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Sample records for 7-d triple therapy

  1. One-year follow-up study of Helicobacter pylori eradication rate with 13C-urea breath test after 3-d and 7-d rabeprazole-based triple therapy

    PubMed Central

    Wang, Hwang-Huei; Chou, Jen-Wei; Liao, Kuan-Fu; Lin, Zong-Yi; Lai, Hsueh-Chou; Hsu, Chang-Hu; Chen, Chih-Bin

    2005-01-01

    AIM: To investigate the long-term role of a 3-d rabeprazole-based triple therapy in patients with Helicobacter pylori(H pylori)-infected active peptic ulcers. METHODS: We prospectively studied 115 consecutive patients with H pylori-infected active peptic ulcers. H pylori infection was confirmed if any two of H pylori DNA, histology, and rapid urease test were positive. Patients were assigned to either an open-labeled 3-d course of oral amoxicillin 1000 mg b.i.d., clarithromycin 500 mg b.i.d., and rabeprazole 20 mg b.i.d., or 7-d course of oral amoxicillin 1000 mg b.i.d., clarithromycin 500 mg b.i.d., and rabeprazole 20 mg b.i.d. Subsequently, all patients received oral rabeprazole 20 mg once daily until the 8th wk. Three months after therapy, all patients were followed-up endoscopically for the peptic ulcer, H pylori DNA, histology, and rapid urease test. One year after therapy, H pylori infection was tested using the 13C-urea breath test. RESULTS: The ulcer healing rates 3 mo after therapy were 81.0% vs 75.4% for the 3-d and 7-d groups [intention-to-treat (ITT) analysis, P = 0.47] respectively, and 90.4% vs 89.6% for the 3-d and 7-d groups [per-protocol (PP) analysis, P = 0.89] respectively. The eradication rates 3 mo after therapy were 75.9% vs 73.7% for the 3-d and 7-d groups (ITT, P = 0.79) respectively, and 84.6% vs 87.5% for the 3-d and 7-d groups (PP, P = 0.68) respectively. One year after therapy, seventy-five patients returned to receive the 13C-urea breath test, and the eradication rates were 78.4% vs 81.6% in 3-d and 7-d groups (PP, P = 0.73) respectively. CONCLUSION: Our study showed the eradication rates against H pylori infection 3 and 12 mo after triple therapy were not different between the 3-d and 7-d rabeprazole-based groups. Therefore, the 3-d rabeprazole-based triple therapy may be an alternative treatment for peptic ulcers with H pylori infection. PMID:15786549

  2. Efficacy of 14-d vs 7-d moxifloxacin-based triple regimens for second-line Helicobacter pylori eradication

    PubMed Central

    Hwang, Jae Jin; Lee, Dong Ho; Lee, Ae-Ra; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

    2015-01-01

    AIM: To evaluate the efficacy of the 14-d moxifloxacin-based triple therapy for the second-line eradication of Helicobacter pylori (H. pylori) infection. METHODS: Between 2011 and 2013, we conducted a retrospective review of the medical records of 160 patients who had experienced failure of their first-line proton pump inhibitor-based eradication therapy and subsequently received the moxifloxacin-based triple therapy as a second-line eradication treatment regimen. The patients who were treated with the moxifloxacin-based triple therapy (oral 20 mg rabeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 400 mg moxifloxacin q.d.) for 7 d were assigned to the RAM-7 group (n = 79) while those who took them for 14 days were assigned to RAM-14 group (n = 81). The eradication rates for both groups were determined by intention-to-treat (ITT) and per-protocol (PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as the documentation of a negative 13C-urea breath test 4 wk after the end of the eradication treatment. RESULTS: The overall ITT eradication rate was 76.2% (122/160). The final ITT eradication rates were 70.8% (56/79; 95%CI: 63.3%-77.1%) in the RAM-7 group and 81.4% (66/81; 95%CI: 74.6%-88.3%) in the RAM-14 group (P = 0.034). The overall PP eradication rate was 84.1% (122/145), and the final PP eradication rates were 77.7% (56/72; 95%CI: 70.2%-85.3%) in the RAM-7 group and 90.4% (66/73; 95%CI: 82.8%-98.1%) in the RAM-14 group (P = 0.017). The H. pylori-eradication rates in the RAM-14 group were significantly higher compared with that of the RAM-7 group according to both the ITT (P = 0.034) and the PP analyses (P = 0.017). Both groups exhibited good treatment compliance (RAM-7/RAM-14 group: 100%/100%). The adverse event rates were 19.4% (14/72) and 20.5% (15/73) in the

  3. Triple therapy for the management of COPD: a review.

    PubMed

    Gaebel, Kathryn; McIvor, R Andrew; Xie, Feng; Blackhouse, Gord; Robertson, Diana; Assasi, Nazila; Hernandez, Paul; Goeree, Ron

    2011-06-01

    Triple therapy for COPD consists of a long-acting anti-cholinergic bronchodilator, a long-acting beta-agonist bronchodilator, and an inhaled corticosteroid. Guidelines from the Canadian Thoracic Society advocate triple therapy for some patients with moderate-to-severe COPD. The objective of this review was to evaluate the evidence based clinical efficacy of triple therapy compared to dual bronchodilator therapy (long-acting anti-cholinergic bronchodilator + beta-agonist bronchodilator) or long-acting anti-cholinergic bronchodilator monotherapy for managing COPD. A systematic literature search was conducted to identify relevant clinical evaluations of triple therapy in the management of moderate to severe COPD. Databases searched included: Medline; EMBASE; CINAHL and PubMed (non-Medline records only). Of 2,314 publications, 4 articles evaluated triple therapy for the management of COPD. Hospitalization rates for COPD exacerbations, reported in 2 trials, were significantly reduced with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy, with reported relative risks of 0.53 (95% CI: 0.33, 0.86, p = 0.01) and 0.35 (95% CI: 0.16-0.78, p = 0.011). Exacerbation data is inconsistent between the two trials reporting this outcome. Lung function, dyspnea and quality of life data show statistical significant changes with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy but the changes do not reach clinical importance. Triple therapy does decrease the number of hospitalizations for severe/acute COPD exacerbations compared with long-acting anti-cholinergic bronchodilator monotherapy. There is insufficient evidence to determine if triple therapy is superior to dual bronchodilator therapy. PMID:21513437

  4. Evaluation of Helicobacter pylori eradication by triple therapy plus Lactobacillus acidophilus compared to triple therapy alone.

    PubMed

    Medeiros, J A da Silva; Gonçalves, T M F O; Boyanova, L; Pereira, M I de Correia; de Carvalho, J N da Silva Paiva; Pereira, A M de Sousa; Cabrita, A M Silvério

    2011-04-01

    The purpose of this study was to evaluate the influence of adding Lactobacillus acidophilus to a triple regimen for Helicobacter pylori eradication in untreated patients with peptic ulcers or ulcer-scars. This was a pre-randomized, single-blind, interventional, treatment-efficacy study with active controls and parallel-assignment, set in Coimbra, Portugal, on 62 consecutive H. pylori-positive untreated adults with peptic ulcers or ulcer-scars, diagnosed by gastroduodenoscopy, with pre-treatment direct Gram-staining and culture of gastric biopsies. The first 31 patients received esomeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg (EAC), all b.i.d., for 8 days. The remaining 31 added L. acidophilus, 5 × 10(9) organisms per capsule, 3 + 2 i.d. for 8 days (EACL). The main outcome measure was (13)C urea breath test (UBT), ≥6 weeks after completion of therapy. Successful eradication (UBT-negativity after treatment), was similar in both groups (EAC = 80.6%; EACL = 83.9%, p = 0.740) by both intention-to-treat and per-protocol analysis. The non-eradicated strains were susceptible in vitro to both antibiotics. Adding L. acidophilus to EAC triple therapy did not increase H. pylori eradication rates. Considering the cost and the burden of ingesting five extra capsules daily, supplementing the EAC therapy with L. acidophilus, at this dose, shows no benefit. Further studies with different dosages and duration of treatment, and other probiotics or probiotic combinations are required to improve eradication. PMID:21207091

  5. Seven-day triple therapy is a better choice for Helicobacter pylori eradication in regions with low antibiotic resistance

    PubMed Central

    Tong, Yue-Feng; Lv, Jun; Ying, Li-Yuan; Xu, Fang; Qin, Bo; Chen, Ming-Tong; Meng, Fei; Tu, Miao-Ying; Yang, Ning-Min; Li, You-Ming; Zhang, Jian-Zhong

    2015-01-01

    AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance. METHODS: A total of 1106 Helicobacter pylori (H. pylori)-positive patients were divided into three groups, each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the 13C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ2 tests. RESULTS: The eradication rates in groups A, B and C were 90.71% (332/366), 90.46% (313/346) and 90.87% (189/208), respectively (P = 0.986). The resistance rates were 8.91% for clarithromycin, 14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin- and levofloxacin-resistant patients (P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients (P = 0.034). However, levofloxacin resistance had no obvious influence on the eradication rate. Furthermore, three main antibiotics (clarithromycin, levofloxacin and amoxicillin) had lower DID (defined daily dose per 1000 inhabitants per day) in this city. CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance, a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions. PMID:26672777

  6. A Randomized Controlled Study Comparing Reverse Hybrid Therapy and Standard Triple Therapy for Helicobacter pylori Infection.

