performance of linear ion traps (LITs) is crucial for the advancement of high-performance LIT mass spectrometers. In this study, a double resonant excitation method was employed in an asymmetric LIT to achieve high ion unidirectional ejection efficiency and enhanced mass resolution. METHODS: The asymmetric trapping field was generated by stretching one x electrode with a distance α. The double resonant excitation was achieved by applying an alternating voltage out of phase and a supplementary alternating voltage in phase to the x and y electrode pairs of the LIT, respectively. Numerical simulations of ion trajectories were performed to validate the effectiveness of this method. RESULTS: The mass resolution of the asymmetric LIT with double resonant excitation could be improved to ~3800, which was over two times compared to that with only dipolar resonant excitation, while both reached ~90% in ion unidirectional ejection efficiency. CONCLUSIONS: By employing the double resonant excitation method, the mass resolution could be improved significantly in the asymmetric LIT, while maintaining a considerably high ion unidirectional ejection efficiency. This method might provide a general solution for enhancing ion detection efficiency and mass resolution of LIT mass spectrometers.

Differential diagnosis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma based on spatial and channel attention mechanisms.

BACKGROUND: The pre-operative non-invasive differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) mainly depends on imaging. However, the accuracy of conventional imaging and radiomics methods in differentiating between the two carcinomas is unsatisfactory. In this study, we aimed to establish a novel deep learning model based on computed tomography (CT) images to provide an effective and non-invasive pre-operative differential diagnosis method for HCC and ICC. MATERIALS AND METHODS: We retrospectively investigated the CT images of 395 HCC patients and 99 ICC patients who were diagnosed based on pathological analysis. To differentiate between HCC and ICC we developed a deep learning model called CSAM-Net based on channel and spatial attention mechanisms. We compared the proposed CSAM-Net with conventional radiomic models such as conventional logistic regression, least absolute shrinkage and selection operator regression, support vector machine, and random forest models. RESULTS: With respect to differentiating between HCC and ICC, the CSAM-Net model showed area under the receiver operating characteristic curve (AUC) values of 0.987 (accuracy = 0.939), 0.969 (accuracy = 0.914), and 0.959 (accuracy = 0.912) for the training, validation, and test sets, respectively, which were significantly higher than those of the conventional radiomics models (0.736-0.913 [accuracy = 0.735-0.912], 0.602-0.828 [accuracy = 0.647-0.818], and 0.638-0.845 [accuracy = 0.618-0.849], respectively. The decision curve analysis showed a high net benefit of the CSAM-Net model, which suggests potential efficacy in differentiating between HCC and ICC in the diagnosis of liver cancers. CONCLUSIONS: The proposed CSAM-Net model based on channel and spatial attention mechanisms provides an effective and non-invasive tool for the differential diagnosis of HCC and ICC on CT images, and has potential applications in diagnosis of liver cancers.

Adjuvant Radiotherapy After Minimally Invasive Surgery in Patients With Stage IA1-IIA1 Cervical Cancer.

To estimate whether adjuvant radiotherapy is necessary for patients with stage IA1-IIA1 cervical cancer after laparoscopic hysterectomy, 221 patients were retrospectively analyzed. Sixty-two of them were treated with laparoscopic hysterectomy and adjuvant radiotherapy (group A), 115 underwent open surgery (group B) and 44 received laparoscopic hysterectomy alone (group C). Results showed that the 3-year local recurrence-free survival (LRFS) rates of group A, B and C were 98.4%, 97.4% and 86.4%, respectively. The LRFS rates of group A and B surpassed C (A vs. B, p=0.634; A vs. C, p=0.011; B vs. C, p=0.006). The inter-group differences of 3-year overall survival (OS) and distant metastasis free survival (DMFS) were not statistically significant. In subgroup analysis of stage IB disease, the 3-year LRFS rates of group A, B and C were 100%, 98.8% and 83.1%, the 3-year OS rates of group A, B and C were 100%, 98.9% and 91.5%, respectively. The 3-year LRFS and OS rates of group A and B were significantly superior to group C (p<0.05). Our findings suggest that adjuvant radiotherapy can reduce the risk of recurrence for women with early-stage cervical cancer after laparoscopic hysterectomy and bring survival benefits for patients with stage IB disease.

Baicalin attenuates adriamycin-induced nephrotic syndrome by regulating fibrosis procession and inflammatory reaction.

