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ObjectiveTo understand the characteristics of genetic mutation in multiple primary lung cancer so as to guide clinical decisions in targeted therapy.MethodsWe analyzed a total of 265 tumors from 111 patients who underwent surgery for multiple lung cancers. Individual tumors were subjected to histological evaluation and gene mutation analysis using ABI 7500 Fluorescence quantitative PCR.ResultsIn this study, we analyzed demographic and clinical parameters such as age, gender, smoking, alcohol consumption, pathological type, number of nodules, and other details of 111 patients with early multiple primary lung cancer. We also compared the clinicopathologic characteristics of different populations based on the gene mutation status of pulmonary nodules. Subsequently, we performed a clinicopathological analysis of all 265 pulmonary nodules from these patients. Results showed significant differences in clinicopathological features of pulmonary nodules in different genetic mutations.ConclusionThis study revealed the gene mutation characteristics and clinicopathological features in early multiple primary lung cancer. We found that the gene mutation status between different nodules in patients with early multiple primary lung cancer was inconsistent in most cases. Therefore, the use of targeted therapy based on the genetic sequencing of only one nodule, is unreliable. We hope this study can be helpful in guiding clinical treatment decisions.

Supplementary Figure from Protein Phosphatase 2A–Dependent Mitotic hnRNPA1 Dephosphorylation and TERRA Formation Facilitate Telomere Capping

Background:: Citrus medica is a kind of medicinal and edible plant. It not only contains rich nutrients but also has a variety of therapeutic functions, including relieving pain, harmonizing the stomach, removing dampness, reducing phlegm, cleaning the liver, and relieving qi in traditional Chinese diagnosis. Methods:: The references of C. medica were mainly collected from the online database, such as PubMed, SciFinder, Web of Science, Google Scholar, Elsevier, Willy, SpringLink, and CNKI. The other related references were sorted by consulting books and documents. Results:: This review summarized and analyzed the different types of flavonoids of C. medica, including flavone-O-glycosides, flavone-C-glycosides, dihydroflavone-O-glycosides, flavonol aglycones, flavonoid aglycones, dihydroflavonoid aglycones, and bioflavonoids. The extraction methods of flavonoids were summarized in this review. Meanwhile, the multiple bioactivities of these flavonoids, including anti-atherosclerotic, hypolipidemic, anti-oxidant, hypoglycemic, and other activities. Their structure-activity relationships were reviewed and discussed in this paper. Conclusions:: This review summarized the different extraction methods of diverse flavonoids with multiple bioactivities of C. medica, and their structure-activity relationships were discussed in this paper. This review may provide a valuable reference for researching and exploiting C. medica.

The heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), telomeric repeat-containing RNA (TERRA), and protection of telomeres 1 (POT1) have been reported to orchestrate to displace replication protein A (RPA) from telomeric overhangs, ensuring orderly telomere replication and capping. Our previous studies further demonstrated that DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-dependent hnRNPA1 phosphorylation plays a crucial role in the promotion of hnRNPA1 binding to telomeric overhangs and RPA displacement during G2–M phases. However, it is unclear that how the subsequent exchange between hnRNPA1 and POT1 is orchestrated. Here we report that the protein phosphatase 2A (PP2A) depends on its scaffold subunit, which is called PPP2R1A, to interact with and dephosphorylate hnRNPA1 in the late M phase. Furthermore, PP2A-mediated hnRNPA1 dephosphorylation and TERRA accumulation act in concert to promote the hnRNPA1-to-POT1 switch on telomeric single-stranded DNA. Consequently, defective PPP2R1A results in ataxia telangiectasia and Rad3-related (ATR)-mediated DNA damage response at telomeres as well as induction of fragile telomeres. Combined inhibition of ATR and PP2A induces entry into a catastrophic mitosis and leads to synthetic lethality of tumor cells. In addition, PPP2R1A levels correlate with clinical stages and prognosis of multiple types of cancers. Taken together, our results indicate that PP2A is critical for telomere maintenance. Implications: This study demonstrates that the PP2A-dependent hnRNPA1 dephosphorylation and TERRA accumulation facilitates the formation of the protective capping structure of newly replicated telomeres, thus exerting essential oncogenic role in tumorigenesis.