    PubMed

    Hsu, Ping-I; Kao, Sung-Shuo; Wu, Deng-Chyang; Chen, Wen-Chi; Peng, Nan-Jing; Yu, Hsien-Chung; Wang, Huay-Min; Lai, Kwok-Hung; Cheng, Jin-Shiung; Chen, Angela; Chuah, Seng-Kee; Tsay, Feng-Woei

    2015-12-01

    Reverse hybrid therapy is an 1-step 2-phase treatment for Helicobacter pylori (H. pylori) infection with less cost than standard triple therapy. We conducted a randomized, controlled study to compare the efficacies of standard triple therapy and reverse hybrid therapy in the treatment of H. pylori infection. From October 2012 to March 2015, consecutive H. pylori-infected subjects were randomly allocated to receive either a reverse hybrid therapy (pantoprazole plus amoxicillin for 12 days and clarithromycin plus metronidazole for the initial 7 days) or a standard triple therapy (pantoprazole plus amoxicillin and clarithromycin for 12 days). H. pylori status was assessed 6 weeks after treatment. Additionally, antibiotic resistances and host CYP2C19 genotypes were examined and analyzed. A total of 440 H. pylori-infected patients were randomly assigned to receive either a reverse hybrid (n = 220) or a standard triple therapy (n = 220). The reverse hybrid group had a higher eradication rate than standard triple group either by intention-to-treat (93.6% vs. 86.8%; P = 0.016) or per-protocol analysis (95.7% vs. 88.3%; P = 0.005). The 2 patient groups exhibited similar frequencies of overall adverse events (14.1% vs. 9.5%) and drug compliance (96.8% vs. 98.6%). Clarithromycin resistance was an independent risk factor predicting eradication failure in standard triple group (P < 0.001), but not in reverse hybrid group. CYP2C19 genotypes did not affect the eradication rates in both groups. Reverse hybrid therapy can be considered for first-line treatment of H. pylori infection since the new therapy achieves a higher eradication rate than standard triple therapy with similar tolerability and less pharmaceutical cost. PMID:26632893

  7. A Randomized Controlled Study Comparing Reverse Hybrid Therapy and Standard Triple Therapy for Helicobacter pylori Infection

    PubMed Central

    Hsu, Ping-I; Kao, Sung-Shuo; Wu, Deng-Chyang; Chen, Wen-Chi; Peng, Nan-Jing; Yu, Hsien-Chung; Wang, Huay-Min; Lai, Kwok-Hung; Cheng, Jin-Shiung; Chen, Angela; Chuah, Seng-Kee; Tsay, Feng-Woei

    2015-01-01

    Abstract Reverse hybrid therapy is an 1-step 2-phase treatment for Helicobacter pylori (H. pylori) infection with less cost than standard triple therapy. We conducted a randomized, controlled study to compare the efficacies of standard triple therapy and reverse hybrid therapy in the treatment of H. pylori infection. From October 2012 to March 2015, consecutive H. pylori-infected subjects were randomly allocated to receive either a reverse hybrid therapy (pantoprazole plus amoxicillin for 12 days and clarithromycin plus metronidazole for the initial 7 days) or a standard triple therapy (pantoprazole plus amoxicillin and clarithromycin for 12 days). H. pylori status was assessed 6 weeks after treatment. Additionally, antibiotic resistances and host CYP2C19 genotypes were examined and analyzed. A total of 440 H. pylori-infected patients were randomly assigned to receive either a reverse hybrid (n = 220) or a standard triple therapy (n = 220). The reverse hybrid group had a higher eradication rate than standard triple group either by intention-to-treat (93.6% vs. 86.8%; P = 0.016) or per-protocol analysis (95.7% vs. 88.3%; P = 0.005). The 2 patient groups exhibited similar frequencies of overall adverse events (14.1% vs. 9.5%) and drug compliance (96.8% vs. 98.6%). Clarithromycin resistance was an independent risk factor predicting eradication failure in standard triple group (P < 0.001), but not in reverse hybrid group. CYP2C19 genotypes did not affect the eradication rates in both groups. Reverse hybrid therapy can be considered for first-line treatment of H. pylori infection since the new therapy achieves a higher eradication rate than standard triple therapy with similar tolerability and less pharmaceutical cost. PMID:26632893

  8. Triple nucleoside reverse transcriptase inhibitor therapy in children.

    PubMed

    Handforth, Jennifer; Sharland, Mike

    2004-01-01

    Much of the success attributed to HIV therapy in the last few years has resulted from improved ways of using existing drugs in combination therapy regimens. The availability of new, more potent drugs such as protease inhibitors and more accurate viral load tests to aid decisions to start or change treatment has also contributed to the success. Published recommendations for pediatric HIV therapy, generated by a panel of experts and specialists, are readily available and regularly updated. Preferred regimens of 'potent' therapy (referred to as highly active antiretroviral therapy, or HAART) currently consist of two nucleoside reverse transcriptase inhibitors (NRTIs) combined with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor. More intense four-drug regimens using an NNRTI or a second protease inhibitor as a fourth drug are being evaluated. Problems with HAART include: unpalatable drug formulations and adverse effects, coupled with lack of data on the pharmacokinetics, efficacy, and safety of various drug combinations. Adherence is a major factor influencing the efficacy and outcome of antiretroviral therapy. Many children cannot adhere to complex multidrug regimens, which cause virologic failure, despite excellent CD4+ cell count responses. This means a rapid progression through the limited number of treatment regimens available. Simpler regimens such as those containing three NRTIs have been proposed as a method of treatment that will allow suppression of the virus, yet circumvent many of the problems previously mentioned. An additional benefit would be the preservation of antiretroviral drugs from other classes for future treatment options if required. The major advantages of triple NRTI regimens are the simplicity of the regimen, good tolerability, few drug-drug interactions, and infrequent adverse effects coupled with a low pill burden. However, abacavir hypersensitivity remains a major problem. Up to 3% of patients may

  9. Targeted Therapies in Triple-Negative Breast Cancer

    PubMed Central

    Marmé, Frederik; Schneeweiss, Andreas

    2015-01-01

    Summary Triple-negative breast cancer (TNBC) is a heterogeneous disease comprised of several biologically distinct subtypes. However, treatment is currently mainly relying on chemotherapy as there are no targeted therapies specifically approved for TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. New targeted approaches are, therefore, urgently needed. Currently, bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A antibody, is the only targeted agent with an approval for the therapy of metastatic breast cancer, but does not provide a specific benefit in the TNBC subtype. This review discusses the current clinical developments in targeted approaches for TNBC, including anti-angiogenic therapies, epidermal growth factor receptor (EGFR)-targeted therapies, poly(ADP-ribose) polymerase (PARP) inhibitors and platinum salts, as well as novel strategies using immune-checkpoint inhibitors, which have recently demonstrated first promising results. Strategies focusing on specific subtypes of TNBC like anti-androgenic therapies for the luminal androgen receptor subtype (LAR) and others are also discussed. PMID:26557820

  10. Moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori infection

    PubMed Central

    Lim, Ji Hyun; Lee, Dong Ho; Lee, Seong Tae; Kim, Nayoung; Park, Young Soo; Shin, Cheol Min; Song, In Sung

