STS â ¡A inhibited angiogenesis of lung adenocarcinoma by activating FOXO3 to inhibit CXCL1/STAT3/VEGF pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Sulfotanshinone IIA sodium (STS IIA) has been proven to have an anticancer effect. However, its role in LUAD and its underlying mechanism remain unclear. OBJECTIVE: To investigate the role and mechanism of STS IIA in LUAD angiogenesis. METHODS: The mRNA levels of genes, including forkhead box O3 (FOXO3) and chemokine C-X-C motif ligand 1 (CXCL1), were detected by qRT-PCR. The levels of proteins, including FOXO3, CXCL1, and vascular endothelial growth factor (VEGF), were measured by Western blot. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by the EdU assay and the tubule formation assay, respectively. The binding relationship between FOXO3 and CXCL1 was detected by dual-luciferase reporter assay. RESULTS: Our results illustrated that different concentrations of STS IIA inhibited the proliferation and angiogenesis of HUVECs. FOXO3 regulated the proliferation and angiogenesis of HUVECs inhibited by STS ⅡA via targeting CXCL1. Subsequently, we proved that exogenous CXCL1 alleviated the inhibition of proliferation and angiogenesis of HUVECs regulated by STS IIA via activating the STAT3/VEGF pathway. Finally, we found that STS IIA inhibited the angiogenesis of lung adenocarcinoma though FOXO3 to inhibit the CXCL1/STAT3/VEGF pathway. CONCLUSION: Our study finally elucidated the underlying molecular mechanism by which STS ⅡA inhibits LUAD angiogenesis.

A trade-off between leaf hydraulic efficiency and safety across three xerophytic species in response to increased rock fragment content.

Limited information is available on the variation of plant leaf hydraulic traits in relation to soil rock fragment content (RFC), particularly for xerophytes native to rocky mountain areas. In this study, we conducted a field experiment with four gradients of RFC (0, 25, 50 and 75% ν ν-1) on three different xerophytic species (Sophora davidii, Cotinus szechuanensis and Bauhinia brachycarpa). We measured predawn and midday leaf water potential (Ψleaf), leaf hydraulic conductance (Kleaf), Ψleaf induced 50% loss of Kleaf (P50), pressure-volume curve traits and leaf structure. A consistent response of hydraulic traits to increased RFC was observed in three species. Kleaf showed a decrease, whereas P50 and turgor loss point (Ψtlp) became increasingly negative with increasing RFC. Thus, a clear trade-off between hydraulic efficiency and safety was observed in the xerophytic species. In all three species, the reduction in Kleaf was associated with an increase in leaf mass per area. In S. davidii, alterations in Kleaf and P50 were driven by leaf vein density (VLA) and Ψtlp. In C. szechuanensis, Ψtlp and VLA drove the changes in Kleaf and P50, respectively. In B. brachycarpa, changes in P50 were driven by VLA, whereas changes in both Kleaf and P50 were simultaneously influenced by Ψtlp. Our findings suggest that adaptation to increased rockiness necessarily implies a trade-off between leaf hydraulic efficiency and safety in xerophytic species. Additionally, the trade-off between leaf hydraulic efficiency and safety among xerophytic species is likely to result from processes occurring in the xylem and the outside-xylem hydraulic pathways. These findings contribute to a better understanding of the survival strategies and mechanisms of xerophytes in rocky soils, and provide a theoretical basis for the persistence of xerophytic species in areas with stony substrates.

Age Determination and Growth Characteristics of the Potentilla griffithii: A Comparison of Two Different Habitats in Western Sichuan Plateau, China.