Background Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. While it has been established that stereotactic body radiotherapy for NSCLC plays an important role in antitumor immune response, the possible effects of the dose rate on this response has not been fully clarified. Methods In vitro, A549 cells were irradiated on a Varian TrueBeam® Linear Accelerator with dose and dose rate escalation using the flattening filter-free (FFF) technique, which was followed by coculturing with peripheral blood mononuclear cells (PBMCs). The exosomes from irradiated A549 cells were isolated and then cocultured with PBMCs. Flow cytometry was performed to analyze the proportion of lymph cell clusters in PBMCs. Results The proportion of CD3− immune cell clusters in PBMCs was significantly higher in the 10 Gy treatment group than in the nonirradiated group and other lower-dose (2, 6 Gy) treatment groups at the dose rate of 1,000 MU/min. However, no influence was observed on the proportion of CD3+ T cell subsets. Further results showed that both natural killer (NK) and B cell proportions reached peaks in the 14 Gy treatment group when a dose rate of 1,200 MU/min was used. Notably, the peak values of these two cell proportions were reached at a lower radiation dose of 10 Gy when a greater dose rate, ranging from 1,600 to 2,400 MU/min, was used. We further found that a single, high dose of irradiation (10 Gy), as compared with a single, low dose of irradiation (2 Gy), could markedly stimulate the A549-related exosome secretion in a radiation dose rate-dependent manner. The ultrahigh dose rate radiation–derived exosomes contributed to the polarization of B and NK cell subsets in PBMCs. Conclusions The optimized radiation regime, which depends on the appropriate radiation dose and dose rate, results in the production of exosomes derived from NSCLC cells and eventually the redistribution of immune cells in PBMCs.

Background and purposeRadiotherapy (RT) is a double-edged sword in regulating immune responses. This study aimed to investigate the impact of thoracic RT on circulating eosinophils and its association with patient outcomes in non-small cell lung cancer (NSCLC).Materials and methodsThis retrospective study included 240 patients with advanced NSCLC treated with definitive thoracic RT from January 2012 to January 2020. Statistics included Kaplan-Meier analysis of overall survival (OS) and progression-free survival (PFS), multivariate Cox analyses to identify significant variables, and Spearman’s correlation to qualify the relationship between dose-volume histogram (DVH) parameters and EIR.ResultsAbsolute eosinophil counts (AECs) showed an increasing trend during RT and an obvious peak in the 1st month after RT. Thresholds of eosinophil increase ratio (EIR) at the 1st month after RT for both OS and PFS were 1.43. Patients with high EIR above 1.43 experienced particularly favorable clinical outcomes (five-year OS: 21% versus 10%, PConclusionEIR may serve as a potential biomarker to predict OS and PFS in NSCLC patients treated with RT. These findings require prospective studies to evaluate the role of such prognostic marker to identify patients at risk to tailor interventions.

Background: Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih (PTLCS) belongs to the family Compositae, which is a perennial medicinal plant mainly distributed in the Qinghai-Tibet Plateau of China. This review provides a comprehensive summary of the ethnopharmacology, phytochemistry, and pharmacology of PTLCS. This review offers valuable references and guidance for researching PTLCS in depth. Methods: The related references of PTLCS were retrieved from an online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. Results: PTLCS is widely reported for treating headaches, head injuries, traumatic injuries, anabrosis, impetigo, hepatitis, and other diseases in the medical field. Phytochemical research revealed that this plant contained flavonoid aglycones, flavonoid glycosides, xanthones, triterpenoids, coumarins, polyacetylenes, volatile oils, and other compounds. Meanwhile, PTLCS exhibited extensive pharmacological activities including anti-cardiac ischemia, anti-hypoxia, hepatoprotective, anti- inflammatory and analgesic, and antioxidant activities. Conclusions: PTLCS is widely used as a Tibetan medicine, which has a variety of chemicals with diverse bioactivities. Therefore, further studies are necessary to perform on the PTLCS to assay biological activities, discover their bioactive constituents, and reveal pharmacological mechanisms. This review may supply an important theoretical basis and valuable reference for in-depth research and exploitations of PTLCS.

