[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer].

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

[The effects of sequence of radiotherapy and chemotherapy on prognosis of patients with early-stage extranodal NK/T cell lymphoma (nasal type) and its individualized application].

Objective: To analyze the effects of the sequence of radiotherapy and chemotherapy on the efficacy of early-stage extranodal NK/T-cell lymphoma (nasal type, ENKTCL) patients, and to provide a quantitative evaluation method for individualized radiotherapy and chemotherapy. Methods: The Chinese Lymphoma Collaborative Group (CLCG) collected the clinical data of 2 008 patients with early-stage Ⅰ/Ⅱ ENKTCL who received radiotherapy and chemotherapy from January 2000 to early September 2019 from 21 hospitals across the country, including 1 417 males and 591 females, aged 2 to 83 (42±14) years. According to the sequence of radiotherapy and chemotherapy, patients were divided into radiotherapy-first group (388 cases) and chemotherapy-first group (1 620 cases). Survival rate was estimated using Kaplan-Meier method, and multivariate Cox proportional risk model was used to screen and identify independent prognostic factors. The prognostic prediction models of the two therapies were constructed separately, and the models were used to predict the individualized mortality risk of all patients to determine the appropriate radiotherapy and chemotherapy regimen for each patient. Results: The 5-year overall survival rate was 74.2% (95%CI: 69.6%-79.2%) in the radiotherapy-first group and 69.7% (95%CI: 67.1%-72.4%) in the chemotherapy-first group. Although the 5-year overall survival rate of patients in the radiotherapy-first group was numerically higher than that of the chemotherapy-first group, the difference was not statistically significant (χ2= 2.26, HR=0.84 (95%CI: 0.68-1.05), P=0.133). Six variables including age, gender, ECOG score, LDH, Ann Arbor staging, and PTI (primary tumor invasion) were screened out as independent prognostic factors (the chemotherapy-first group: HR were 1.01, 1.25, 2.07, 0.77, 1.34, 1.49, respectively, all P<0.05; radiotherapy-first group: HR were 1.02, 1.31, 1.66, 0.78, 1.37, 1.29, all P>0.05). The mean 5-year predicted mortality risk for all patients receiving radiotherapy-first regimen was lower than those receiving chemotherapy-first regimen (26.8% vs 30.2%, P<0.001). There were individualized differences in the predicted mortality risk of patients with different clinical characteristics who received radiotherapy-first regimen or chemotherapy-first regimen. Conclusion: Patients with stage Ⅰ/Ⅱ ENKTCL treated with radiotherapy-first regimen had a better expected prognosis than patients treated with chemotherapy-first regimen. The quantitative assessment of the differential effects of the sequence of radiotherapy and chemotherapy on the mortality risk of individual patients based on their clinical characteristics was helpful for the clinical development of the optimal radiotherapy and chemotherapy plan for each patient.

[Outcome of radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type].

Objective: To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL). Methods: A total of 557 patients from 2000-2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis. Results: The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 (P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population (P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy (P<0.001). Radiotherapy dose was an independent factor affecting LRC(P<0.05). Conclusions: Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

[Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract].

Objective: To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL). Methods: The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis. Results: Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% (P=0.281), while the PFS rates were 24.8% and 48.3%, respectively (P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival (P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival(P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions: Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

Identification of lung adenocarcinoma-specific exosome RNAs in peripheral blood by RNA-Seq analysis.