BACKGROUND: Baicalin has anti-inflammatory, antibacterial, blood platelet aggregation-inhibiting, free oxygen radical-clearing, and endotoxin-decreasing properties. However, its molecular mechanism involved in the treatment of Adriamycin-induced nephrotic syndrome (NS) is still unclear. OBJECTIVE: This study aimed to explore the effects of baicalin on Adriamycin-induced nephrotic syndrome (NS) and to characterize the genes involved in this progression. METHODS: We established Adriamycin-induced NS model in 32 rats and used six rats in Sham group. Urinary total protein content and creatinine serum were assessed as physiological indicators. H&E staining was used to observe the pathological changes. We determined gene expression profiles using transcriptome sequencing in the rat kidney tissues from Sham, Adriamycin, and Adriamycin + baicalin groups. KEGG was carried out to analyze the enriched pathways of differentially expressed genes among these groups. RESULTS: Baicalin treatment relieved renal injury in NS rats. Expression of 363 genes was significantly different between the Adriamycin and Adriamycin + baicalin M groups. Most of the differentially expressed genes were enriched in pathways involved in epithelial-mesenchymal transition (EMT), fibrosis, apoptosis, and inflammation. CONCLUSIONS: Overall, these data suggest that Adriamycin-induced NS can be attenuated by baicalin through the suppression of fibrosis-related genes and inflammatory reactions. Baicalin is a potential drug candidate for the treatment of NS, and the identified genes represent potential therapeutic targets.

Half-Brain Delineation for Prediction of Radiation-Induced Temporal Lobe Injury in Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

PURPOSE: To investigate the role of half-brain delineation in the prediction of radiation-induced temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 220 NPC cases treated with IMRT and concurrent platinum-based chemotherapy were retrospectively analyzed. Dosimetric parameters of temporal lobes, half-brains, and brains included maximum dose (Dmax), doses covering certain volume (DV) from 0.03 to 20 cc and absolute volumes receiving specific dose (VD) from 40 to 80 Gy. Inter-structure variability was assessed by coefficients of variation (CV) and paired samples t-tests. Receiver operating characteristic curve (ROC) and Youden index were used for screening dosimetric parameters to predict TLI. Dose/volume response curve was calculated using the logistic dose/volume response model. RESULTS: CVs of brains, left/right half-brains, and left/right temporal lobes were 9.72%, 9.96%, 9.77%, 27.85%, and 28.34%, respectively. Each DV in temporal lobe was significantly smaller than that in half-brain (P < 0.001), and the reduction ranged from 3.10% to 45.98%. The area under the curve (AUC) of DV and VD showed an "increase-maximum-decline" behavior with a peak as the volume or dose increased. The maximal AUCs of DVs in brain, half-brain and temporal lobe were 0.808 (D2cc), 0.828 (D1.2cc) and 0.806 (D0.6cc), respectively, and the maximal AUCs of VDs were 0.818 (D75Gy), 0.834 (V72Gy) and 0.814 (V70Gy), respectively. The cutoffs of V70Gy (0.86 cc), V71Gy (0.72 cc), V72Gy (0.60 cc), and V73Gy (0.45 cc) in half-brain had better Youden index. TD5/5 and TD50/5 of D1.2cc were 58.7 and 80.0 Gy, respectively. The probability of TLI was higher than >13% when V72Gy>0 cc, and equal to 50% when V72Gy = 7.66 cc. CONCLUSION: Half-brain delineation is a convenient and stable method which could reduce contouring variation and could be used in NPC patients. D1.2cc and V72Gy of half-brain are feasible for TLI prediction model. The dose below 70 Gy may be relatively safe for half-brain. The cutoff points of V70-73Gy could be considered when the high dose is inevitable.

[Establishment of Quantitative SPR Assay for Antibodies Against Human Platelet Antigen-1a].