Background: Highland barley Monascus purpureus Went, a traditional Tibetan medicine with food functions, which is fermented by Monascus purpureus with highland barley as substrate. It possesses various medical functions of promoting blood circulation and removing blood stasis, invigorating spleen and promoting digestion in folk of the Qinghai-Tibet Plateau in China. This review provides a comprehensive overview of ethnopharmacology, phytochemistry, and pharmacology of highland barley Monascus purpureus Went. Methods: The references of highland barley Monascus purpureus Went were retrieved from the online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. Results: Phytochemical research revealed that highland barley Monascus purpureus Went contained multiple chemical components, including Monascus pigments, monacolins, lactones, and other compounds. The reported pharmacological activities of highland barley Monascus purpureus Went included hypolipidemic, anti-nonalcoholic fatty liver disease, and hepatoprotective activities. Conclusions: In a word, botany, ethnopharmacology, phytochemistry and pharmacology of highland barley Monascus purpureus Went were reviewed comprehensively in this paper. In the future, highland barley Monascus purpureus Went needs further study, such as paying more attention to quality control and utilization of medicine. Therefore, this review may provide a theoretical basis and valuable data for future studies and exploitations on highland barley Monascus purpureus Went.

A high speed abrasive electrical discharge machining (AEDM-HS) process has been developed to improve the performance and save the machining energy of the conventional EDM process in machining particulate reinforced metal matrix composites (MMCs). The AEDM-HS process functions under a combined action of spark erosion and direct mechanical grinding. A set of experiments was conducted and the results showed that the material removal rate (MRR) of AEDM-HS was much higher than that of EDM under the experimental conditions of this study. Moreover, the surface roughness value (Ra) measured for the AEDM-HS specimen was about six times smaller than that of the specimen machined without high speed abrasive action (i.e., EDM alone). The material removal mechanism of this novel process has been analyzed by means of single-pulse experimentation. And the relative importance of the various processing parameters on MRR was established using orthogonal analysis. The results showed that the MRR is influenced by the machining factors in the order of duty cycle > current > pulse duration. This study showed that the AEDM-HS process is superior to the EDM process for machining particulate reinforced MMCs, where a higher machining efficiency and a better surface quality can be obtained.

In wire electro-discharge machining with an extremely high travelling speed of wire electrode (WEDM-HS), the emulsion is used as working liquid. Because there exists a functional electrolyte, the EDM spark can operate under a relatively large spark gap size condition, and this would facilitate the removal of machined debris. An investigation has been made into the machining feasibility when WEDM-HS has been employed to process Al2O3particle reinforced aluminum alloy 6061 with 10-vol% Al2O3(10ALO). And the material removal rate (MRR) has been examined in this study. Since there are many factors that can influence the MRR in the WEDM-HS process, in order to determine which is the most important factor and to optimize the machining parameters, the relative importance of the various machining parameters on material removal rate was established by utilizing an orthogonal experimental analysis. The results of the analysis suggest that to achieve a high MRR for particulate reinforced aluminum 6061 with 10-vol% Al2O3, the duty cycle is the most influential factor among current, pulse duration and duty cycle. And the impact of the different factors follows the sequence of duty cycle > current > pulse duration.