OBJECTIVE: Several plasma-derived exosome RNAs have been identified as key regulators in cancer development. They have been considered as potential biomarkers for a non-invasive "liquid biopsy" to diagnose and assess the progression of cancer. This study aimed to identify human lung adenocarcinoma-specific exosome RNAs in peripheral blood, while assessing the feasibility and efficiency of this recently developed deep-sequencing technology for transcriptome profiling. PATIENTS AND METHODS: Plasma-derived exosome RNAs were isolated from 13 lung adenocarcinoma patients, 3 patients with benign lung diseases, and 15 healthy volunteers. RNA-seq analysis of ribosomal RNA-depleted total RNA was performed. RNAs differentially expressed between lung adenocarcinoma and benign lung diseases or healthy volunteers were identified, followed by GO and KEGG pathway enrichment analyses for the identification of key exosome RNAs associated with lung adenocarcinomas. RESULTS: Significant differentially expressed RNAs, such as UDP glucuronosyltransferase family 1 member A1 (UGT1A1) and BAI1-associated protein 2 like 1 (BAIAP2L1), were identified as differentially expressed between lung adenocarcinoma patients and patients with benign lung diseases. Eight pseudogenes, including Tropomyosin 1 (Alpha) Pseudogene (LOC100129096), Prothymosin, Alpha Pseudogene 2 (PTMAP2), Cell Division Cycle 14C, Pseudogene (CDC14C), Tropomyosin 1 (Alpha) Pseudogene (LOC643634), Ferritin Heavy Chain 1 Pseudogene 2 (FTH1P2), Actin Related Protein 2/3 Complex Subunit 3 Pseudogene 3 (ARPC3P3), Ferritin Heavy Chain 1 Pseudogene 11 (FTH1P11), and Prothymosin Alpha Pseudogene 5 (PTMAP5) were identified from plasma-derived exosomes in lung adenocarcinoma patients, who were more abundant/detectable than healthy volunteers. CONCLUSIONS: Our data indicate that plasma-derived exosome RNAs, UGT1A1, and BAIAP2L1, as well as the eight isolated pseudogenes could serve as diagnostic and prognostic biomarkers for an effective non-invasive "liquid biopsy" of lung adenocarcinomas.

[Prognostic analysis of definitive radiotherapy for early esophageal carcinoma(T1-2N0M0): a multi-center retrospective study of Jing-Jin-ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group].

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.

Low pretreatment PNI correlates with worse survival in patients with stage III/IV NSCLC who received chemotherapy.

The aim of this study was to investigate the prognostic value of the prognostic nutritional index (PNI) on the long-term survival of non-small cell lung cancer (NSCLC) patients who received platinum-based chemotherapy. Data on nutritional parameters and clinicopathological characteristics [e.g., albumin, total protein, body mass index (BMI), eastern cooperative oncology group (ECOG) performance status, stage, pathology, treatment strategy] were analyzed and retrospectively correlated with overall survival (OS). The PNI was calculated based on the concentration of albumin and lymphocyte count [10 × albumin, (g/dl) + 0.005 × lymphocyte (count/mm3)]. A receiver operating characteristic curve (ROC) analysis was used to find the optimal cut-off value of PNI. Univariate and multivariate analyses were used to evaluate the prognostic value of PNI. A total of 186 patients met the inclusion criteria. The optimal cut-off value for PNI was 50.45. Compared with the parameters of the low PNI group (n=76), high PNI was significantly associated with adenocarcinoma type, stage III, better ECOG and comprehensive treatment modality. The univariate analysis demonstrated that OS was superior when PNI ≥50.45, albumin ≥35 g/l, platelet-lymphocyte ratio (PLR) ≥163 and ECOG <2, and when the patient received a comprehensive treatment modality. In the multivariate analysis, PNI, TNM stage and treatment strategy were identified as independent predictors of survival in this study. This retrospective study demonstrated that a low PNI was related to worse overall survival in patients with stage III/IV NSCLC who received platinum-based chemotherapy. These data provided a conceptual basis for further research on the clinical application of the PNI index for patients receiving chemotherapy for intermediate- and advanced-stage NSCLC.

[Association between dust exposure and the risk of hypertension of male coal miners in Henan Province].

Objective: To explore the association between dust exposure and the incidence of hypertension in male coal miners. Methods: Using the method of retrospective cohort study,a hypertension cohort of colliery in Henan Province was established in January 2006. From 2006 to 2017,all the male coal miners in a colliery who were exposed to dust were selected into the exposure group including tunneling, mining,auxiliary and combining workers, and workers from administrative logistics departments who were not exposed to dust were selected into the control group. The eligible participants should satisfy following conditions: working more than one year, with clear and complete record of occupation change, and with complete archives and reliable diagnosis of occupational health surveillance. The exclusion criteria of participants were with hypertension at the baseline of study or with heart,liver,kidney diseases and malignant tumors. A total of 12 647 participants were enrolled in this study (11 663 in the exposure group and 984 in the control group). The follow-up period was from January 2006 to December 2017,with a total follow-up of 89 259.75 person-years. Questionnaires and physical measurements were used to collect general demographic characteristics, occupational exposure history and occupational health surveillance data of all participants. The Cox proportional hazards regression model was used to estimate the association between the dust exposure and the incidence of hypertension. Results: During the follow-up period, 2 549 new-onset hypertension patients were identified with an incidence density of hypertension about 2 855.71 per 100 000 person-years. The incidence density of hypertension was 2 967.58 per 100 000 person-years in the exposure group, and 1 643.85 per 100 000 person-years in the control group. The results of multivariate Cox proportional hazards regression model showed that after the adjustment of marriage, age, smoking, alcohol drinking and body mass index,the risk of hypertension was higher in the exposure group compared with the control group (HR=1.692, 95%CI: 1.410-2.032). Further analysis showed that compared with workers from administrative logistics departments,the risk of hypertension in tunneling,mining and auxiliary working was 1.629(1.345-1.973),1.677(1.374-2.046) and 1.782(1.475-2.151),respectively. Conclusion: Dust exposure may increase the risk of hypertension in male coal miners.