OBJECTIVE: To establish quantitative surface plasmon resonance (SPR) assay for antibodies against human platelet antigen-1a (HPA-1a). METHODS: Recombinant protein was fixed on the chip surface by amino coupling method. SPR assay was used to detect the standard antibodies against HPA-1a at different conceatration. The optimal experimental parameters were determined, and standard curves were constructed with linear regression. Moreover, the sensitivity, specificity, accuracy and precision of the assay were evaluated. RESULTS: The quantitative SPR assay for HPA-1a antibodies was established. The determination ranges were 0-20 IU, with accuracy (recovery rate) was 97.75%-103.08%. The intra-assay precision [coefficients of variation (CV)] was 3.53%-4.29%, and the inter-assay precision (CV) was 2.08%-4.40%. For specificity test, several kinds of monoclonal and human antibodies against platelet membrane protein were tested and no positive result was observed. CONCLUSION: The established quantitative SPR assay for HPA-1a antibodies shows good sensitivity, specificity, accuracy and precision, and this rapid and simple method provides a new reference method for scientific research and clinical antibody detection.

Potential Defects and Improvements of Equivalent Uniform Dose Prediction Model Based on the Analysis of Radiation-Induced Brain Injury.

PURPOSE: To study the impact of dose distribution on volume-effect parameter and predictive ability of equivalent uniform dose (EUD) model, and to explore the improvements. METHODS AND MATERIALS: The brains of 103 nasopharyngeal carcinoma patients treated with IMRT were segmented according to dose distribution (brain and left/right half-brain for similar distributions but different sizes; V D with different D for different distributions). Predictive ability of EUDV D (EUD of V D ) for radiation-induced brain injury was assessed by receiver operating characteristics curve (ROC) and area under the curve (AUC). The optimal volume-effect parameter a of EUD was selected when AUC was maximal (mAUC). Correlations between mAUC, a and D were analyzed by Pearson correlation analysis. Both mAUC and a in brain and half-brain were compared by using paired samples t-tests. The optimal D V and V D points were selected for a simple comparison. RESULTS: The mAUC of brain/half-brain EUD was 0.819/0.821 and the optimal a value was 21.5/22. When D increased, mAUC of EUDV D increased, while a decreased. The mAUC reached the maximum value when D was 50-55 Gy, and a was always 1 when D ≥55 Gy. The difference of mAUC/a between brain and half-brain was not significant. If a was in range of 1 to 22, AUC of brain/half-brain EUDV55 Gy (0.857-0.830/0.845-0.830) was always larger than that of brain/half-brain EUD (0.681-0.819/0.691-0.821). The AUCs of optimal dose/volume points were 0.801 (brain D2.5 cc), 0.823 (brain V70 Gy), 0.818 (half-brain D1 cc), and 0.827 (half-brain V69 Gy), respectively. Mean dose (equal to EUDV D with a = 1) of high-dose volume (V50 Gy-V60 Gy) was superior to traditional EUD and dose/volume points. CONCLUSION: Volume-effect parameter of EUD is variable and related to dose distribution. EUD with large low-dose volume may not be better than simple dose/volume points. Critical-dose-volume EUD could improve the predictive ability and has an invariant volume-effect parameter. Mean dose may be the case in which critical-dose-volume EUD has the best predictive ability.

Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes.

Context: Oridonin exhibits various pharmacological and physiological activities, including antioxidant, antibacterial, anti-inflammatory, pro-apoptotic, anticancer and neurological effects. However, its role in rheumatoid arthritis (RA) is yet to be revealed.Objective: We evaluated the effects of oridonin on the survival and autophagy of RA-fibroblast-like synoviocytes (FLSs).Materials and methods: RA-FLSs were treated with oridonin at serial concentrations of 0, 2, 4, 6, 8 and 10 µg/mL for 24, 48 and 72 h. Then, cell proliferation and apoptosis were measured. A GFP-LC3 plasmid was transfected into the cells to determine autophagy.Results: Oridonin suppressed RA-FLS proliferation in a dose-dependent manner. The half maximal inhibitory concentrations (IC50) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 µg/mL, respectively. Treatment with oridonin for 24 h increased apoptosis by 4.1%, and increased the protein levels of Bax and cleaved caspase-3 but significantly decreased the levels of IL-1ß in the culture supernatant (p < 0.05). In addition, 6 h of oridonin treatment significantly decreased the number of GFP-LC3 punctate dots and inhibited the protein levels of ATG5 and Beclin1 by 80.01% and 42.12%, respectively. Chloroquine (CQ) significantly reinforced the effects of oridonin on inhibition of autophagy, suppression of proliferation, and induction of apoptosis in RA-FLSs (p < 0.05).Conclusions: Our results indicate that treatment with oridonin in combination with CQ inhibits autophagy and cell proliferation and induces apoptosis in RA-FLSs more effectively than treatment oridonin alone. This finding indicates that oridonin is a potential therapeutic agent for RA.