    2015-01-01

    AIM: To assess the efficacy of moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori (H. pylori) eradication. METHODS: Between January 2010 and December 2012, we screened individuals who were prescribed non-bismuth quadruple therapy for H. pylori eradication. Among them, a total of 98 patients who failed non-bismuth quadruple therapy received 1-wk or 2-wk moxifloxacin-containing triple therapy (400 mg moxifloxacin once daily, and 20 mg of rabeprazole and 1 g of amoxicillin twice daily). H. pylori status was evaluated using the 13C-urea breath test 4 wk later, after treatment completion. The eradication rates were determined by intention-to-treat and per-protocol analyses. RESULTS: In total, 60 and 38 patients received 1-wk and 2-wk moxifloxacin-containing triple therapy, respectively. The intention-to-treat and per-protocol eradication rates were 56.7% (95%CI: 45.0-70.0) and 59.6% (95%CI: 46.6-71.7) in the 1-wk group and 76.3% (95%CI: 63.2-89.5) and 80.6% (95%CI: 66.7-91.9) in the 2-wk group (P = 0.048 and 0.036, respectively). All groups had good compliance (95% vs 94.9%). Neither group showed serious adverse events, and the proportions of patients experiencing mild side effects were not significantly different (21.1% vs 13.9%). Clinical factors such as age, sex, alcohol and smoking habits, comorbidities, and presence of gastric or duodenal ulcer did not influence the eradication therapy efficacy. The efficacy of second-line eradication therapy did not differ significantly according to the first-line regimen. CONCLUSION: Two-week moxifloxacin-containing triple therapy showed better efficacy than a 1-wk regimen after non-bismuth quadruple therapy failure. PMID:26673999

  11. Evaluation of Helicobacter Pylori eradication in pediatric patients by triple therapy plus lactoferrin and probiotics compared to triple therapy alone

    PubMed Central

    2012-01-01

    Background To evaluate whether the addition of a probiotic could improve Helicobacter pylori (H.P.) eradication rates and reduce the side effects of treatment in children. Methods Between July 2008 and July 2011 all patients with a clinical, laboratory and endoscopic diagnosis of H.P. positive gastritis referred to our Unit were included in the study. Patients suffering from allergy to any of drugs used in the study, with previous attempts to eradicate H.P. and those who received antibiotics, PPIs or probiotics within 4 weeks were excluded from the present study. Patients were randomized into two therapy regimens (group A and B): both groups received standard triple treatment (omeprazole, amoxicillin and clarithromycin) while only group B patients were also given a probiotic (Probinul - Cadigroup). Patients compliance was evaluated at the end of the treatment. Successful eradication was defined as a negative 13 C-urea breath test (C13-ubt) result four weeks after therapy discontinuation. Results A total of 68 histopathologically proven H.P.-infection children (32 male and 36 females) were included in the study. All of the patients in both groups used more than 90% of the therapies and no patients were lost at follow up. All side effects were selflimiting and disappeared once the therapy was terminated. Epigastric pain was observed in 6 (17.6%) group A vs 2 (5.8%) group B patients (P<0.05), nausea in 3 (8.8%) group A vs 1 (2.9%) group B patients (P<0.05); vomiting and diarrhea were observed in 2(5.8%) and 8 (23.5%) group A patients, respectively and never in group B (P<0.05). There was no significant difference between the two groups in terms of constipation (5.8% in group A and B). Four weeks after the completion of therapy, 56/68 patients (82.3%) tested negative for H.P. on C13-ubt. H.P. was eradicated in 26 patients (76.4%) in group A and in 30 patients (88.2%) in group B. There was no significantly difference in the rate of H.P. eradication between group A and

  12. Outcome of Inhaler Withdrawal in Patients Receiving Triple Therapy for COPD

    PubMed Central

    Kim, Sae Ahm; Lee, Ji-Hyun; Kim, Eun-Kyung; Kim, Tae-Hyung; Kim, Woo Jin; Lee, Jin Hwa; Yoon, Ho Il; Baek, Seunghee; Lee, Jae Seung; Oh, Yeon-Mok

    2016-01-01

    Background The purpose of this study was to document outcomes following withdrawal of a single inhaler (step-down) in chronic obstructive pulmonary disease (COPD) patients on triple therapy (long-acting muscarinic antagonist and a combination of long-acting β2-agonists and inhaled corticosteroid), which a common treatment strategy in clinical practice. Methods Through a retrospective observational study, COPD patients receiving triple therapy over 2 years (triple group; n=109) were compared with those who had undergone triple therapy for at least 1 year and subsequently, over 9 months, initiated inhaler withdrawal (step-down group, n=39). The index time was defined as the time of withdrawal in the stepdown group and as 1 year after the start of triple therapy in the triple group. Results Lung function at the index time was superior and the previous exacerbation frequency was lower in the stepdown group than in the triple group. Step-down resulted in aggravating disease symptoms, a reduced overall quality of life, decreasing exercise performance, and accelerated forced expiratory volume in 1 second (FEV1) decline (54.7±15.7 mL/yr vs. 10.7±7.1 mL/yr, p=0.007), but there was no observed increase in the frequency of exacerbations. Conclusion Withdrawal of a single inhaler during triple therapy in COPD patients should be conducted with caution as it may impair the exercise capacity and quality of life while accelerating FEV1 decline. PMID:26770231

  13. First-line eradication of Helicobacter pylori: are the standard triple therapies obsolete? A different perspective.

    PubMed

    Buzás, György-Miklós

    2010-08-21

    Studies concerning the eradication of Helicobacter pylori have resulted in a proliferation of meta-analyses. To date, there are 303 meta-analyses cited in PubMed, 113 dealing with the therapy of the infection. A chronological analysis of the results of meta-analyses performed between 1998 and 2010 shows that first-line standard triple therapies achieved eradication rates on an intention-to-treat basis of around 80%; prolonging treatment to 14, but not 10 d should improve the results. The proton pump inhibitors have a similar efficiency, and giving a double dose is more efficient than the standard doses of these drugs. Triple and quadruple therapies proved to be equivalent. Based on meta-analytical data, the decrease in efficiency over time cannot be substantiated: eradication rates < 80% followed from the introduction of triple therapies. As alternatives, ranitidine bismuth citrate-, levofloxacin- or furazolidone-based therapies were shown to obtain the same eradication rates as standard triple regimens. Sequential therapies and quadruple non-bismuth-based therapies were superior to standard triple therapies but their use is limited to certain countries. In the author's opinion, and from a meta-analytical viewpoint, standard triple therapies cannot yet be considered obsolete. Furthermore, non-inferiority trials are proposed for the future, including assessment of local contemporary antimicrobial resistance profiles and the CagA and CYP2C19 status of the enrolled patients. PMID:20712046

  14. Novel therapy for locally advanced triple-negative breast cancer

    PubMed Central

    YAMADA, ATSUKO; OSADA, SHINJI; TANAHASHI, TOSHIYUKI; MATSUI, SATOSHI; SASAKI, YOSHIYUKI; TANAKA, YOSHIHIRO; OKUMURA, NAOKI; MATSUHASHI, NOBUHISA; TAKAHASHI, TAKAO; YAMAGUCHI, KAZUYA; YOSHIDA, KAZUHIRO

    2015-01-01

    To evaluate a novel therapy for triple-negative breast cancer (TNBC), the biological responses to vitamin K3 (VK3) should be considered with the understanding of the features of breast cancer. In human breast cancer cell lines, the effects of VK3 on cell growth inhibition and the cellular signaling pathway were determined by MTT assay and western blotting. In the in vivo study, a subcutaneous tumor model of breast cancer was created, VK3 was injected into the subcutaneous tumors, and tumor size was measured. The IC50 of VK3 for breast cancer cells was calculated to be 11.3–25.1 μM. VK3 induced phosphorylation of whole tyrosine and epidermal growth factor receptor. VK3 mediated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) for 30 min. ERK but not JNK phosphorylation was maintained for at least 6 h. In contrast, another antioxidant agent, catalase, showed no effect on either ERK phosphorylation or growth inhibition. On built-up tumors under the skin of mice, local treatment with VK3 was effective in a time- and dose-dependent manner, and the experiments for total tumor volume also showed a dose-dependent effect of VK3. The expression of phosphorylated ERK was clearly detected at 10.9 times the control in tumor tissue, whereas ethanol itself showed no effect. In conclusion, ERK plays a critical role in VK3-induced growth inhibition, and it will be the focus of next steps in the development of molecular therapy for TNBC. PMID:26252842

  15. Does emerging Clarithromycin resistance signal an obituary to empirical standard triple therapy for Helicobacter pylori infection?