This study proposes a rapid and non-destructive technique for determining the age of Potentilla griffithii individuals in the field by observing the sequence of leaf scars. Based on two- to three-year-old P. griffithii seedlings, planted in a common garden in the western Sichuan Plateau, China, the study found that the rates of basal leaf production were consistent, with leaves growing from March to April and falling off from October to December, leaving behind basal leaf scars. Thus, the age of individuals in situ could be determined by counting the leaf scars. Through this method, we determined the age structure and growth strategy of P. griffithii populations in two typical habitats in the western Sichuan Plateau. In open land habitats, the age structure of P. griffithii populations was relatively younger compared to understory habitats. In open land, P. griffithii tends to allocate more photosynthate terminal organs (leaves and fine roots) to absorbing more resources, as well as to its reproductive organs (flower stems and aggregate fruits), to expand the population. The P. griffithii population in the understory habitat is in its middle-age stage and concentrates more photosynthate in the coarse root part (e.g., the high coarse root mass fraction (FRMF)) to support the plant. Additionally, we found a significant correlation between P. griffithii plant age and various traits in open land habitats. Therefore, we conclude that plant age can be used as a good predictor of plant growth condition in open land. These results allow for predicting ecological processes, based on the ages and traits of P. griffithii plants, providing a theoretical basis to support the large-scale breeding of P. griffithii.

Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.

CONTEXT: Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. OBJECTIVE: Our study explores the effect and mechanism of STS against LUAD. MATERIALS AND METHODS: LUAD cells were treated with 100 µM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. RESULTS: STS significantly decreased the viability (40-50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. DISCUSSION AND CONCLUSIONS: STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

Within leaf nitrogen allocation regulates the photosynthetic behavior of xerophytes in response to increased soil rock fragment content.

There is limited information on how plant functional traits vary with soil rock fragment content (RFC), especially for xerophytes growing in stony soils. We examined leaf functional traits of three xerophytes (Sophora davidii; Cotinus szechuanensi; and Artemisia vestita) grown under an RFC gradient in a heavy loamy soil. Our results show that photosynthetic capacity increased linearly with RFC in S. davidii, whereas unimodal patterns were observed for the other two species. The RFC that maximized photosynthetic capacity (Asat) and photosynthetic N use efficiency (PNUE) were achieved by allocating more N to photosynthetic apparatus at the expense of cell walls. For C. szechuanensis, the increased fraction of photosynthetic N allocated to carboxylation (PC) bioenergetics (PB), and thylakoid light-harvesting components (PL) together contributed to the higher Asat and PNUE values. As for S. davidii, both PC and PB mainly contributed to higher Asat and PNUE, whereas for A. vestita only PB was the main contributor. Our results suggest that increased non-capillary porosity of high RFC soil conditions through promoting the root growth of S. davidii and C. szechuanensis ensures sufficient water and N supply for photosynthetic capacity. In shallow-rooted species A. vestita, low RFC soil maintained higher nitrate N in the topsoil, enhancing leaf photosynthetic capacity. We conclude that rock fragments promoted leaf photosynthetic capacity in the studied loamy soil system, but the promoting effect was species-specific. The results highlight the relevance of consideration of soil rock fraction in evaluation of photosynthetic behavior of xerophytes in heterogeneous rocky soils.

Photosynthetic Properties of Co-Occurring Pioneer Species on Volcanically Devastated Sites in Miyake-jima Island, Japan.

Pioneer species differing in their inherent ecological characteristics (e.g., N-fixing ability, photosynthetic pathway) can have a large impact on local ecosystems in the early stages of volcanic succession. However, it remains unclear as to how these pioneer species adapt to the extreme environment of volcanically devastated sites in terms of ecophysiological leaf traits. In this study, we compared the leaf traits (including morphological, physiological) of three co-occurring pioneer species, including a C4 non-N-fixing grass, a C3 N-fixing tree, and a C3 non-N-fixing herb from a newly created (18 years after eruption) volcanically devastated site in Miyake-jima, Japan. Our results showed that three pioneer species have different sets of leaf traits that are associated with their ecophysiological growth advantages, respectively. Miscanthus condensatus shows the highest light-saturated photosynthetic rate (Amax). The higher Amax were partially the result of higher water use efficiency (WUE) and photosynthetic N-use efficiency (PNUE). The PNUE in M. condensatus appears to be high, even for a C4 grass. Alnus sieboldiana rely on its N-fixing ability, has a higher leaf N content (Narea) that compensates for its photosynthetic machinery (Rubisco), and further ensures its photosynthetic capacity. Fallopia japonica var. hachidyoensis has a higher leaf mass per area (LMA), chlorophyll content (Chl), and maximum quantum yield of PSII (Fv/Fm), demonstrating its higher light capturing ability. These results make it possible to predict certain ecological processes that take place in the early stages of volcanic succession resulting from ecological characteristics and from some key leaf traits of pioneer species. It also provides a theoretical basis for species selection and species combination for volcanic ecological restoration.

