Alteration of gene expression profiling including GPR174 and GNG2 is associated with vasovagal syncope.

Vasovagal syncope (VVS) causes accidental harm for susceptible patients. However, pathophysiology of this disorder remains largely unknown. In an effort to understanding of molecular mechanism for VVS, genome-wide gene expression profiling analyses were performed on VVS patients at syncope state. A total of 66 Type 1 VVS child patients and the same number healthy controls were enrolled in this study. Peripheral blood RNAs were isolated from all subjects, of which 10 RNA samples were randomly selected from each groups for gene expression profile analysis using Gene ST 1.0 arrays (Affymetrix). The results revealed that 103 genes were differently expressed between the patients and controls. Significantly, two G-proteins related genes, GPR174 and GNG2 that have not been related to VVS were among the differently expressed genes. The microarray results were confirmed by qRT-PCR in all the tested individuals. Ingenuity pathway analysis and gene ontology annotation study showed that the differently expressed genes are associated with stress response and apoptosis, suggesting that the alteration of some gene expression including G-proteins related genes is associated with VVS. This study provides new insight into the molecular mechanism of VVS and would be helpful to further identify new molecular biomarkers for the disease.

Impact of smoking status and pathologic type on epidermal growth factor receptor mutations in lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in lung carcinomas can make the disease more responsive to the treatment with tyrosine kinase inhibitors. We aimed to evaluate the prevalence of EGFR mutations in a large series of lung carcinomas. METHODS: We examined 1195 consecutive lung cancer patients for EGFR mutations in exons 18, 19, and 21 using direct sequencing of polymerase chain reaction products. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit > 1 year ago), or current smokers (quit < 1 year ago). RESULTS: There were EGFR mutations in 9 (4.5%) of 201 squamous carcinomas, in 1 (2%) of 50 large cell carcinomas, and in 1 (2.3%) of 44 small cell carcinomas that were investigated. Three hundred and twenty-seven mutations were found in the series of 858 adenocarcinomas (38.1%). Among 858 lung adenocarcinomas, we detected EGFR mutations in 250 (48.6%) of 514 never smokers, 39 (33.9%) of 115 former smokers, and 38 (16.6%) of 229 current smokers. Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P = 0.0002) or stopped smoking less than 15 years ago (P = 0.033) compared with individuals who never smoked. CONCLUSIONS: Adenocarcinoma is the most frequent EGFR mutation pathologic type in lung cancer. The likelihood of EGFR mutations in exons 18, 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 15 years ago. These data can assist clinicians in assessing the likelihood of exons 18, 19, or 21 EGFR mutations in Chinese patients with lung cancer when mutational analysis is not feasible.

[A diagnostic model of cerebrospinal protein fingerprint pattern for brain metastases of non-small cell lung cancer].

OBJECTIVE: To establish a diagnostic model of protein fingerprint pattern in the cerebrospinal fluid (CSF) for non-small-cell lung cancer (NSCLC) patients with brain metastases. METHODS: The CSF samples were obtained from 29 NSCLC patients with brain metastasis, 23 non-tumor patients and 10 early-stage NSCLC patients without brain metastases for analysis of the protein expression profiles using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). The data were then analyzed by Biomarker Wizard software, and the tree analysis patterns were generated using the decision-tree model in Biomarker Patterns software. The diagnostic model was tested for its clinical application. RESULTS: Five protein peaks were identified showing differential expression between patients with brain metastases and those without brain metastases. Combination of the 3 protein peaks (m/z: 8698.00, 1215.32 and 1245.70) could discriminate these two samples with a sensitivity of 100.00% (29/29) and a specificity of 100.00% (23/23). Five proteins were differentially expressed between the NSCLC patients with brain metastases and the non-tumor patients. With one protein peak (m/z: 6050.00), these two samples could be discriminated with a sensitivity of 90.00% (9/10) and a specificity of 78.26% (18/23). CONCLUSION: The established diagnostic model of CSF protein fingerprint pattern provides high sensitivity and specificity in the diagnosis of NSCLC with brain metastasis.

[Association between the polymorphism of GNB3C825T gene and vasovagal syncope in children].