    PubMed

    John, Anil; Al Kaabi, Saad; Doiphode, Sanjay; Chandra, Prem; Sharma, Manik; Babu, Ragesh; Yacoub, Rafie; Derbala, Moutaz

    2015-09-01

    Despite 30 years of its discovery, the ideal therapeutic regimen against Helicobacter pylori is still evasive. Clarithromycin-based standard triple therapy which has been considered the first line empirical therapy has been failing in many parts of the world, due to rising resistance against Clarithromycin, forcing the use of alternate regimens. In this context, we studied the local antibiotic resistance patterns against H. pylori and its impact on standard triple therapy in our region. All patients undergoing diagnostic upper endoscopy during the study period and detected to be positive for rapid urease test (RUT) underwent cultures of gastric mucosal specimens and had their antibiotic resistance patterns mapped out. Standard triple therapy was administered to those tested positive for H. pylori by RUT and eradication rates checked by urea breath test 4 weeks after the completion of treatment. Eradication rates with Clarithromycin-based standard triple therapy were suboptimal with a success of only (71.28%). H. pylori culture and antibiotic susceptibility studies showed high resistance to Clarithromycin (21.2%), Metronidazole (78.1%), and Levofloxacin (15%). However, the resistance to Amoxicillin (2.9%), Tetracycline (0%), and Rifabutin (4.5%) were low. Standard triple therapy is failing in our region due to high Clarithromycin resistance. We need to abandon empirical and blind triple therapy without post-treatment testing and devise alternate effective treatment strategies against H. pylori based on the local resistance patterns observed. PMID:26541342

  16. Do Probiotics Improve Eradication Response to Helicobacter Pylori on Standard Triple or Sequential Therapy?

    PubMed Central

    Dajani, Asad I.; Hammour, Adnan M. Abu; Yang, Ding H.; Chung, Peter C.; Nounou, Mohammed A.; Yuan, KaiTao Y.; Zakaria, Mohammed A.; Schi, Hanping S.

    2013-01-01

    Background: The standard triple therapy for the eradication of Helicobacter pylori consists of a combination of a proton pump inhibitor at a standard dose together with two antibiotics (amoxicillin 1000 mg plus either clarithromycin 500 mg or metronidazole 400 mg) all given twice daily for a period of 7-14 days. Recent reports have shown a dramatic decline in the rate of H. pylori eradication utilizing standard triple therapy from 95% down to 70-80%. Aims: Our study was designed to evaluate the effect of adding a probiotic as an adjuvant to common regimens used for H. pylori eradication. Materials and Methods: An open label randomized observational clinical study was designed to test three different regimens of H. pylori eradication treatment: Standard triple therapy with a concomitant probiotic added at the same time (n = 100), starting the probiotic for 2 weeks before initiating standard triple therapy along with the probiotic (n = 95), and the third regimen consists of the probiotic given concomitantly to sequential treatment (n = 76). The three arms were compared to a control group of patients treated with the traditional standard triple therapy (n = 106). Results: The eradication rate for the traditional standard therapy was 68.9%, and adding the probiotic “Bifidus infantis” to triple therapy, led to a successful rate of eradication of 83% (P < 0.001). Pre-treatment with 2 weeks of B. infantis before adding it to standard triple therapy increased the success rate of eradication to 90.5%. Similar improvement in eradication rate was noted when B. infantis was added as an adjuvant to the sequential therapy leading to an eradication rate of 90.8%. Conclusion: Adding B. infantis as an adjuvant to several therapeutic regimens commonly used for the eradication of H. pylori infection significantly improves the cure rates. PMID:23680708

  17. Triple therapy in type 2 diabetes; a systematic review and network meta-analysis

    PubMed Central

    Bettington, Emilie K.; Gunton, Jenny E.; Turkstra, Erika

    2015-01-01

    Aims. The purpose was to evaluate the evidence for triple therapy regimen using medicines available in Australia for type 2 diabetes. Methods. A systematic literature review was performed to update the relevant evidence from 2002 to 2014 on triple therapy for type 2 diabetes. A multiple-treatments network meta-analysis was undertaken to summarise the comparative efficacy and harms of different triple therapies. Results. Twenty seven trials were identified, most were six months of duration. The following combinations were included in the network meta-analysis: metformin (MET) + sulfonylureas (SU) (used as reference combination); MET + SU+ dipeptidyl peptidase 4 inhibitors (DPP-4-i); MET + SU+ thiazolidinediones (TZD); MET + SU+ glucagon-like peptide-1 receptor agonists (GLP-1-RA); MET + SU+ insulins; MET + TZD + DPP-4-i; and MET + SU+ sodium/glucose cotransporter 2 inhibitors (SGLT2-i). For HbA1c reduction, all triple therapies were statistically superior to MET+SU dual therapy, except for MET + TZD + DPP-4-i. None of the triple therapy combinations demonstrated differences in HbA1c compared with other triple therapies. MET + SU + SGLT2-i and MET + SU + GLP-1-RA resulted in significantly lower body weight than MET + SU + DPP-4-i, MET+SU+insulin and MET + SU + TZDs; MET + SU + DPP-4-i resulted in significantly lower body weight than MET + SU + insulin and MET + SU + TZD. MET + SU + insulin, MET + SU + TZD and MET + SU + DPP-4-i increased the odds of hypoglycaemia when compared to MET + SU. MET + SU + GLP-1-RA reduced the odds of hypoglycaemia compared to MET + SU + insulin. Conclusion. Care when choosing a triple therapy combination is needed as there is often a risk of increased hypoglycaemia events associated with this regimen and there are very limited data surrounding the long-term effectiveness and safety of combined therapies. PMID:26664803

  18. Combination and triple therapy in patients with stable angina pectoris not adequately controlled by optimal β-blocker therapy

    PubMed Central

    Kok, W.E.M.; Visser, F.C.; Visser, C.A.

    2002-01-01

    In 60 to 80% of patients with stable angina pectoris at low risk for future coronary events, monotherapy with a β-blocker is an effective treatment. When patients with stable angina pectoris and low risk for events do not respond adequately to optimal β-blocker monotherapy, combination therapy or even triple therapy is may be recommended, but little is known of the actual benefit of such a strategy. We reviewed the evidence from the literature on the effectiveness of combination and triple therapy. Combination therapy with a calcium antagonist or nitrate was found to be more effective than β-blocker monotherapy in the majority of studies, but only an estimated 30% of patients objectively benefit from these combination therapies. Direct comparison shows that combination therapy of a β-blocker with a calcium antagonist is more effective than the combination of a β-blocker with a nitrate. An inadequate response to β-blocker monotherapy is more effectively improved by addition of a calcium antagonist than by alternative use of a calcium antagonist. The use of triple therapy is controversial and not recommended in patients with mild angina pectoris, while for patients with severe angina pectoris not responding to combination therapy of a β-blocker with a nitrate, triple therapy may be of advantage, although the number of patients studied has been small. PMID:25696045

  19. Role of bismuth in improving Helicobacter pylori eradication with triple therapy.

    PubMed

    Dore, Maria Pina; Lu, Hong; Graham, David Y

    2016-05-01

    In most regions of the world, antimicrobial resistance has increased to the point where empirical standard triple therapy for Helicobacter pylorieradication is no longer recommended. The treatment outcome in a population is calculated as the sum of the treatment success in the subpopulation with susceptible infections plus treatment success in the subpopulation with resistant infections. The addition of bismuth (i.e., 14-day triple therapy plus bismuth) can improve cure rates despite a high prevalence of antimicrobial resistance. The major bismuth effect is to add an additional 30%-40% to the success with resistant infections. The overall result is therefore dependent on the prevalence of resistance and the treatment success in the subpopulation with resistant infections (eg, with proton-pump inhibitor-amoxicillin dual therapy). Here, we explore the contribution of each component and the mechanisms of how bismuth might enhance the effectiveness of triple therapy. We also discuss the limitations of this approach and provide suggestions how triple therapy plus bismuth might be further improved. PMID:26848181

  20. A Pilot Randomized Controlled Study of Dexlansoprazole MR-Based Triple Therapy for Helicobacter Pylori Infection

    PubMed Central

    Wu, Deng-Chyang; Kuo, Chao-Hung; Tsay, Feng-Woei; Hsu, Wen-Hung; Chen, Angela; Hsu, Ping-I