Photosynthetic Properties of Miscanthus condensatus at Volcanically Devastated Sites on Miyake-jima Island.

How photosynthetic-related leaf traits of non-nitrogen (N)-fixing pioneer species respond to extreme habitat conditions of primary succession is still not well-elucidated, especially in volcanically N-deplete habitats. The effect of N-deplete soil on photosynthetic-related leaf traits can provide a basis for predicting how plants adjust their strategies to adapt to such habitats. To examine the responses of leaf traits to extreme conditions, we investigated Miscanthus condensatus (a non-N-fixing C4 pioneer grass) which grows on a volcanically devastated area on Miyake-jima Island, Japan, in which the volcanic ash has been deposited for 17-18 years since the 2000-year eruption. Leaf N content (Narea), light-saturated photosynthetic rate (Amax), and photosynthetic N use efficiency (PNUE) in three contrasting study sites: bare land (BL), shrub land gap (SLG), and shrub land under canopy (SLUC) were determined. Results indicated that compared to previous studies and internal comparison of Miyake Island, M. condensatus in BL was able to maintain a relatively high Amax, Narea and PNUE. The higher Amax was in part a result of the higher PNUE. This is a characteristic necessary for its successful growth in N-deplete soils. These results suggest that M. condensatus has photosynthetic-related advantages for adaptation to volcanically N-deplete habitats.

Analysis of Clinical Target Volume Delineation in Local-regional Failure of Nasopharyngeal Carcinoma after Intensity-modulated Radiotherapy.

OBJECTIVE: To analyze the pattern of local failure in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT) and find a more reasonable delineation of the clinical target volume (CTV). METHODS AND MATERIALS: A total of 212 patients with non-metastatic NPC who underwent IMRT were analyzed. Radiation therapy was run at a total dose of 66-74 Gy (2.0-2.2 Gy fractions). The follow-up of local recurrence and the recurrence-related features were analyzed for the original treatment situation. The failures were delimited as "in-field failure" if Vrecur within the 95% isodose curve (V95%) was ≥95%; "marginal failure" if V95% was less than 95% and not less than 20%; or "out-field failure" if V95% was< 20%. Kaplan-Meier method was used to calculate the survival rates. RESULTS: The median follow-up was 43.4 months. The 5-year local relapse-free survival and overall survival rates were 85.6 and 77.8%, respectively. A total of 18 patients have relapsed. The in-field failure, marginal failure, and out-field failure accounted for 83.3%, 11.1%, and 5.6%, respectively. The site of recurrence was basically in the high dose area. CONCLUSION: These findings suggested that IMRT provide a good local control for patients with NPC, and the in-field failure is the main mode. A wide range of CTV cannot prevent the local recurrence, narrowing the CTV to protect the adjacent organs should be taken into consideration.

Efficacy and Side Effects of Combined Capecitabine Plus Intensity Modulated Radiotherapy as an Effective Adjuvant Therapy for Gastric Cancers.

This study aims to evaluate the clinical outcomes and the toxicities associated with intensity modulated radiotherapy (IMRT) administered in combination with capecitabine for gastric cancer. This study was conducted between July 2009 and October 2011, and included 31 patients (23 female and eight male patients; mean age: 57 years old) with pathologically confirmed gastric cancer (pathological staging T3 or T4 or positive lymph node). All patients underwent D2 surgery and adjuvant chemoradiotherapy, followed by combined treatment with IMRT and capecitabine. All patients received follow-up examinations every 3-6 months by physical examination, magnetic resonance imaging (MRI), and assays for tumor markers. The Kaplan-Meier method was used to calculate the rates for locoregional control (LRC) and disease-free survival (DFS). Only two patients could not complete the planned treatment regimen. Patients treated with IMRT and capecitabine tolerated their treatment well, and displayed few significant side effects. The mean follow-up, disease-free survival (DFS) and survival times were 33.0, 27.5, and 32.9 months, respectively.This study confirmed that the combined administration of IMRT and capecitabine can be used as an adjuvant therapy for gastric cancer patients, with few toxic side effects.