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblastlike Synoviocytes in Patients with Rheumatoid Arthritis.

BACKGROUND: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. OBJECTIVE: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. METHODS: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1ß levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. RESULTS: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1ß secretion in RA-FLS. CONCLUSION: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

Aldehyde dehydrogenase 1 expression is correlated with poor prognosis in breast cancer.

Breast cancer (BC) is one of the most common cancers worldwide, and is a major cause of death in women. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells and cancer stem cells, and its activity correlates with the outcome of various tumors, including BC. This study aimed to analyze the relationship between ALDH1 expression and clinicopathological characters in BC and the prognostic significance of ALDH1.We used quantitative reverse-transcription PCR (qRT-PCR) to detect ALDHA1 mRNA levels in 25 fresh frozen BC samples and matched noncancerous samples. Immunohistochemistry on tissue microarrays was used to analyze protein expression in 137 paraffin-embedded BC tissues and corresponding noncancerous tissues. STATA 16.0 software was used for statistical analysis.The results suggested that levels of both ALDH1 mRNA and protein in BC were significantly higher than in corresponding adjacent breast samples (3.856 ±â€Š0.3442 vs 1.385 ±â€Š0.1534, P < .001; 52.6% vs 25.5%, P < .001, respectively). ALDH1 protein expression was also significantly associated with histological grade (P  =  .017), tumor size (P  =  .017), and tumor-node-metastasis (TNM) stage (P  =  .038). Multivariate analysis using the Cox regression model demonstrated that ALDH1 expression (P  =  .024), molecular typing (P  =  .046), and TNM classification (P  =  .034) were independent predictive factors for the outcome of BC. Kaplan-Meier analysis and the log-rank test indicated that patients with high ALDH1 expression, triple-negative BC, and advanced TNM stage had a reduced overall survival time.These data suggest that ALDH1 could be used as a prognostic factor for BC and may provide a useful therapeutic target in the treatment of BC.

Increased Expression of PHGDH and Prognostic Significance in Colorectal Cancer.

Phosphoglycerate dehydrogenase (PHGDH) plays an essential role in cancer-specific metabolic reprogramming. It has been reported as a putative metabolic oncogene in several types of human malignant tumors, such as breast cancer and melanoma. To date, PHGDH expression in colorectal cancer (CRC) as well as its association with clinicopathological characteristics and prognostic implication remain undetermined. In this study, we determined the PHGDH protein expression using tissue microarray immunohistochemistry (TMA-IHC) on 193 pairs of formalin-fixed, paraffin-embedded specimens of CRC and adjacent tissues, 25 chronic colitis, 41 low-, and 19 high-grade intraepithelial neoplasia specimens, and we also determined PHGDH mRNA level using quantitative reverse transcription PCR (qRT-PCR) on additional 23 pairs of fresh CRC tissues and adjacent tissues. We found that both PHGDH mRNA and protein was highly expressed in tumor tissues in comparison with matched adjacent non-tumor tissues, and high PHGDH protein expression was correlated with advanced TNM stage (P = .038) and larger tumor (P = .001). Multivariate Cox regression analysis showed that PHGDH protein expression (HR = 2.285, 95% CI = 1.18 to 4.41, P = .014), tumor differentiation (HR = .307, 95% CI = .154 to 0.609, P = .001), and TNM stage (HR = 1.791, 95% CI = 1.125 to 2.85, P = .014) were independent prognostic factors in CRC. Kaplan-Meier survival curves and log rank test showed that high PHGDH protein expression contributed to poor outcome in CRC patients (P < .001). In conclusion, these results suggest that assessment of PHGDH expression could be useful in identifying a high-risk subgroup of CRC.

Relationship between uptake of a radioiodinated quinazoline derivative and radiosensitivity in non-small cell lung cancer.