    2016-01-01

    Abstract Dexlansoprazole MR is the R-enantiomer of lansoprazole that is delivered by a dual delayed release formulation. It is effective for symptom control of patients with gastroesophageal reflux disease. However, its efficacy in the treatment of Helicobacter pylori infection remains unclear. This pilot, randomized, controlled, head-to-head study was conducted to investigate whether the efficacy of single-dose dexlansoprazole MR-based triple therapy was noninferior to double-dose rabeprazole-based triple therapy in the treatment of H pylori infection. Consecutive H pylori-infected subjects were randomly allocated to either 7-day dexlansoprazole MR-based standard triple therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily) or rabeprazole-based triple therapy (rabeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily). H pylori status was assessed 6 weeks after the end of treatment. A total of 177 H pylori-infected patients were randomized to receive dexlansoprazole MR-based (n = 90) or rabeprazole-based (n = 87) triple therapy. Intention-to-treat analysis demonstrated no differences between eradication rates of the 2 study groups (83.3% vs 81.6%; P = 0.736). Per-protocol analysis yielded comparable results (85.1% vs 81.2%; P = 0.497). Both groups exhibited similar frequencies of adverse events (7.8% vs 4.6%; P = 0.536) and drug compliance (98.9% vs 97.7%; P = 0.496). Multivariate analysis disclosed that the presence of clarithromycin resistance was the only independent factors predictive of treatment failure with an odds ratio of 6.8 (95% confidence interval: 1.2–37.6). This work demonstrates that single-dose dexlansoprazole MR-based triple therapy yields a similar eradication rate as double-dose rabeprazole-based therapy. Since the pharmaceutical cost of the single-dose dexlansoprazole MR regime is lower than that of the double

  1. A Pilot Randomized Controlled Study of Dexlansoprazole MR-Based Triple Therapy for Helicobacter Pylori Infection.

    PubMed

    Wu, Deng-Chyang; Kuo, Chao-Hung; Tsay, Feng-Woei; Hsu, Wen-Hung; Chen, Angela; Hsu, Ping-I

    2016-03-01

    Dexlansoprazole MR is the R-enantiomer of lansoprazole that is delivered by a dual delayed release formulation. It is effective for symptom control of patients with gastroesophageal reflux disease. However, its efficacy in the treatment of Helicobacter pylori infection remains unclear. This pilot, randomized, controlled, head-to-head study was conducted to investigate whether the efficacy of single-dose dexlansoprazole MR-based triple therapy was noninferior to double-dose rabeprazole-based triple therapy in the treatment of H pylori infection. Consecutive H pylori-infected subjects were randomly allocated to either 7-day dexlansoprazole MR-based standard triple therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily) or rabeprazole-based triple therapy (rabeprazole 20 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1 g twice daily). H pylori status was assessed 6 weeks after the end of treatment. A total of 177 H pylori-infected patients were randomized to receive dexlansoprazole MR-based (n = 90) or rabeprazole-based (n = 87) triple therapy. Intention-to-treat analysis demonstrated no differences between eradication rates of the 2 study groups (83.3% vs 81.6%; P = 0.736). Per-protocol analysis yielded comparable results (85.1% vs 81.2%; P = 0.497). Both groups exhibited similar frequencies of adverse events (7.8% vs 4.6%; P = 0.536) and drug compliance (98.9% vs 97.7%; P = 0.496). Multivariate analysis disclosed that the presence of clarithromycin resistance was the only independent factors predictive of treatment failure with an odds ratio of 6.8 (95% confidence interval: 1.2-37.6). This work demonstrates that single-dose dexlansoprazole MR-based triple therapy yields a similar eradication rate as double-dose rabeprazole-based therapy. Since the pharmaceutical cost of the single-dose dexlansoprazole MR regime is lower than that of the double-dose rabeprazole

  2. Telehealth and Occupational Therapy: Integral to the Triple Aim of Health Care Reform.

    PubMed

    Cason, Jana

    2015-01-01

    Programs and concepts included in the Patient Protection and Affordable Care Act of 2010 are expected to transform health care in the United States from a volume-based health system to a value-based health system with increased emphasis on prevention and health promotion. The Triple Aim, a framework set forth by the Institute for Healthcare Improvement, focuses on improving the health care experience, the health of populations, and the affordability of care. This article describes telehealth as an integral component in achieving the Triple Aim of health care and discusses implications for occupational therapy practitioners. PMID:26122676

  3. Surgery and radiation therapy of triple-negative breast cancers: From biology to clinics.

    PubMed

    Bernier, Jacques; Poortmans, Philip M P

    2016-08-01

    Triple negative breast cancer refers to tumours lacking the expression of the three most used tumour markers, namely oestrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). These cancers are known to carry a more dismal prognosis than the other molecular subtypes. Whether a more aggressive local-regional treatment is warranted or not in patients with triple-negative breast cancer is still a matter of debate. Indeed there remain a number of grey zones with respect to the optimization of the extent and the timing of surgery and radiation therapy (RT) in this patient population, also in consideration of the significant heterogeneity in biological behaviour and response to treatment identified for these tumours. The objective of this review is to provide an insight into the biological and clinical behaviour of triple-negative breast cancers and revisit the most recent advances in their management, focussing on local-regional treatments. PMID:27318170

  4. Sequential Therapy or Standard Triple Therapy for Helicobacter pylori Infection: An Updated Systematic Review.

    PubMed

    Feng, Li; Wen, Mao-Yao; Zhu, Yong-Jun; Men, Ruo-Ting; Yang, Li

    2016-01-01

    The effectiveness of standard triple therapy (STT) for the eradication of Helicobacter pylori has decreased recently. Sequential therapy (SQT) is a new regimen proposed to address this problem. The aim of this study was to compare the efficacy of SQT versus STT for H. pylori eradication. We searched The Cochrane Library, MEDLINE, Web of Science, and EMBASE databases up to July 2014. The risk ratios (RRs) of eradication rate were pooled, with a 95% confidence interval (CI). Thirty-six randomized clinical trials including a total of 10,316 patients met the inclusion criteria. The RR for eradication of H. pylori with SQT compared with STT was 1.14 (95% CI: 1.09-1.17), the eradication rates were 84.1% and 75.1%, respectively. There was significant heterogeneity between trial results (I = 73%; P < 0.00001). Subgroup analyses showed that SQT was superior to both 7- and 10-day STT, but not significantly better than 14-day STT. This superiority existed when patients were treated with either metronidazole or tinidazole. Patients with single clarithromycin-resistant strain showed a greater benefit of SQT over STT (eradication rates 80.9% vs. 40.7%), RR = 1.98 (95% CI: 1.33-2.94). There was no significant difference between groups in terms of the risk of adverse effects. In conclusion, SQT is more efficacious than STT (7 days and 10 days) in the eradication of HP, but the pooled rate seemed suboptimal. Further research is needed to develop more effective therapeutic approaches. Surveillance of resistance rates should be performed to guide treatment. PMID:25569598

  5. Single-pill triple-combination therapy: an alternative to multiple-drug treatment of hypertension.

    PubMed

    Chrysant, Steven G

    2011-11-01

    Hypertension (HTN) affects an estimated 76.4 million US adults. Despite improvements in blood pressure (BP) control rates and the availability of effective antihypertensive agents, only 50% of these individuals achieve BP control. It is now recognized that many patients will require ≥ 2 antihypertensive agents to achieve BP control. Both the current US and reappraisal of the 2007 European guidelines include dual-combination regimens among recommended treatments for initial HTN therapy. For patients requiring 3 drugs, the combination of agents with complementary mechanisms of action (ie, renin-angiotensin-aldosterone system blocker, calcium channel blocker, and diuretic) has been recognized as rational and effective. Three single-pill triple-drug combinations have recently been approved for use in HTN in the United States: valsartan (VAL)/amlodipine (AML)/hydrochlorothiazide (HCTZ); olmesartan medoxomil (OM)/AML/HCTZ; and aliskiren (ALI)/VAL/HCTZ. Triple-combination regimens have resulted in a greater proportion of patients achieving BP control compared with dual-combination regimens, with significantly lower BP levels documented after only 2 weeks at maximum doses. Single-pill combinations offer convenience to address barriers to BP control such as poor adherence to therapy and therapeutic inertia. Additional benefits of combining antihypertensive agents from different classes include improved efficacy, safety, and reduction of cardiovascular risk. In patients with essential HTN for whom dual therapy is inadequate, single-pill triple-drug therapy can offer a simplified and effective treatment strategy. PMID:22104451