A Novel Radiotherapy Approach for Keloids with Intrabeam.

BACKGROUND: Keloids are hard nodules or plaques formed by excessive proliferation of connective tissue. Radiotherapy, widely used in various benign and malignant skin diseases, is an effective treatment for keloids. This work evaluates Intrabeam photon radiotherapy in the management of keloids. METHODS: Fourteen patients who have undergone Intrabeam radiotherapy for a total of 15 sites of keloids were followed up. Twelve cases were first onset and the other two had recurrent diseases. Thirteen patients underwent surgical resection of keloids before radiotherapy. One relapsing patient received only 2 rounds of radiation therapy as she could not be reoperated. Radiotherapy was divided into 2 sessions on days 0 and 3 after surgery. The dose was 4 or 5 Gy each time for 3 min 14 s to 12 min 1 s. In addition, we compared our data to the recurrence of keloids in fourteen patients who had previously been exposed to electron beam using conventional accelerators. RESULTS: We analyzed the treatment for adverse reactions and recurrence. In the Intrabeam group, one patient developed superficial skin ulcers a month after treatment. No one experienced wound rupture, bleeding, infection, skin contractures, or obvious hyperpigmentation. None of the fourteen cases showed any recurrence so far after on median 22.5 months of follow-up. Five patients in the electron beam group relapsed 3 to 10 months after treatment. CONCLUSION: Here, Intrabeam photon radiotherapy was shown to be an effective treatment for keloid scars and it is therefore recommended for management of this disease.

Chaperonin-containing T­complex protein 1 subunit 8 promotes cell migration and invasion in human esophageal squamous cell carcinoma by regulating α-actin and ß-tubulin expression.

The chaperonin-containing T­complex protein 1 (CCT) has eight subunits, CCT 1-8, which are dysregulated in several types of cancer. To determine how subunit 8 (CCT8) influences the development of esophageal squamous cell carcinoma (ESCC), immunohistochemistry and western blot analysis were performed on 128 ESCC samples in the present study to measure the expression of CCT8. The prognostic value of CCT8 was analyzed using univariate and multivariate survival analyses. CCT8 knockdown in ESCC cells was performed and subsequently, the migration and invasion of ESCC cells was assessed. The results of immunohistochemistry and western blot analysis of ESCC tissue indicated that the expression of CCT8 in tumor tissues from patients with lymph node metastasis (LNM) was high whereas its expression in tissues from those without LNM was low. In addition, the overall survival rate of patients with high CCT8 expression was poor. It was demonstrated that CCT8 influenced the migration and invasion of ESCC cells by regulating α-actin and ß-tubulin. Following CCT8 knockdown, cells were treated with cisplatin; it was demonstrated that α-actin and ß-tubulin were downregulated and that cell apoptosis was enhanced. These data confirm that α-actin and ß-tubulin are regulated by CCT8, and that increased CCT8 expression is associated with poor patient prognosis and cisplatin resistance in ESCC.

Association between TAp73, p53 and VASH1 expression in lung adenocarcinoma.