The X80 pipeline steel was welded with the way of submerged arc welding. The SST (slow strain test) of the welded joint samples in the air, NACE (National Association of Corrosion Engineers) solution (no H2S), NACE solution (saturated H2S) was performed to research the sensibility index of SCC (stress corrosion cracking) Iscc. The morphologies of the welded joint fractures and the fracture modes were observed with SEM (scanning electron microscope), and the fracture chemical compositions were analyzed with EDS (energy dispersive spectrometer), respectively. The fracture mechanisms of the welded joints were discussed. The results show that sensibility index of SCC in the air is not obvious, the fracture is dimple, and the mode of fracture is ductile fracture. The sensibility index of SCC in NACE solution (no H2S) is 13.21%, the stress corrosion is not obvious. The sample fracture shows quasi cleavage+dimple, and the fracture mode is toughness+brittle rupture. The sensibility index of SCC in NACE solution (saturated H2S) is 56.94%, the plastic loss is the most serious, appearing an obvious stress corrosion tendency, and there is no obvious necking phenomenon. The fracture mode is brittle fracture, and the sample fracture has a high sulfur concentration, prompting S to a aliquation of crisp crystal in the welded zone, and making its mechanical properties worsen.

Cancer stem cells (CSCs) are considered the source of the initial tumor formation and postoperative recurrence and metastasis. CD133(+) cells in hepatocellular carcinoma (HCC) display cancer stem-like properties and are thought to be responsible for chemoradioresistance. To explore the functional role of CD133 in liver cancer stem cells (LCSCs), we isolated CD133(+) cells from the HCC cell line HepG2, which were tested and confirmed to be CSC-like cells in HCC, downregulated CD133 expression in HepG2-CD133(+) cells by lentivirus-mediated short hairpin (shRNA) and analyzed the effects of CD133 on the modulation of stemness properties and chemoradiosensitivity in LCSCs. Our results showed that the in vitro cell proliferation, tumorsphere formation, colony formation and in vivo tumor growth in NOD/SCID mouse xenografts of LCSCs were significantly repressed after CD133 silencing. We also found that suppression of CD133 enhances the sensitivity of LCSCs to chemotherapy and radiotherapy. Knockdown of CD133 reduced G0/G1 phase cells and increased cellular apoptosis via modulation of Bcl-2 and Bax. Collectively, the stem-targeted therapy via CD133 could provide a novel strategy for the treatment of HCC.

Hydroxyapatite (HA)-zirconium (ZrO 2 ) composite coating was produced by magnetic sputtering on Ti6Al4V titanium alloy substrate, the coatings of 50HA-50ZrO 2 and 75HA-25ZrO 2 (mass fraction, %) were characterized by scanning electron microscopy, energy disperse spectroscopy, X-ray diffraction and scratch test, respectively, and the effects of HA contents in the coating on residual stress were analyzed. The experimental results show that the phases of HA-ZrO 2 composite coatings are HA, ZrO 2 and Y 2 O 3 , and the HA has a certain decomposition in the combination process, producing TCP and CaO impurity phases. The porous surface of coating is conducive to the growth of bone tissue, and the surface roughness values of 50HA-50ZrO 2 and 75HA-25ZrO 2 are 1.61 μm and 2.92 μm, respectively. The coating interface is of mechanical integration, the bonding strength values of 50HA-50ZrO 2 and 75HA-25ZrO 2 are 30 N and 17.5 N, respectively, showing a downward trend with the HA contents increasing. The residual stress values in the coating of 50HA-50ZrO 2 and 75HA-25ZrO 2 are (−399.1±3.0) MPa, (−343.2±20.3) MPa, respectively, as a result, the appropriate increase of HA contents in the coating will reduce its residual stress.

The purpose of this study is to answer the question: Is personality pattern of “good teacher” quite different from the one of “bad teacher”? The study deals with the personality pattern of “bad teacher” and “good teacher”. The subject investigated was 526 teachers from a local university; the sample is 204 of them, which is divided into two parts, “bad teacher” and “good teacher”. Eysenck Personality Questionnaire for Adult (EPQ) was used in the study. It was shown that personality pattern of “good teacher” is not quite different from the one of “bad teacher” in the aspect of extroversion, neuroticism, psychoticism and dissimulation. There aren’t statistic significant differences between the personality pattern of “bad teacher” and “good teacher”.