  6. Evaluation of factors associated with relapse in telaprevir-based triple therapy for chronic hepatitis C

    PubMed Central

    Kondo, C; Atsukawa, M; Tsubota, A; Shimada, N; Abe, H; Aizawa, Y

    2016-01-01

    Background and Rationale: Most patients with chronic hepatitis C show virological response to telaprevir-based triple therapy, and achieve an end-of-treatment response (ETR). However, some patients showing ETR develop virological relapse. This study was carried out to evaluate factors associated with relapse after triple therapy. Materials and Methods: A prospective, multicentric study was conducted in chronic hepatitis C patients who received telaprevir-based triple therapy. We evaluated independent variables such as age, with or without cirrhosis, prior treatment response to interferon (IFN) therapy, IL28B genotype, core amino acid (aa) 70 mutation, drug adherence, white blood cell counts, hemoglobin level, and serum low-density lipoprotein (LDL) cholesterol level. The characteristics of the patients who relapsed after achieving ETR were compared with those who did not. Results: Among 168 patients, 157 patients achieved ETR (93.5%) and 11 discontinued. Of these 157 patients, relapse occurred in 21 patients (13.4%). Nineteen patients (90.5%) of 21 relapsed patients had the IL28B non-TT genotype (P = 1.79 × 10-9). Multivariate analysis identified core amino acid 70 [P = 0.018, crude odds ratio (OR): 6.927] and the IL28B genotype (P = 3.758 × 10-5, crude OR: 39.311) as significantly independent factors that influenced the relapse-related variables. Among the 49 patients with the IL28B non-TT, 18 patients had core aa70 mutation and 31 patients had core aa70 wild-type. In addition, 66.7% (12/18) of those with core aa70 mutation and 22.6% (7/31) of those with core aa70 wild-type developed relapse (P = 0.005). Discussion: Core aa70 mutation and the IL28B non-TT genotype were identified as independent factors that influenced relapse after achievement of ETR for telaprevir-based triple therapy. PMID:26732192

  7. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    PubMed

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel

    2014-07-01

    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. PMID:25907434

  8. Triple therapy for percutaneous coronary intervention in atrial fibrillation: standard of care, or a nightmare soon to end?

    PubMed

    Verheugt, F W A

    2015-06-01

    The need to combine anticoagulant and antiplatelet therapy ('triple therapy') in patients with atrial fibrillation and coronary artery disease increases the risk of bleeding. As percutaneous intervention is now the dominant therapy for coronary disease, clinicians question how to manage the risk of stroke in patients with atrial fibrillation and a coronary stent that require dual antiplatelet therapy. In this review, the risk of stroke and coronary thrombosis in this difficult group of patients will be summarized using current recommendations and guidelines. The scarce randomized data on triple therapy are reviewed, and there will be a focus on currently running trials on this topic. PMID:26149044

  9. Novel Microdilution Method to Assess Double and Triple Antibiotic Combination Therapy In Vitro

    PubMed Central

    El-Azizi, Mohamed

    2016-01-01

    An in vitro microdilution method was developed to assess double and triple combinations of antibiotics. Five antibiotics including ciprofloxacin, amikacin, ceftazidime, piperacillin, and imipenem were tested against 10 clinical isolates of Pseudomonas aeruginosa. Each isolate was tested against ten double and nine triple combinations of the antibiotics. A 96-well plate was used to test three antibiotics, each one alone and in double and triple combinations against each isolate. The minimum bacteriostatic and bactericidal concentrations in combination were determined with respect to the most potent antibiotic. An Interaction Code (IC) was generated for each combination, where a numerical value was designated based on the 2-fold increase or decrease in the MICs with respect to the most potent antibiotic. The results of the combinations were verified by time-kill assay at constant concentrations of the antibiotics and in a chemostat. Only 13% of the double combinations were synergistic, whereas 5% showed antagonism. Forty-three percent of the triple combinations were synergistic with no antagonism observed, and 100% synergism was observed in combination of ciprofloxacin, amikacin, and ceftazidime. The presented protocol is simple and fast and can help the clinicians in the early selection of the effective antibiotic therapy for treatment of severe infections. PMID:27195009

  10. Triple Therapy with First Generation Protease Inhibitors for Hepatitis C Markedly Impairs Function of Neutrophil Granulocytes.

    PubMed

    Spindelboeck, Walter; Horvath, Angela; Tawdrous, Monika; Schmerböck, Bianca; Zettel, Gabriele; Posch, Andreas; Streit, Andrea; Jurse, Petra; Lemesch, Sandra; Horn, Martin; Wuensch, Gerit; Stiegler, Philipp; Stauber, Rudolf E; Leber, Bettina; Stadlbauer, Vanessa

    2016-01-01

    First-generation HCV protease inhibitors represent a milestone in antiviral therapy for chronic hepatitis C infection (CHC), but substantially increased rates of viral clearance are offset by increased rates of infection and infection-associated deaths, especially of patients with advanced liver disease. We aimed to assess whether first generation protease inhibitors interfere with neutrophil function. We included 108 consecutive, retrospective CHC patients and 44 consecutive, prospective CHC patients who were treated with peginterferon and ribavirin with or without protease inhibitors according to the guidelines in the period of November 2012 to June 2015. 33 healthy volunteers served as controls. Infection data were evaluated in all patients. Neutrophil phagocytosis, oxidative burst, elastase and diamine oxidase levels during 12 weeks of triple (n = 23) or dual therapy (n = 21) were studied in the prospective part. In the retro- and prospective cohorts patients experiencing clinically relevant infections were significantly more frequent during protease inhibitor therapy (31% and 26%) than during therapy with peginterferon and ribavirin (13% and 0%). Neutrophil phagocytosis decreased to 40% of baseline with addition of protease inhibitors to P/R but recovered 6 months after end of treatment. Protease inhibitors also seemed to reduce serum elastase levels but did not impact on gut permeability. Impaired neutrophil function during triple therapy with first generation HCV protease inhibitors may explain the high infection rate associated to these treatments and be of relevance for treatment success and patient survival. PMID:26938078

  11. Triple Therapy with First Generation Protease Inhibitors for Hepatitis C Markedly Impairs Function of Neutrophil Granulocytes

    PubMed Central

    Tawdrous, Monika; Schmerböck, Bianca; Zettel, Gabriele; Posch, Andreas; Streit, Andrea; Jurse, Petra; Lemesch, Sandra; Horn, Martin; Wuensch, Gerit; Stiegler, Philipp; Stauber, Rudolf E.; Leber, Bettina; Stadlbauer, Vanessa

    2016-01-01

    First-generation HCV protease inhibitors represent a milestone in antiviral therapy for chronic hepatitis C infection (CHC), but substantially increased rates of viral clearance are offset by increased rates of infection and infection-associated deaths, especially of patients with advanced liver disease. We aimed to assess whether first generation protease inhibitors interfere with neutrophil function. We included 108 consecutive, retrospective CHC patients and 44 consecutive, prospective CHC patients who were treated with peginterferon and ribavirin with or without protease inhibitors according to the guidelines in the period of November 2012 to June 2015. 33 healthy volunteers served as controls. Infection data were evaluated in all patients. Neutrophil phagocytosis, oxidative burst, elastase and diamine oxidase levels during 12 weeks of triple (n = 23) or dual therapy (n = 21) were studied in the prospective part. In the retro- and prospective cohorts patients experiencing clinically relevant infections were significantly more frequent during protease inhibitor therapy (31% and 26%) than during therapy with peginterferon and ribavirin (13% and 0%). Neutrophil phagocytosis decreased to 40% of baseline with addition of protease inhibitors to P/R but recovered 6 months after end of treatment. Protease inhibitors also seemed to reduce serum elastase levels but did not impact on gut permeability. Impaired neutrophil function during triple therapy with first generation HCV protease inhibitors may explain the high infection rate associated to these treatments and be of relevance for treatment success and patient survival. Trial Registration ClinicalTrials.gov NCT02545400 ClinicalTrials.gov NCT02545335 PMID:26938078

  12. Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication.