TAp73 and p53 are involved in regulating tumor angiogenesis and vasohibin-1 (VASH1) is an anti-angiogenic factor. Whether TAp73 regulates angiogenesis positively or negatively is controversial. The status of P53 may determine the effect of TAp73 on angiogenesis. To the best of our knowledge it has not been previously reported whether TAp73, p53 and VASH1 are coexpressed in lung cancer. We profiled the association between TAp73 and p53 and VASH1 expression in lung adenocarcinoma (LAC) and investigated the function of TAp73 in regulating tumor angiogenesis. TAp73, p53 and VASH1 expression in 53 human LAC tissues and the adjacent normal tissues were evaluated using immunohistochemistry. The positive expression rates of p53, TAp73 and VASH1 were significantly higher (92.6, 97.7 and 67.4%, respectively) in LAC tissue compared with paraneoplastic lung tissue (7.4, 2.3 and 32.6%, respectively, P<0.01). Pearson's correlation coefficient showed a significant positive correlation between p53 and TAp73 (r=0.474, P<0.01) and TAp73α and VASH1 (r=0.367, P<0.01). The positive expression rate of p53 and VASH1 was almost significantly correlated (r=0.187, P=0.055). Similarly, p53 expression intensity had a significant positive correlation with TAp73α (r=0.517, P<0.01) and with VASH1 (r=0.277, P<0.01), as did TAp73α with VASH1 (r=0.351, P<0.01). TAp73, p53 (mutant) and VASH1 expression was significantly higher in LAC tissue compared with paraneoplastic lung tissue. The expression trends of the three proteins were significantly positively correlated with each other in LAC. These results suggest that TAp73 may suppress tumor angiogenesis in LAC.

Effect of tetramethylpyrazine combined with cisplatin on VEGF, KLF4 and ADAMTS1 in Lewis lung cancer mice.

OBJECTIVE: To further explore the function of combine use of tetramethylpyrazine (TMP) and cisplatin (DDP) in lung carcinoma. METHODS: We used the combination drug to treat Lewis lung cancer mice, investigated the expression level of vascular endothelial growth factor (VEGF), Kruppel-like factor 4 (KLF4) and A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) and to further explore the inhibitory effects and potential mechanism of TMP combined with DDP on tumor angiogenesis. RESULTS: The tumor growth was suppressed in TMP group, DDP group and TMP combined with DDP group. Furthermore, the weights and volume of tumor, the expression level of VEGF, KLF4 and ADAMTS1 were found significantly changed between experiment group and control group. These findings suggest that TMP with DDP had additional or synergistic effects to inhibit the tumor growth effectively, might be achieved through reducing the expression of angiogenesis promoting factor VEGF and increasing expression of angiogenesis inhibitors KLF4 and ADAMTS1. CONCLUSION: KLF4 and ADAMTS1 may be synergically involved in the angiogenesis in mouse Lewis lung cancer through the different signal ways.

Effect of DTPP-mediated photodynamic therapy on cell morphology, viability, cell cycle, and cytotoxicity in a murine lung adenocarcinoma cell line.

Photodynamic therapy (PDT) involves the administration and activation of photosensitizing reagents in cancer tissues to induce cytotoxicity. Here we examined the effects of 5-5- (4-N, N-diacetoxylphenyl)-10,15,20- tetraphenylporphyrin (DTPP) -mediated PDT on cell morphology, viability, cell cycle, and cytotoxicity in a murine lung adenocarcinoma cell line. LA795 murine lung adenocarcinoma cell line was used in the study, with cellular uptake of DTPP being quantified by a UV-visible spectrophotometer. The subcellular localization of DTPP was detected by confocal laser scanning microscopy, alteration of cell morphology after PDT was observed by an inverted light microscope, and late-stage apoptosis was examined by terminal dUTP nick end labeling (TUNEL) . The effects of influencing factors on cytotoxicity of PDT in LA795 cells was investigated with varying concentrations of DTPP, energy densities, power densities, and antioxidants by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Effects of PDT on cell cycle and plasma membrane integrity were studied by flow cytometry analysis. The uptake of DTPP by LA795 cells reached maximum after incubation for 24 h. Confocal laser scanning microscopy showed that DTPP was mainly in the mitochondrion, and slight localization was detected in the lysosomes. Cellular inhibitory effects increased with increased irradiation dose and DTPP concentration, while unactivated DTPP had low toxicity. Flow cytometry analysis revealed that DTPP-PDT-treated cells showed S phase arrest. Cell membrane damage initiation, repair, and irreversible damage were observed at 2, 4, and 5 h after DTPP-PDT , respectively. Together, our results demonstrated cell apoptosis, compromised viability, and cell cycle S phase arrest of LA795 in response to DTPP-PDT , while no effect on the lung cancer cells was observed with irradiation or photosensitizer treatment alone.