miR-375 inhibits the proliferation and invasion of glioblastoma by regulating Wnt5a.

The aberrant expression of microRNA-375 (miR-375) has been proved to be associated with carcinogenesis. However, the role of miR-375 in glioblastoma (GBM) remains unknown. The aim of this study was to investigate biological functions and its molecular mechanisms of miR-375 in GBM cells. In this study, real-time PCR results showed that the level of miR-375 expression in GBM tissues and GBM cell lines (U87 and U251) was decreased. Using MTT assay, Transwell migration and invasion assay, we demonstrated that miR-375 overexpression significantly suppress cell proliferation, cell migration and cell invasion capacity in U87 and U251 cells. However, downregulation of miR-375 had reverse effects on cell proliferation, migration and invasion. Targeting association analysis, dual luciferase assay, RT-PCR and western blot analysis results confirmed that miR-375 could target the 3'UTR of Wnt5a mRNA and regulated its protein expression. Further studies also find overexpression of Wnt5a could significantly reverse miR-375-mediated proliferation, migration and invasion on U87 and U251 cells. Therefore, we concluded that miR-375 inhibited the proliferation and invasion of GBM by regulating Wnt5a and might be a possible therapeutic agent for GBM.

Fulvestrant inhibits the glycolysis of prolactinoma GH3 cells by downregulating IRE1/XBP1 signaling pathway.

OBJECTIVE: We aimed to evaluate the effects of fulvestrant on the glycolysis of prolactinoma GH3 cells, and reveal the potential regulatory mechanisms. MATERIALS AND METHODS: Prolactinoma cell line GH3 was treated with different concentrations of fulvestrant (0, 0.12, 0.25, 0.5 and 1 ng/ml) for 4 h. siRNAs XBP1s and XBP1u were constructed to treat GH3 cells. The expression levels of XBP1s, XBP1u, IRE1, PKM2 and GRP78 of GH3 cells were detected by Western blot. Meanwhile, the glycolytic activity of GH3 cells, including the glucose uptake, ATP/ADP, and lactate production were detected. RESULTS: The expression levels of XBP1s and XBP1u were significantly inhibited by fulvestrant in a dose-dependent manner. The glucose uptake, ATP/ADP and lactate production of GH3 cells were significantly inhibited by fulvestrant as well as siRNA XBP1s and XBP1u (p < 0.05). Western blot analysis suggested that the expression levels of IRE1, PKM2 and GRP78 were significantly decreased in GH3 cells treated by fulvestrant as well as siRNA XBP1s and XBP1u, compared with those in normal control (p < 0.05). CONCLUSIONS: Fulvestrant could inhibit the glycolysis of GH3 cells by downregulating IRE1/XBP1 signaling pathway, and this process was closely related with the downregulation of PKM2.

Iron homeostasis in osteoporosis and its clinical implications.

Osteoporosis has until now been considered to be a disease associated with abnormal calcium metabolism. However, an increasing number of clinical observations strongly suggest the association of iron overload with bone diseases, particularly in osteoporosis in menopausal women. The recent identification of hepcidin sheds new light into the crucial role of iron homeostasis in bone metabolism. Decreasing iron overload in cell studies as well as in animal experiments has been shown to improve bone cell metabolism and growth in vitro and in vivo. In view of the significant iron overload found in the aging population, especially in females, the therapeutic potential of lowering iron overload for the treatment of osteoporosis is suggested.

Sodium valproate inhibits MDA-MB-231 breast cancer cell migration by upregulating NM23H1 expression.