OBJECTIVE: Investigate the association between GNB3C825T gene polymorphism and pediatric vasovagal syncope. METHOD: Syncope group consisted of 54 cases of unexplained syncope in children, including 18 males and 36 females, at the age of 11.8 years; control group consisted of 54 healthy children over the same period, of whom 20 were male and 34 female, at the age of 11.2 years. The patients underwent head-up tilt test (HUTT). According to HUTT test results, HUTT-positive group and HUTT-negative group were further classified. For cases in HUTT-positive group, based on the changes in blood pressure and in heart rate during HUTT, vasodepressor, mixed and cardioinhibitory patterns were studied. DNA was extracted from peripheral blood in all the patients. A pair of primers was designed flanking 825 polymorphic loci. Products were recovered by using polymerase chain reaction (PCR). GNB3C825T polymorphism was detected by using gene-side GNB3C825T sequencing. Allele distribution between the various groups were studied. RESULT: Among fifty-four children with syncope, HUTT was positive in 30 cases, including vasodepressor pattern in 15 cases (50.0%), mixed pattern in 9 cases (30.0%) and cardioinhibitory pattern in 6 cases (20.0%). Whereas the subjects in control group had negative HUTT response. GNB3C825T allele C in the control and syncope groups was 81.5% and 65.7%, respectively. GNB3C825T allele T in the control and syncope groups was 18.5% and 34.3%, respectively (χ(2) = 6.888, P < 0.05). GNB3C825T allele C in HUTT-positive and negative groups was 61.7% and 81.3%, respectively. And GNB3C825T allele T in HUTT-positive and negative groups was 38.3% and 18.7%, respectively (χ(2) = 4.905, P < 0.05). GNB3C825T allele frequency did not show statistically significant difference among the 3 hemodynamic patterns of VVS (χ(2) = 0.658, P > 0.05). CONCLUSION: Study on GNB3C825T allele frequency in children with vasovagal syncope is of significant value for a better understanding of the pathophysiology of VVS and provide a molecular biologic basis for its mechanisms.

[Protective effect of Oviductus Ranae capsules on the reproductive organs of aged mice].

OBJECTIVE: To observe the protective effect of Oviductus Ranae (OR) capsules on the reproductive organs in an aged mouse model established by D-galactose injection. METHODS: Forty-eight female Kunming mice were randomly divided into 4 equal groups, namely the high- and low-dose OR groups, diethylstilbestrol (DT) group, and model group. The mice received subcutaneous injection of D-galactose for 6 weeks to establish aging models. Another 12 mice were injected daily with normal saline (NS) to serve as the normal control group. From the third week of the experiment, the mice were given oral OR at low or high doses (in the OR groups) or vegetable oil (in the model or control groups) till the sixth week. In the last two weeks, the vaginal smears were obtained from the mice for evaluating the changes of the vaginal keratinocytes and counting the days of estrus. After completion of drug administration, all the mice were sacrificed and the serum content of estradiol (E(2)) was detected by radioimmunoassay, with the ovarian and uterine indices determined. The ovarian and uterine pathologies were observed using HE staining, and SOD and MDA activities in the ovary and uterus were also assessed. RESULTS: OR obviously increased E(2) level and the ovarian and uterine indices in the aged mice, also alleviating the pathological change of the ovary and uterus. OR substantially depressed MDA content and enhanced SOD activity in the ovary and uterus. CONCLUSION: OR has definite antioxidative effects and ameliorates the degenerative changes of the reproductive organs in mouse models of aging.

Weekly gemcitabine as a radiosensitiser for the treatment of brain metastases in patients with non-small cell lung cancer: phase I trial.