Prediction of extraprostatic extension in patients with clinically organ-confined prostate cancer.

INTRODUCTION: Preoperative parameters for predicting extraprostatic extension (ECE) in clinically organ-confined prostate cancer patients are not well defined. Our aim was to evaluate the roles of the biopsy Gleason score, prostate-specific antigen (PSA)-based parameters, volume, and clinical T classification in prediction of ECE. MATERIALS AND METHODS: A total of 188 patients with clinically organ-confined prostate cancer who underwent radical prostatectomy from January 1998 to December 2007 were included in the study. Age, prostate volume, preoperative total serum PSA (tPSA), free PSA, PSA density (PSAD), biopsy Gleason score, and clinical T classification were analyzed by univariate and multivariate analyses to predict ECE. RESULTS: Pathologic examination revealed 130 patients had organ-confined disease and 58 patients were positive for ECE. Multivariate logistic regression analyses showed that tPSA was an independent predictor of ECE. Gleason score ≥8 had a trend for predicting ECE. Receiver operating characteristic (ROC) curves suggested that tPSA and PSAD had a similar diagnosis performance in the whole cohort. For patients with Gleason score of 7, PSAD was found to be statistically better than tPSA for predicting ECE. CONCLUSIONS: tPSA remains one of the most important factors for predicting ECE in prostate cancer patients. PSAD may be more helpful than tPSA for predicting ECE in the patients with Gleason score of 7.

Effect of endostar combined with cisplatin on expression of VEGF and Sema3A of Lewis lung cancer rats.

OBJECTIVE: To evaluate the therapeutic effect of endostar (ED) combined with cisplatin(DDP) on model of C57BL/6 rats, and to further investigate the inhibiting mechanism of endostar from tumor angiogenesis. METHODS: Lewis lung cancer cells were inoculated in C57BL/6 mouse, then the mouse were randomized into control group (group A), ED (group B), DDP (group C) and ED/DDP (group D). They were treated according to the plan. And the expressions of VEGF and Sema3A were evaluated by immunhistochemisty. RESULTS: The weight of tumor increased in group A and B. It was decreased in group C and D. The tumor volume was increased in all the 4 groups. The VEGF expression of group D was obviously lower than the other group 3, but the Sema3A expressed of group D was significantly strengthener than the other group 3. The VEGF expression of group B and group D were obviously low especially in the 4th-8th days. Pearson correlated analysis showed that the expression VEGF and Sema3A were negatively correlated (r=-0.72, P<0.05). CONCLUSIONS: ED combined with DDP could control the tumor growth effectively, and avoid weight loss. ED could reduce VEGF expression, and enhance Sema3A expression. Tumor vessel presents transient normalization. It is easy for DDP perfusion, and to kill tumor cells.

Cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on QSG-7701 hepatocytes.

OBJECTIVE: To investigate the cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on cultured QSG-7701 cells lines. METHODS: Isoniazid, rifampicin, mixture of rifampicin and isoniazid, acetylhydrazine, hydrazine were added in cultural media of QSG-7701 cells and cultured for 48 hours. The survival rate of cells was determined by MTT method. The cultural media and cells were collected and the activity of lactate dehydrogenase was detected by chromatometry. RESULTS: Compared with control group, the survival rate decreased significantly and the lactate dehydrogenase released from cell increased significantly in cells treated with isoniazid, rifampicin, acetylhydrazine, hydrazine. Hydrazine, the metabolite of isoniazid produced significant damage on hepatocytes in low concentration. CONCLUSIONS: Rifampicin together with rifampicin and metabolites of isoniazid produce cellular toxic effects and hydrazine may be the most toxiferous metabolite.

Diagnostic value of tumor marker pro-gastrin-releasing peptide in patients with small cell lung cancer: a systematic review.