Everolimus has no nephrotoxicity and is used to treat patients with post-liver transplant chronic renal insufficiency. The present systematic review was to evaluate the efficacy and safety of everolimus in de novo liver transplant patients.Randomized controlled trials comparing everolimus for de novo liver transplant in PubMed, the Cochrane Library, and ScienceDirect published up to March 31, 2014 were searched by two independent reviewers. Mean differences and 95% confidence interval (95% CI) for renal function, relative risk (RR) and 95% CI for treated biopsy-proven acute rejection (tBPAR), graft loss, death, neoplasms/tumor recurrence, and adverse events were collected. Meta-analyses were performed with RevMan version 5.10.A total of four randomized controlled trials covering 1119 cases were included. The meta-analyses revealed that compared with standard exposure of calcineurin inhibitors (CNIs), everolimus combined with reduced CNIs improved creatinine clearance (calculated with the Cockcroft-Gault formula) by 5.13 mL/min at one year (95% CI: 0.42-9.84; P=0.03), and decreased tBPAR (RR: 0.56; 95% CI: 0.35-0.90; P=0.02). Everolimus initiation with CNIs elimination improved glomerular filtration rate (GFR, measured with the modification of diet in renal disease formula) of 10.42 mL/min/1.73 m2 (95% CI: 3.44-17.41; P0.01) one year after treatment, but increased tBPAR (RR: 1.71; 95% CI: 1.15-2.53; P0.01). Everolimus decreased the risk of neoplasms/tumor recurrence after liver transplant (RR: 0.60; 95% CI: 0.34-1.03; P=0.06), but was associated with greater risk of adverse events which resulted in drug discontinuation (RR: 1.98; 95% CI: 1.49-2.64; P0.01).Early introduction of everolimus combined with low-dose or no CNI in de novo liver transplant significantly improves renal function one year post treatment. Everolimus combined with low-dose CNI decreases the risk of tBPAR one year after liver transplant, but everolimus administered without CNIs increases tBPAR.

AIM:To investigate the killing effect of carcinoembryonic antigen (CEA) and tissue-specific cytosine deaminase (CD)/5fluorocytosine (5-FC) system on human colorectal carcinoma cell lines LoVo and SW480 in vitro. METHODS:Recombinant retroviral vector G1CEACDNa was constructed,in which the CD gene was controlled under the CEA promoter, and retroviral vector pCD2 were introduced through liposome technique respectively to the human colorectal carcinoma cell lines LoVo and SW480. Expression of CEA was high and low in both the cell lines respectively. The cells were selectively cultured in G418. The proliferative colonies were treated with 5-FC. RESULTS:After the transfection, LoVo-CEACD cells and LoVo-CD cells were more sensitive to 5-FC than their parental cells (P

Protein kinases of the microtubule affinity-regulating kinase (MARK) family were originally discovered because of their ability to phosphorylate certain sites in tau protein (KXGS motifs in the repeat domain). This type of phosphorylation is enhanced in abnormal tau from Alzheimer brain tissue and causes the detachment of tau from microtubules. MARK-related kinases (PAR-1 and KIN1) occur in various organisms and are involved in establishing and maintaining cell polarity. Herein, we report the ability of MARK2 to affect the differentiation and outgrowth of cell processes from neuroblastoma and other cell models. MARK2 phosphorylates tau protein at the KXGS motifs; this results in the detachment of tau from microtubules and their destabilization. The formation of neurites in N2a cells is blocked if MARK2 is inactivated, either by transfecting a dominant negative mutant, or by MARK2 inhibitors such as hymenialdisine. Alternatively, neurites are blocked if the target KXGS motifs on tau are rendered nonphosphorylatable by point mutations. The results suggest that MARK2 contributes to the plasticity of microtubules needed for neuronal polarity and the growth of neurites.