Breast cancer is a common cancer in women, with a highly variable course, from inoffensive to lethal. To find a more effective strategy for its treatment, sodium valproate has been tested as an anti-cancer drug; it is the only clinically available histone deacetylase inhibitor. However, data about the effects of sodium valproate on breast cancer are insufficient in both animals and humans; studies have yielded conflicting conclusions. In particular, little is known about the association between expression of the metastasis suppressor Nm23H1 gene and breast cancer. We hypothesized that sodium valproate regulates NM23H1 expression, and affects migration and/or invasion. We found that sodium valproate at concentrations of 0.8-3.2 mM inhibits migration and modulates Nm23H1 gene expression in a concentration-dependent manner. Confluent MDA-MB-231 cells were scratched by a micropipette tip after VPA treatment for 24 h; 24 h later, the scratch was almostly closed in the 0 mM VPA-treated cells, while the 3.2 mM VPA-treated cells migrated the slowest. The cell migration ratio exposed to 0.8, 1.6 and 3.2 mM VPA was about 66.67, 30.67 and 26.67% (P < 0.05). We also found evidence that sodium valproate upregulates NM23H1 expression, which is a clue to its anti-cancer mode of action. The NM23H1 gene expression was relative fold increased determined by Western blotting at 3.2 mM VPA. Collectively, these observations indicate that sodium valproate has potential for use in breast cancer treatment.

First Report of Broad bean wilt virus 2 in Echinacea purpurea in China.

Field-grown Echinacea purpurea plants showing necrosis, leaf roll, yellow mosaic, and mosaic symptoms in leaves were collected in June 2010 in Huairou, Beijing, China. ELISAs of extracts of four samples showed that one sample with mosaic symptoms had a positive reaction with Broad bean wilt virus 2 (BBWV-2) monoclonal antibody provided by Professor X. P. Zhou (1). The monoclonal antibody recognized the 44.7 kD coat protein subunit of BBWV-2. We used Chenopodium quinoa as an assay species to isolate the virus by sap transmissions and to maintain the virus strain. Sap from infected C. quinoa, when inoculated onto indicator plant species, induced the following symptoms: C. quinoa: local lesions in inoculated leaves, systemic chlorotic mottle in upper leaves, deformation, and apical necrosis; C. amaranticolor: chlorotic local lesions, systemic mosaic and leaf distortion; Nicotiana benthamiana: systemic mosaic; Gomphrena globosa: local purple spots in inoculated leaves and systemic infection in upper leaves; Tetragonia expansa: local lesions, but no symptoms of systemic infection; Physalis floridana: systemic mosaic. No symptoms were observed on Capsicum annuum, Datura stramonium, N. glutinosa, or N. tabacum cv. White Burley. To confirm BBWV-2 infection, total RNAs extracted from infected C. quinoa leaves were reverse transcripted to cDNA using oligo-dT primer (T17V). The primer pair Fab5'R1F (5'-AAATATTAAAACAAACAGCTTTCGTT-3') and Fab5'R1R (5'-TTCAAAGCTCGTGCCATNTYATTKGC-3') for specific detection of the Fabavirus genus (2) was used for PCR analysis. The amplified fragment is between the 5'-terminal non-translatable region (NTR) and the beginning of the coding region of RNA1. Amplicons of approximately the expected size (~391 bp) were produced from the virus-infected C. quinoa and a BBWV-2 positive control (ATCC PV131, PV0537). Amplicons of approximately the expected size (~350 bp) were produced from the BBWV-1 positive control (ATCC PV132). However, no such amplicons were observed from healthy C. quinoa plants and water control. The 391-bp amplicons of RNA1 obtained from the infected C. quinoa were cloned and sequenced. Comparison with sequences of other BBWV-2 isolates showed that the isolate we obtained (No. JX070674) had approximately 99% nt identity (98% amino acid identity) with Chinese BBWV-2 isolate BC (No. FJ485686.1) (3). As an ornamental and medicinal plant, E. purpurea is widely cultivated in northern China. Up until now, Tomato ring spot virus, Tobacco rattle virus, Cucumber mosaic virus, and Tomato spotted wilt virus have been detected or isolated from E. purpurea in the world (4). To our knowledge, this is the first report of BBWV-2 infecting E. purpurea in China. BBWV-2-infected E. purpurea may have less secondary metabolites, which could influence the quality and therapeutic efficacy of this herbal medicine. References: (1) L. Qing et al. Acta Microbiologica Sinica 40:166, 2000. (2) R. M. Ferrer et al. J. Virol. Methods 144:156, 2007. (3) C. Sui et al. Plant Dis. 93:844, 2009. (4) B. Dikova. Bulgarian J. Agric. Sci. 17:306, 2011.

Occurrence of Cucumber green mottle mosaic virus on Cucurbitaceous Plants in China.