    PubMed

    Trifan, Anca; Girleanu, Irina; Cojocariu, Camelia; Sfarti, Catalin; Singeap, Ana Maria; Dorobat, Carmen; Grigore, Lucia; Stanciu, Carol

    2013-11-14

    Helicobacter pylori (H. pylori) is one of the most common chronic bacterial infections in humans, affecting half of world's population. Therapy for H. pylori infection has proven to be both effective and safe. The one-week triple therapy including proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H. pylori infection in countries with low clarithromycin resistance. Generally, this therapy is well-tolerated, with only a few and usually minor side effects. However, rare but severe adverse effects such as pseudomembranous colitis have been reported, Clostridium difficile (C. difficile) infection being the main causative factor in all cases. We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid, clarithromycin 500 mg bid, and amoxicillin 1 g bid to eradicate H. pylori infection. A limited colonoscopy showed typical appearance of pseudomembranous colitis, and the stool test for C. difficile toxins was positive. Rapid resolution of symptoms and negative C. difficile toxins were obtained in both patients with oral vancomycin. No relapse occurred during a four and eleven-month, respectively, follow up. These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H. pylori eradication therapy. PMID:24259981

  13. Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

    PubMed Central

    Trifan, Anca; Girleanu, Irina; Cojocariu, Camelia; Sfarti, Catalin; Singeap, Ana Maria; Dorobat, Carmen; Grigore, Lucia; Stanciu, Carol

    2013-01-01

    Helicobacter pylori (H. pylori) is one of the most common chronic bacterial infections in humans, affecting half of world’s population. Therapy for H. pylori infection has proven to be both effective and safe. The one-week triple therapy including proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H. pylori infection in countries with low clarithromycin resistance. Generally, this therapy is well-tolerated, with only a few and usually minor side effects. However, rare but severe adverse effects such as pseudomembranous colitis have been reported, Clostridium difficile (C. difficile) infection being the main causative factor in all cases. We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid, clarithromycin 500 mg bid, and amoxicillin 1 g bid to eradicate H. pylori infection. A limited colonoscopy showed typical appearance of pseudomembranous colitis, and the stool test for C. difficile toxins was positive. Rapid resolution of symptoms and negative C. difficile toxins were obtained in both patients with oral vancomycin. No relapse occurred during a four and eleven-month, respectively, follow up. These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H. pylori eradication therapy. PMID:24259981

  14. Randomized Controlled Trial Comparing 7-Day Triple, 10-Day Sequential, and 7-Day Concomitant Therapies for Helicobacter pylori Infection

    PubMed Central

    Hsu, Ping-I; Wu, Deng-Chyang; Chen, Wen-Chi; Tseng, Hui-Hwa; Yu, Hsien-Chung; Wang, Huay-Min; Kao, Sung-Shuo; Lai, Kwok-Hung; Chen, Angela

    2014-01-01

    With the rising prevalence of antimicrobial resistance, the failure rate of the standard triple therapy for Helicobacter pylori infection is increasing. Sequential therapy and concomitant therapy have been recommended to replace standard triple therapy for H. pylori eradication in regions with high clarithromycin resistance. The aim of this prospective, randomized, and controlled study was to simultaneously assess the efficacies of 10-day sequential and 7-day concomitant therapies versus a 7-day standard triple therapy for treating H. pylori infection. Consecutive H. pylori-infected subjects were randomly assigned to a 7-day standard triple therapy (pantoprazole, clarithromycin, and amoxicillin for 7 days), a 10-day sequential therapy (pantoprazole and amoxicillin for 5 days, followed by pantoprazole, clarithromycin, and metronidazole for a further 5 days), or a 7-day quadruple therapy (pantoprazole, clarithromycin, amoxicillin, and metronidazole for 7 days). H. pylori status was confirmed 6 weeks after therapy. Three hundred seven H. pylori-infected participants were randomized to receive triple (n = 103), sequential (n = 102), or concomitant (n = 102) therapies. The eradication rates by an intention-to-treat analysis in the three treatment groups were 81.6% (95% confidence interval [CI], 74.1% to 89.0%), 89.2% (95% CI, 83.2% to 95.2%), and 94.1% (95% CI, 89.5% to 98.7%). The seven-day concomitant therapy had a higher eradication rate than did the 7-day triple therapy (difference, 12.5%; 95% CI, 3.7% to 21.3%). There were no significant differences in the eradication rates between the sequential and standard triple therapies. All three treatments exhibited similar frequencies of adverse events (8.7%, 8.8%, and 13.7%, respectively) and drug compliance (99.0%, 98.0%, and 100.0%, respectively). In conclusion, the seven-day concomitant therapy is superior to the 7-day standard triple therapy for H. pylori eradication. Additionally, it is less complex than the 10-day

  15. Helicobacter pylori is not eradicated after triple therapy: a nested PCR based study.

    PubMed

    Patel, Saurabh Kumar; Mishra, Girish Narayan; Pratap, Chandra Bhan; Jain, Ashok Kumar; Nath, Gopal

    2014-01-01

    Detection of Helicobacter pylori after triple therapy is usually carried out by either rapid urease test (RUT), urea breath test (UBT), histology, bacterial isolation, and single round PCR or serological tests. In this study, antral biopsy specimens from 25 patients were tested for H. pylori by RUT, culture, histology, and nested PCR in their antral biopsy specimens before and after treatment. Three genes, namely, heat shock protein (hsp60), phosphoglucosamine mutase (ureC), and flagellar export ATP synthase (fliI) of H. pylori were targeted. Of the 25 antral biopsy specimens, the RUT, culture, histology, and nested PCR positivity dropped from 81.8% to 12%, 31% to 0%, 100 to 84%, and 100% to 92%, respectively, before and after therapy. Further, hsp60 specific amplicons from 23 out of 25 patients gave identical restriction pattern, while 6 fliI and 1 ureC specific amplicon produced different restriction pattern. Furthermore, variations in fliI gene sequences in H. pylori after treatment were also confirmed by sequencing and compared in silico. Nested PCR based detection of H. pylori is more sensitive method to detect H. pylori after therapy than culture, RUT, and histology. Further, this study suggests that H. pylori is not eradicated completely after triple therapy. PMID:25054141

  16. Standard Triple Therapy versus Sequential Therapy in Helicobacter pylori Eradication: A Double-Blind, Randomized, and Controlled Trial

    PubMed Central

    Navarro-Rodriguez, Tomás; Teixeira, Ana Cristina Sá; Silva, Fernando Marcuz; Mattar, Rejane; Chinzon, Decio; Haro, Christiane; Moraes-Filho, Joaquim Prado; Fass, Ronnie; Barbuti, Ricardo Correa

    2015-01-01

    Aim. To compare 10-day standard triple therapy versus sequential therapy as first-line treatment in patients infected with H. pylori. Methods. One hundred H. pylori positive patients (diagnosed by rapid urease test and histology), with average age of 47.2, M/F = 28/72, were randomized to receive either standard triple treatment (TT) as follows: lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 g, b.i.d. for ten days, or sequential treatment (ST) as follows: lansoprazole 30 mg, amoxicillin and placebo 1.0 g b.i.d for the first five days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and tinidazole 500 mg b.i.d, for the remaining five days. Eradication rates were determined 60 days after treatment by urease, histology, or 13C-urea breath test. Results. In intention to treat (ITT) analysis, the rate of H. pylori eradication in the TT and ST groups was the same for both regimens as follows: 86% (43/50), 95% CI 93,3 to 73.4%. In Per protocol (PP) analysis, the rate of H. pylori eradication in the TT and ST groups was 87.8% (43/49), 95% CI 94,5 to 75.3% and 89.6% (43/48), 95% CI 95,8 to 77.3%, respectively. Conclusions. In Brazil, standard triple therapy is as equally effective as sequential therapy in eradicating Helicobacter pylori patients. This study was registered under Clinical Trials with number ISRCTN62400496. PMID:26064098

  17. Moxifloxacine plus amoxicillin and ranitidine bismuth citrate or esomeprazole triple therapies for Helicobacter pylori infection.