The aim of this study was to determine whether the uptake of radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy) quinazoline ([(125)I]PYK) could predict the response of non-small cell lung cancer (NSCLC) cells to radiotherapy in vitro. Four NSCLC cell lines, PC9, HCC827, A549, and H1975 were used. Cells were irradiated with doses ranging from 2 Gy to 8 Gy and/or exposed to 1 µM gefitinib. The effects of radiation and gefitinib were assessed by the CCK-8 assay and confirmed by reverse transcription-polymerase chain reaction and immunoflorescence microscopy. The uptake of [(125)I]PYK was determined by incubating cells with a tracer. The cell cycle was assessed by flow cytometry. The expression of EGFR was measured by western blotting. The results obtained revealed that the uptake of [(125)I]PYK was higher in PC9 and HCC827 cells than in A549 and H1975 cells. PC9 cells and HCC827 cells were also more radiosensitive than A549 and H1975 cells. The gefitinib pretreatment reduced the S phase fraction and enhanced radiation effects in PC9 and HCC827 cells. These results indicate that the uptake of [(125)I]PYK is related to the effects of radiation in NSCLC cells. Radioiodinated PYK may be useful in predicting the response of NSCLC in patients to radiotherapy.

[Status que of acupuncture for strephenopodia after stroke].

In order to optimize acupuncture protocol for stephenipodia after stroke, related papers of the recent 20 years are retrieved. Interrelated factors which may influence the therapeutic effect of acupuncture are analyzed through the aspects such as acupoints, needling methods and opportunities of acupuncture. It is held that importance should be attached on relation between acupoints and anatomy during acupoint selection. Different acupuncture protocol can be adopted in different phases of stephenipodia according to its time of occurrence. And it is found that the combination of acupuncture and rehabilitation can reinforce the therapeutic effect. Relationship between effect of acupuncture and patient's condition, acupoint selection and prescription, acupuncture manipulations (including directions, angles, reinforcing and reducing, quantity of stimulus) are worth to be further studied. On the base of the above all mentioned studies, optimization can be carried out on selection of acupoints and acupuncture manipulations. And therapeutic effect can be enhanced when the optimized acupuncture protocol is combined with rehabilitation therapies.

Enantioselective degradation of dufulin in four types of soil.

In this study, enantioselective degradation of dufulin in four types of soil (Guiyang silty loam, Nanning silty clay, Hefei silty clay, and Harbin silty clay) was investigated under sterile and nonsterile conditions. Pesticide residues in soil samples were extracted with acetonitrile. S-(+)-Dufulin and R-(-)-dufulin were separated and determined on an amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak IA) chiral column by normal phase high-performance liquid chromatography (HPLC). The absolute configurations of dufulin enantiomers were determined by obtaining experimental and computed circular dichroism spectra. Dufulin enantiomers were found to be configurationally stable in the selected soils, and no interconversion was observed during the incubation of enantiopure S-(+)- or R-(-)-dufulin under nonsterile conditions. Compared to the half-life (t1/2) of dufulin in sterile soils, the degradation rate was higher in nonsterile soils, which suggests that dufulin degradation can be attributed primarily to microbial activity in soils used for agricultural cultivation. Furthermore, enantiopure S-(+)-dufulin degraded more rapidly than its antipode. This suggests that use of enantiopure S-(+)-dufulin could exert less disturbance to soil bioactivity and contribute less to environmental pollution.

[The role of acupuncture and moxibustion in organized medicine of pain].

The literature on acupuncture-moxibustion and acupuncture-moxibustion combined with other therapies for all kinds of pain as well as organized medicine of pain in recent ten years are analyzed. It is found out that application of single acupuncture-moxibustion has positive effect on most of pain, while acupuncture-moxibustion combined with other therapies could improve the efficacy in a certain extent. The organized medical model of pain, by integration of clinical paths and optimization of medical methods, could achieve best effect on pain. With acupuncture-moxibustion joining in the organized medical model of pain, the analgesia effect could be enhanced, medical cost decreased and patient's life quality improved. The suitable disease, clinical path, action function and mechanism need further evidence-based research.

Reactivation of the homeotic tumor suppressor gene CDX2 by 5-aza-2'-deoxycytidine-induced demethylation inhibits cell proliferation and induces caspase-independent apoptosis in gastric cancer cells.

The DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) is widely used as an anticancer drug for the treatment of leukemia and solid tumors. Gastric cancer (GC) patients who were positive for caudal type homeobox transcription factor 2 (CDX2) expression showed a higher survival rate compared with those who were CDX2 negative, which suggests that CDX2 performs a tumor suppressor role. However, the molecular mechanisms leading to the inactivation of CDX2 remain unclear. In the present study we demonstrated that the expression levels of CDX2 and DNA methyltransferase enzyme 1 (DNMT1) mRNA were significantly higher in GC compared with distal non-cancerous tissue. The expression of CDX2 mRNA was significantly correlated with Lauren classification, TNM stage and lymph node metastasis. DNMT1 mRNA expression was significantly correlated with TNM stage, pathological differentiation and lymph node metastasis. The expression of CDX2 mRNA was inversely correlated with that of DNMT1 mRNA in GC. Hypermethylation of the CDX2 gene promoter region, extremely low expression levels of CDX2 mRNA and no expression of CDX2 protein were the characteristics observed in MKN-45 and SGC-7901 GC cell lines. Following the treatment of MKN-45 cells with 5-aza-CdR, the hypermethylated CDX2 gene promoter region was demethylated and expression of CDX2 was upregulated, while DNMT1 expression was downregulated. Furthermore, a concentration- and time-dependent growth inhibition as well as increased apoptosis were observed. Caspase-3, -8 and -9 activities increased in a concentration-dependent manner following exposure to different concentrations of 5-aza-CdR. Therefore, our data show that the overexpression of DNMT1 and methylation of the CDX2 gene promoter region is likely to be responsible for CDX2 silencing in GC. 5-Aza-CdR may effectively induce re-expression of the CDX2 gene, inhibit cell proliferation and enhance the caspase-independent apoptosis of MKN-45 cells in vitro.

Assessment of epidermal growth factor receptor status in glioblastomas.

OBJECTIVES: Our previous study showed that a newly designed tracer radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3'-iodophenoxy)quinazoline ([(125)I]PYK) is promising for the evaluation of the epidermal growth factor receptor (EGFR) status and prediction of gefitinib treatment of non-small cell lung cancer. EGFR is over-expressed and mutated also in glioblastoma. In the present study, the expressions and mutation of EGFR were tested with [(125)I] PYK in glioblastoma in vitro and in vivo to determine whether this could be used to predict the sensitivity of glioblastoma to gefitinib treatment. METHODS: Glioblastoma cell lines with different expression of EGFR were tested. Growth inhibition of cell lines by gefitinib was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Uptake levels of [(125)I]PYK were evaluated in cell lines in vitro. Tumor targeting of [(125)I]PYK was examined by a biodistribution study and imaging by single photon emission computed tomography (SPECT). RESULTS: High concentrations of gefitinib were needed to suppress EGFR-mediated proliferation. The uptake of [(125)I] PYK in cell lines in vitro was low, and showed no correlation with EGFR expression or mutation status. Biodistribution study and SPECT imaging with [(125)I]PYK for xenografts showed no [(125)I]PYK uptake. CONCLUSION: The results showed prediction of gefitinib effectiveness was difficult in glioblastoma by [(125)I]PYK, which might be due to the complicated expression of EGFR status in glioblastoma. Thus, new tracers for sites downstream of the mutant EGFR should be investigated in further studies.

[Expression of GC-C mRNA in peripheral blood mononuclear cells and its clinical roles in determining state of gastric cancer].

OBJECTIVE: To detect the expression of GC-C mRNA in peripheral blood of gastric carcinoma patients and determine its potential candidacy as a molecular biological marker for predicting the micrometastasis and determining the status of gastric cancer. METHODS: GC-C mRNA from peripheral blood samples of gastric carcinoma (n = 60), dysplastic (n = 21), intestinal metaplasia (n = 15) and healthy cases (n = 20) from November 2009 to August 2010 at Affiliated Hospital of Nantong University were assessed by real-time fluorescent quantitative PCR (RFQ-PCR). RESULTS: The expressions of GC-C mRNA in peripheral blood from patients with dysplasia, intestinal metaplasia and healthy controls were absent or very low. And a high level of GC-C mRNA was detected in the patients with gastric carcinoma than those with dysplastic and intestinal metaplasia, and the positive rate were 48.3% (29/60), 9.5% (2/21), 20.0% (3/15), respectively (all P < 0.05). The levels of GC-C mRNA were significantly correlated with Lauren typing, clinical stage, tumor differentiation degree, depth of invasion and lymph node metastasis (all P < 0.05). The GC-C mRNA expressions were positively correlated in peripheral blood and gastric carcinomas tissues (r = 0.4009, P = 0.0015). CONCLUSIONS: The over-expression of GC-C mRNA is found in peripheral blood from gastric carcinoma patients. Due to its close correlation with clinical stage and lymph node metastasis, it may become a potential prognostic marker of gastric carcinoma.