BACKGROUND: Conventional treatment for non-small cell lung cancer (NSCLC) brain metastases (BM) is whole-brain radiotherapy (WBRT). The efficacy is limited. It might be increased by a potent radiosensitizer such as gemcitabine, which is believed to cross the disrupted blood-brain barrier. The primary objective of this study was to determine the maximum tolerated dose (MTD) of weekly gemcitabine given concurrently with WBRT. METHODS: Patients with BM from NSCLC were included. The dose of WBRT was 3750 cGy (total 15 times, 3 weeks). Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting dose was 400 mg/m(2), escalated by 100 mg/m(2) increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4 hematological or grade 2 neurological toxicity. When two or more patients experience DLT, the MTD was reached. RESULTS: A total of 16 patients were included; 69% had a performance status (PS) 1 (Eastern Cooperative Oncology Group, ECOG). A total of 69% had concurrent active extra cranial diseases. All had more than 3 BM. Up to 600 mg/m(2) (level 3) no neurology toxicity was observed. At 600 mg/m(2) two out of 9 patients developed grade 4 thrombocytopenia. One of the two patients' thrombocytopenia was confused with disseminated intravascular coagulation (DIC). At 700 mg/m(2) two out of 4 patients developed neurotoxicities. One developed grade 3 seizure and cognitive disorder. Another patient developed suspected grade 2 muscle weakness. CONCLUSIONS: The MTD was reached at a dose of 700 mg/m(2). The dose of 600 mg/m(2) would be considered for further study.

[Gefitinib target treatment in non-small cell lung cancer].

OBJECTIVE: To evaluate the efficacy, target population and influencing factors of Gefitinib in patients with non-small-cell lung cancer (NSCLC) pretreated with platinum. METHODS: Patients with NSCLC who had been previously treated with at least one course of platinum based chemotherapy received 250 mg oral doses of Gefitinib once daily till disease progression. Response rate, progression free survival, overall survival and toxicity profile were analyzed. Kaplan-Meier method was used to analyze the survival rate. Cox regression was used to define the predictive factors. RESULTS: A hundred and fifteen patients were enrolled into the study from July 2001 to May 2005. The follow-up was ended on Sep. 30, 2006. Median follow up time was 30 months. The compliance rate was 100%. The median symptom improving time was 8 days. Complete response rate was 4.3% (5/115), partial response 39.1% (45/115), stable disease 27.0% (31/115) and progressive disease 29.6% (34/115). Response rate was 43.5% (50/115). Disease control rate was 70.4% (81/115). The median progression-free survival and median overall survival were 8 and 11 months, respectively. One and two-year progression-free survival rates and overall survival rates were 32.2% (events 78), 5.6% (events 103) and 41.7% (death 67), 21.5% (death 87) respectively; 3-year overall survival 12.3% (death 93). Adenocarcinoma was the only predictor for therapeutic effect in the Cox model (P = 0.004). The primary failure to gefitinib was due to brain metastasis (39.4%, 28/71). Grade III skin toxicity was found in 5.2% (6/115) patients. CONCLUSION: Gefitinib is the drug of choice for patients with heavily pretreated stage III(B) and IV adenocarcinoma of NSCLC with safe and accepted toxicity profile.

[Relationship of the curative effects of gefitinib on non-small cell lung carcinoma to gender and to epithelial growth factor receptor status].

OBJECTIVE: To investigate the mutation of epithelial growth factor receptor (EGFR) gene in the non-small cell lung carcinoma (LSCLG) patients with different genders and the relationship between the gender of LSCLG patients and the curative effects of gefitinib, an specific tyrosine kinase. METHODS: Tumor specimens were obtained from 135 NSCLC patients, 94 males (78.7% smoking) and 41 females (17.1% smoking), of which 20 received gefitinib treatment after the failure of chemotherapy, during operation and stored at -80 degrees C. The genomic DNA of the cancer tissues was extracted by using Trizol reagent. Nest-PCR was used to amplify the exons 18, 19, and 21 of the EGFR gene and the PCR products were purified by agarose electrophoresis and then sequenced. RESULTS: EGFR mutation was found in 29 of the 135 NSCLC patients (21.5%), with a mutation rate of 19.1% in the males and a mutation rate of 26.8% in the females (P = 0.344). The mutation types included G719C and G719V in exon 16, delE746 - 750, and delE746 - 751 in exon 19, and L858R and L861Qin exon 21. Among the 20 patients who received gefitinib treatment the disease control rate was 85% (17/20), being 76.9% in the male patients (10/13) and being 100% in the female patients (7/7) (P = 0.521). There were not significant differences in the mean time-to-progression (TTP) between the male and female patients (9 months vs. 14 months, P = 1), and between the patients with the wild type of EGFR gene and those with the mutated type of gene (9 months vs. 14 months, P = 1). CONCLUSION: There is no significant relationship between the curative effect of gefitinib on NSCLC and gender and EFGR status.