It has been proposed that the Notch signaling pathway may serve a pivotal role in cellular differentiation, proliferation and apoptosis. However, the function of Notch signaling in gastric cancer stem cells (GCSCs) is largely unknown. The present study aimed to delineate the role of the Notch1 pathway in GCSCs and during epithelial-mesenchymal transition (EMT). Flow cytometry was used to isolate CD44+ cells from the human gastric cancer cell line, MKN45. CD44+ cells displayed the characteristics of CSCs and exhibited higher Notch1 expression compared with CD44− cells. To investigate the role of the Notch1 pathway in GCSCs, CD44+ cells were treated with the γ-secretase inhibitor DAPT. DAPT treatment inhibited the expression of the Notch1 downstream target Hes1 and EMT markers, suppressed the properties of CSCs and impaired the invasion and proliferation capabilities of CD44+ cells. In addition, intraperitoneal treatment with DAPT effectively inhibited the growth of CD44+ cell xenograft tumors. The present study indicated that CD44+ GCSCs possess the characteristics of CSCs and that the Notch1 pathway serves a critical role in the maintenance of CSCs and EMT.

The bis-indole indirubin is an active ingredient of Danggui Longhui Wan, a traditional Chinese medicine recipe used in the treatment of chronic diseases such as leukemias. The antitumoral properties of indirubin appear to correlate with their antimitotic effects. Indirubins were recently described as potent (IC(50): 50-100 nm) inhibitors of cyclin-dependent kinases (CDKs). We report here that indirubins are also powerful inhibitors (IC(50): 5-50 nm) of an evolutionarily related kinase, glycogen synthase kinase-3beta (GSK-3 beta). Testing of a series of indoles and bis-indoles against GSK-3 beta, CDK1/cyclin B, and CDK5/p25 shows that only indirubins inhibit these kinases. The structure-activity relationship study also suggests that indirubins bind to GSK-3 beta's ATP binding pocket in a way similar to their binding to CDKs, the details of which were recently revealed by crystallographic analysis. GSK-3 beta, along with CDK5, is responsible for most of the abnormal hyperphosphorylation of the microtubule-binding protein tau observed in Alzheimer's disease. Indirubin-3'-monoxime inhibits tau phosphorylation in vitro and in vivo at Alzheimer's disease-specific sites. Indirubins may thus have important implications in the study and treatment of neurodegenerative disorders. Indirubin-3'-monoxime also inhibits the in vivo phosphorylation of DARPP-32 by CDK5 on Thr-75, thereby mimicking one of the effects of dopamine in the striatum. Finally, we show that many, but not all, reported CDK inhibitors are powerful inhibitors of GSK-3 beta. To which extent these GSK-3 beta effects of CDK inhibitors actually contribute to their antimitotic and antitumoral properties remains to be determined. Indirubins constitute the first family of low nanomolar inhibitors of GSK-3 beta to be described.

Paullones constitute a new family of benzazepinones with promising antitumoral properties. They were recently described as potent, ATP-competitive, inhibitors of the cell cycle regulating cyclin-dependent kinases (CDKs). We here report that paullones also act as very potent inhibitors of glycogen synthase kinase-3b (GSK-3b) (IC50: 4‐80 nm) and the neuronal CDK5/p25 (IC50: 20‐200 nm). These two enzymes are responsible for most of the hyperphosphorylation of the microtubule-binding protein tau, a feature observed in the brains of patients with Alzheimer’s disease and other neurodegenerative ‘taupathies’. Alsterpaullone, the most active paullone, was demonstrated to act by competing with ATP for binding to GSK-3b. Alsterpaullone inhibits the phosphorylation of tau in vivo at sites which are typically phosphorylated by GSK-3b in Alzheimer’s disease. Alsterpaullone also inhibits the CDK5/p25-dependent phosphorylation of DARPP-32 in mouse striatum slices in vitro. This dual specificity of paullones may turn these compounds into very useful tools for the study and possibly treatment of neurodegenerative and proliferative disorders.