BACKGROUND: Lung cancer is one of the most common malignancies in the world and one of the leading cancers that result in death. The aim of this study was to evaluate and compare the diagnostic value of the serum tumor marker pro-gastrin-releasing peptide 31-98 (ProGRP31-98) to pathological diagnosis as reference standard in patients with suspected small cell lung cancer (SCLC). METHODS: Literature searches covering 1978 through to 2009 were performed in Pubmed, OVID, MEDLINE, EMbase, Cancerlit, China National Knowledge Infrastructure (CNKI), and CBM using the key search words; 'small cell lung cancer', 'tumor marker', 'ProGRP31-98' and 'diagnostic tests', 'ELISA', 'EIA' and 'diagnostic accuracy'. Studies were collected and data analyzed to evaluate the diagnostic value of serum ProGRP31-98 levels for the diagnosis of SCLC compared with pathology. Eligibility criteria for inclusion in the analysis were based on criteria for diagnostic research published by the Cochrane Screening and Diagnostic Tests METHODS: Group (SDTMG). The characteristics of the included articles were appraised and the data were extracted from the original articles for further statistical analysis of study heterogeneity using Review Manager 4.2 software. Based on study heterogeneity analysis, a suitable 'effect' model was selected to calculate pooled sensitivity and specificity by meta-analysis. A Summary Receiver Operating Characteristic (SROC) curve and the area under the curve (AUC) were generated and sensitivity analysis conducted. RESULTS: A total of 22 articles were entered into this meta-review, including 11 English articles with a quality at level C. In total, the studies involved 6759 subjects, of which 1470 were diagnosed with SCLC by pathology, and 5289 subjects diagnosed with non-SCLC (NSCLC). The meta-analysis showed that heterogeneity among studies was high (P = 0.00001, I(2) = 86.8%). With ELISA, the pooled sensitivity was 0.72 (0.70 to 0.75 at 95%CI) and the pooled specificity was 0.93 (0.92 to 0.94 at 95%CI); the SROC and the AUC were 0.8817. These data suggest that ProGRP31-98 has a relatively high rate of missed diagnosis (28%), but a relatively low rate of misdiagnosis (7%). CONCLUSION: From meta-analysis, we concluded that serum ProGRP31-98 is a valuable marker with a high specificity for diagnosis of SCLC with a similar diagnostic accuracy to pathology.

Evaluation of intraoperative radiotherapy for gastric carcinoma with D2 and D3 surgical resection.

AIM: To study the proper sites and doses of intraoperative radiotherapy (IORT) for gastric carcinoma and the effects of this treatment. METHODS: A total of 106 patients with stage I-IV gastric carcinoma who received D2 or D3 radical operation combined with IORT were analyzed. Sixty-seven patients with gastric cancer of the antrum and body underwent distal gastrectomy. The sites of irradiation were at the celiac artery and hepatoduodenal ligment area. Another 39 patients with carcinoma of the cardia and upper part of the gastric body and whole stomach underwent proximal gastrectomy or total gastrectomy. The sites of irradiation for this group were the upper margin of the pancreas and the regional para-aorta. The therapeutic effects (including survival and complications) of these 106 cases received operation combined with IORT (IORT group) were compared with 441 cases treated during the same time period by a radical operation alone (operation group). RESULTS: The radiation dose below 30 Gy was safe. The therapeutic method of the operation combined with IORT did not prolong the survival of patients with stage I and IV gastric cancer, but the 5-year survival rates of patients with stage II and III gastric cancers were significantly improved. The 5-year survival rates of the stages III cancer patients receiving D2 resection combined with IORT were markedly improved, while for those receiving D3 radical resection, only the postoperative 3- or 4-year survival rates were improved (P < 0.005-0.001). The 5-year survival rate for those patients was raised only by 4.7% (P > 0.05). CONCLUSION: The 5-year survival rates of patients with stages II and III gastric carcinoma who received D2 lymphadenectomy combined with IORT were improved, and there was no influence on the postoperative complications and mortality.