Cucumber green mottle mosaic virus (CGMMV) was first discovered in 2003 in China (2) and developed an epidemic during 2005 (1). To know the occurrence scale and damage level of CGMMV, a survey was carried out in the main areas of cucurbitaceous plant production and seed trading in 2006 and 2007 in Mainland China. Samples of 739 plants of 16 types (seed samples from Cucurbita moschata, Cucumis melo, Lagenaria siceraria, Cucumis sativus, Momordica charantia, L. siceraria var. clavata, and C. pepo, leaf samples from C. moschata, Cucumis melo, L. siceraria, Cucumis sativus, and M. charantia, fruit samples from C. moschata, Citrullus lanatus, and L. siceraria, and seedling samples from Citrullus lanatus) were collected from 13 regions and analyzed by a double antibody sandwich (DAS)-ELISA. CGMMV was detected in Citrullus lanatus, L. siceraria, Cucumis melo, and C. moschata from six regions in 2006. Citrullus vulgaris, Cucumis melo, and C. moschata were infected most frequently; in 76, 60, and 30 of the leaf samples, respectively. CGMMV was tested positive in the samples of 8 seedlings, 23 seeds, and 1 fruit. In contrast, all samples tested negative in 2007. To confirm CGMMV identification, ELISA-positive samples were detected by reverse transcription-PCR assay using virus-specific primers that amplified a 524-bp fragment in the coat protein coding region. The nucleotide sequence of the PCR product (GenBank Accession No. DQ997778) isolated form L. siceraria in Liaoning Province (LHP) showed 100% identity with the Japanese watermelon strain (Japan W) and 91% identity with the Greece GR5 strain. On the basis of the symptoms of indicator plants (chlorotic spot and systemic mosaic were observed in L. siceraria, Chenopodium amaranticolor, and Cucumis sativus; no infection was observed in Datura stramonium, Nicotiana tabacum, and Chenopodium quinoa) and coat protein nucleotide sequence comparisons, the two CGMMV isolates of Wcn (1) and LHP from China should be grouped into the watermelon strain. The results showed that the government should establish effective quarantine strategy and the growers take proper planting measures to avoid further spreading of this virus. References: (1) H. Y. Chen et al. Acta Phytopathol. Sin. 36:306, 2006. (2) B. X. Qin et al. Plant Quarantine. 19:4, 2005.

[Lipid peroxidation injury to red blood cells during extracorporeal circulation: mechanism and protection].

Twelve dogs were subjected to cardiopulmonary bypass with membrane oxygenator for 120 minutes. The effect of lipid peroxide injury on red blood cells was studied by measurement of plasma and erythrocyte membrane lipid peroxide, deformabioity of erythrocyte, plasma free hemoglobin, superoxide dismutase, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase of erythrocytes. The effect of vitamin E on red blood cells was also investigated. The findings indicated that vitamin E might protect red blood cells from lipid peroxide injury during extracorporeal circulation. The mechanism of damage effect of lipid peroxide and the protective effect of vitamin E on red blood cells were briefly discussed.

Seasonal variations in plasma progesterone concentrations in cyclic Taiwan yellow cattle (Bos indicus)

Plasma concentrations of progesterone were measured by radioimmunoassay in plasma samples obtained from 11 mature cyclic cows of native Taiwan Yellow cattle during the warm (March-April) and cool (November-December) seasons. Progesterone levels began to increase after Day 4 (Day 0 = the day of estrus) and reached maximum values on Day 10 and Day 14 for cool and warm seasons, respectively. Progesterone concentrations in plasma during the estrous cycle were significantly higher (p < 0.001) in the cool season (2.66 +/- 0.19 ng/ml) than in the warm season (1.98 +/- 0.15 ng/ml).

Comparisons of diet and biochemical characteristics of stool and urine between Chinese populations with low and high colorectal cancer rates.

In an investigation of the roles of diet and stool biochemistry in human colorectal carcinogenesis, 24-hour food, urine, and stool samples were collected from randomly selected participants from two populations with a fourfold difference in colorectal cancer risk: Chinese in Sha Giao, People's Republic of China (low risk), and Chinese-Americans of similar ages in San Francisco County, Calif, in the United States (high risk). The findings supported the hypotheses that colorectal cancer risk is increased by the consumption of high-fat, high-protein, and low-carbohydrate diets and is associated with high levels of cholesterol in stool as well as increased daily outputs of 3-methyl-histidine and malonaldehyde in urine. However, risk does not increase with low stool bulk and low total stool fibers.