The rapid development of wind farms construction, wind resource assessment is correct or not directly affect the future effectiveness of wind farms is good or bad. Wind resources in the slope of the windward slope, the wind speed “climbing effect” makes the wind velocity increases.On the windward slope, the wind resource at each location varied widely. Therefore, the windward slope actual wind speed at any position have to use the measured data at the bottom and top of mountains according to wind speed changes of slope to Calculate. This article discusses how to obtain more actual wind speed at distances on different slope and the slope of at each location.

In the title compound, C10H8N2O2S, the planes of the aromatic rings are oriented at a dihedral angle of 66.69 (3)°. In the crystal structure, intermolecular N—H...N and C—H...O interactions link the molecules into a two-dimensional network, forming R22(8) ring motifs. π–π contacts between the thiazole rings [centroid–centroid distance = 3.535 (1) Å] may further stabilize the structure. A weak C—H...π interaction is also found.

To investigate the interference and the mechanisms of Bcl-2 and HER-2 genes antisense oligodeoxynucleotides combined transfection in the human tongue carcinoma Tca8113 cell lines.There were 6 groups in our study, normal control group, Bcl-2 sense experimental group, HER-2 sense experimental group, Bcl-2 antisense experimental group, HER-2 antisense experimental group, Bcl-2 and HER-2 genes antisense oligodeoxynucleotides combined transfection experimental group. In the different times after liposome-mediated transfection, the cell apoptosis, Bcl-2 and HER-2 expressing level were observed by RT-PCR and electronic microscope.According to the results of combined transfection experimental group, the apoptosis body and apoptosis cells were observed. The expression of genes were decreased statistically in both Bcl-2 and HER-2, respectively. Bcl-2 and HER-2 combined ASODN was superior to single ASODN in the intervention of tongue carcinoma.Bcl-2 and HER-2 ASODN can effectively interfere the expression of HER-2 and Bcl-2 genes. The expression of HER-2 and Bcl-2 can be reduced, and the apoptosis of cells can be enhanced.

It was reported previously that genistein could inhibit proliferation of human ovarian carcinoma cell line SKOV(3), but mechanism was not clear. There is a close relationship between EGFR mediated signal transduction pathway and the development of ovarian tumor. This study aimed to investigate the effects of genistein on the EGFR mediated signal transduction pathway and to clarify its mechanisms of proliferation inhibition on human ovarian carcinoma cell line SKOV(3) and its xenograft in nude mice.The expression of c-erbB-2 protein was determined using immunocytochemistry. The expressions of c-jun and c-fos protein were determined using Western blotting. The expression of c-erbB-2, c-raf-1, c-jun and c-fos mRNA were tested by reverse transcription-polymerase chain reaction (RT-PCR).The expression of c-erbB-2, c-raf-1 and its downstream gene c-jun and c-fos were decreased at mRNA level in the 20 micromol/L genistein group. The expression of c-erbB-2 protein were decreased, its average absorbency (A) were decreased after treatment of SKOV(3) with 20 micromol/L genistein for 48 h, reached at 0.42 +/- 0.02 (P0.05). Western blotting demonstrated that the expressions of c-jun and c-fos protein were decreased gradually after being treated with 20 micromol/L genistein for 12 - 72 h.Genistein could down-regulate the expression of two key genes, c-erbB-2 and c-raf-1 at mRNA and protein level in the EGFR mediated signal transduction pathway, and down-regulate the expression of its downstream nuclear transcription factors c-jun and c-fos at mRNA and protein level. It is suggested that interfering the expressions of some key signal molecules in EGFR mediated signal transduction system by genistein may account for its molecular foundation of proliferation inhibition in ovarian carcinoma.

Although many positive studies were reported on single C-erbB-2 or C-raf-1 antisense oligodeoxynucleo- tide (ASODN) in cancer treatment, these studies were usually limited in single gene or in cell level and were not appropriate according to the multiple genes hypotheses of tumorigenesis. This study was designed to investigate the effects of C-erbB-2 and C-raf-1 combined with ASODN on the treatment of ovarian carcinoma xenograft in nude mice.The model of xenografts derived from ovarian epithelial cancer SKOV3 cells was established in Balb/C nude mice, then they were randomly divided into a negative control group and 6 experimental groups [intraperitoneal injection of (1)liposome-C-erbB-2-ASODN, (2)liposome- C-raf-1-ASODN, (3)liposome-C-erbB-2-ASODN, (4)liposome-C-raf-1-ASODN, (5)whole-dose combined ASODN, (6)half-dose combined ASODN. The weight of nude mice and tumor volume were measured. The tumor growth inhibitory rates and the tumor volume decreased rates were calculated.C-erbB-2 and C-raf-1 combined with ASODN exhibited potent tumor growth inhibition. The tumor volume inhibitory rates were 72.5% and 78.4%; the tumor weight inhibitory rates were 70.7% and 75.3%; the tumor volume decreased rates were 29.7% and 41.6% for whole-dose combined group and half-dose combined group post-experiment, respectively. Of the 7 groups, there was no significant difference on nude mice weight post-experiment and therefore the toxicity was endurable.C-erbB-2 and C-raf-1 combined with ASODN showed potent tumor growth inhibition in vivo.

To investigate the inhibition effects of c-erbB-2 and c-raf-1 antisense oligodeoxynucleotides (ASODN) combined transfection on the human ovarian epithelial cancer transplanted subcutaneously in nude mice.There were 7 groups: normal control group, c-erbB-2 sense observed group, c-raf-1 sense observed group, c-erbB-2 antisense observed group, c-raf-1 antisense observed group, whole dose combined group, half dose combined group. Human ovarian epithelial cancer cells SKOV3 were treated by different oligodeoxynucleotides, then transplanted subcutaneously in nude mice, respectively. The changes of tumor volume were observed and the tumor growth inhibitory rate was calculated.There was no difference between sense observed group and normal control group. There was a larger growth inhibitory rate in whole -dose combined group and half -dose combined group, the first time that can be detected was 13.7 days and 15.2 days, and the maximum tumor growth inhibitory rates were 61.1% and 71.3%, respectively.The results suggested that ASODN combined transfection can inhibit the tumorigenesis of ovarian epithelial cancer cells in nude mice, it may be a more useful gene therapy for the ovarian epithelial carcinoma.

In the crystal structure of the title phospho­nium salt, C22H22O2P+·Br−·H2O, the triphenyl­phospho­sphonium group has three P—C bonds to phenyl rings which are equal within experimental error [mean 1.782 (3) A] The P atom is also attached directly to the C atom of a 1,3-dioxan-2-ylmethyl group with a longer P—C bond of 1.800 (3) A. The C—C bond of the dioxane ring [1.418 (5) A] is shorter than the normal bond distance. The asymmetric unit contains two bromide anions on twofold rotation axes to balance the charge of the cation.

In the molecule of the title compound, C12H16N2O4, an intramolecular N—H...O hydrogen bond results in the formation of a six-membered ring having an envelope conformation. In the crystal structure, a bifurcated intra/intermolecular N—H...(O,O) hydrogen bond generates inversion dimers.

In the molecule of the title compound, C14H12N2O4, the aromatic rings are oriented at a dihedral angle of 51.50 (4)°. An intramolecular N—H...O interaction results in the formation of a six-membered ring having an envelope conformation. In the crystal structure, intermolecular N—H...O interactions link the molecules into centrosymmetric dimers. π–π contacts between the benzene rings [centroid–centroid distance = 3.708 (1) Å] may further stabilize the structure.