    PubMed

    Kiliç, Zeki Mesut Yalin; Köksal, Aydin Seref; Cakal, Başak; Nadir, Işilay; Ozin, Yasemin Ozderin; Kuran, Sedef; Sahin, Burhan

    2008-12-01

    Up to 20% of patients, or even more, will fail to obtain eradication after a standard triple therapy. The aim of this study is to evaluate the efficacy of moxifloxacine-containing regimens in the first-line treatment of Helicobacter pylori. One hundred and twenty H. pylori-positive patients were randomized into four groups to receive one of the following 14-day treatments: ranitidine bismuth citrate (RBC) 400 mg b.d. plus amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (RAC group, n = 30); RBC 400 mg b.d. plus moxifloxacine 400 mg o.d. and amoxicillin 1,000 mg b.d. (RAM group, n = 30); esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus clarithromycin 500 mg b.d. (EAC group, n = 30); and esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus moxifloxacine 400 mg o.d. (EAM group, n = 30). Eradication was assessed by (13)C urea breath test 8 weeks after therapy. Per-protocol and intention-to-treat eradication was achieved in 23 out of 30 patients (76.7%, 95% confidence interval [CI]: 61-92) in the RAC group, in 20 patients (66.7%, 95% CI: 49-84) in the RAM group, in 16 patients in the EAM group (53.3%, 95% CI: 34-71), and in 19 patients in the EAC group (63.3%, 95% CI: 54-72). Mild or moderate side-effects were significantly more common in the EAM group (70%) compared to the RAC (36.6%), RAM (43.3%), and EAC (56.6%) groups (P = 0.03). From our results, we conclude that moxifloxacine-containing triple therapies have neither eradication nor compliance advantages over standard triple therapies. Further studies with new antibiotic associations are needed for the better eradication of H. pylori in developing regions of the world. PMID:18465244

  18. Rapid Extensive Recurrence of Triple Negative Breast Cancer: Are Both Therapy and Cancer Biology the Culprit?

    PubMed

    Vyas, Dinesh; Deshpande, Kaivalya; Chaturvedi, Lakshmishankar; Gieric, Laput; Ching, Karen

    2016-02-01

    Triple negative breast cancer (TNBC) comprises 17-20% of all breast cancers and is one of the most common breast cancers. The lack of therapy and failure of existing therapy has been a challenge for clinicians. Doxorubicin (DOX) is the first-line therapy, however, it has significant limitations. Rapid extensive recurrence with metastasis in any cancer has been a challenge for surgeons and medical oncologists. The challenge can be due to failure of therapy, drug resistance, or epigenetic changes. Here, we are discussing a stage I breast cancer patient, operated and treated with appropriate chemotherapy with complete response, which recurred in less than 8 months and metastasized to bone, liver and other organs. We are also presenting lab data of the IL-6 secretions on exposure to DOX in one of the most commonly used TNBC cell lines MDA-MB-231. Breast cancer cell line MDA-MB-231 upon exposure to DOX shows an increase in IL-6 levels more than the already elevated IL-6 levels. This might be a reason for early recurrence. We concluded that patients with TNBC might benefit from a standard DOX treatment regimen with an inflammation-blocking agent. PMID:26767086

  19. Rapid Extensive Recurrence of Triple Negative Breast Cancer: Are Both Therapy and Cancer Biology the Culprit?

    PubMed Central

    Vyas, Dinesh; Deshpande, Kaivalya; Chaturvedi, Lakshmishankar; Gieric, Laput; Ching, Karen

    2016-01-01

    Triple negative breast cancer (TNBC) comprises 17-20% of all breast cancers and is one of the most common breast cancers. The lack of therapy and failure of existing therapy has been a challenge for clinicians. Doxorubicin (DOX) is the first-line therapy, however, it has significant limitations. Rapid extensive recurrence with metastasis in any cancer has been a challenge for surgeons and medical oncologists. The challenge can be due to failure of therapy, drug resistance, or epigenetic changes. Here, we are discussing a stage I breast cancer patient, operated and treated with appropriate chemotherapy with complete response, which recurred in less than 8 months and metastasized to bone, liver and other organs. We are also presenting lab data of the IL-6 secretions on exposure to DOX in one of the most commonly used TNBC cell lines MDA-MB-231. Breast cancer cell line MDA-MB-231 upon exposure to DOX shows an increase in IL-6 levels more than the already elevated IL-6 levels. This might be a reason for early recurrence. We concluded that patients with TNBC might benefit from a standard DOX treatment regimen with an inflammation-blocking agent. PMID:26767086

  20. A comparison between standard triple therapy and sequential therapy on eradication of Helicobacter pylori in uremic patients: A randomized clinical trial

    PubMed Central

    Makhlough, Atieh; Fakheri, Hafez; Farkhani, Ahmad Ramezani; Seddighi, Omid; Hossieni, Seyed Vahid; Khademloo, Mohammad; Bari, Zohreh

    2014-01-01

    Background: The prevalence of peptic ulcer disease in hemodialysis dependent patients is higher than the general population. These patients are also more prone to upper gastrointestinal bleeding. The aim of this study was to compare the effects of a standard triple therapy with a sequential therapy on Helicobacter pylori eradication in azotemic and hemodialysis patients. Materials and Methods: Forty nine hemodialysis and azotemic patients, naïve to H. pylori treatment, were randomized into two groups to receive either standard triple therapy (pantoprazole 40 mg, amoxicillin 500 mg and clarithromycin 250 mg twice a day for 14 days) or a sequential therapy (pantoprazole 40 mg for 10 days, amoxicillin 500 mg twice a day for the first 5 days and clarithromycin 250 mg + tinidazole 500 mg twice a day just during the second 5 days). H. pylori eradication was evaluated by fecal H. pylori antigen assessment 8 weeks after the treatment. Results: Of 49 patients, 45 patients (21 in triple therapy group and 24 in the sequential group) completed the study. Based on intention to treat analysis, H. pylori eradication rates were 66.7% (95% confidence interval [CI]: 47.8-85.5%) in standard triple therapy group and 84% (95% CI: 69.6-98.3%) in sequential therapy group (P = 0.34). Per-protocol (PP) eradication rates were (95% CI: 76.2%. 6-89.3%) 54 and 87.5% (95% CI: 68.8-95.5%), respectively (P = 0.32). Conclusion: According to Maastricht III consensus report, the results of our study showed that sequential therapy might be a better choice compared with the standard triple therapy in azotemic and hemodialysis patients Iran. We propose to assess the effects of shorter-duration sequential therapy (less than 10 days) for H. pylori eradication. PMID:25590026

  1. Tumor-Associated Macrophage-Mediated Targeted Therapy of Triple-Negative Breast Cancer.

    PubMed

    Niu, Mengmeng; Valdes, Solange; Naguib, Youssef W; Hursting, Stephen D; Cui, Zhengrong

    2016-06-01

    Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer. TNBC is often infiltrated with a large number of macrophages, which in turn promote tumor growth and metastasis. In this study, tumor-associated macrophages (TAMs) were exploited as a target to deliver doxorubicin (DOX), a chemotherapeutic agent, to TNBC using nanoparticles surface-functionalized by (i) acid-sensitive sheddable PEGylation and (ii) modifying with mannose (i.e., DOX-AS-M-PLGA-NPs). In mice with orthotopic M-Wnt triple-negative mammary tumors, a single intravenous injection of DOX-AS-M-PLGA-NPs significantly reduced macrophage population in tumors within 2 days, and the density of the macrophages recovered slowly. Repeated injections of DOX-AS-M-PLGA-NPs can help maintain the population of the macrophages at a lower level. In M-Wnt tumor-bearing mice that were pretreated with zoledronic acid to nonselectively deplete macrophages, the TAM-targeting DOX-AS-M-PLGA-NPs were not more effective than the DOX-AS-PLGA-NPs that were not surface-modified with mannose and thus do not target TAMs in controlling tumor growth. However, in M-Wnt tumor-bearing mice that were not pretreated with zoledronic acid, the TAM-targeting DOX-AS-M-PLGA-NPs were significantly more effective than the nontargeting DOX-AS-PLGA-NPs in controlling the tumor growth. The AS-M-PLGA-NPs or other nanoparticles surface-functionalized similarly, when loaded with a chemotherapeutic agent commonly used in adjuvant therapy of TNBC, may be developed into targeted therapy for TNBC. PMID:27074028

  2. Triple Combination Therapy for Global Cardiovascular Risk: Atorvastatin, Perindopril, and Amlodipine.

    PubMed

    Bertrand, Michel E; Vlachopoulos, Charalambos; Mourad, Jean-Jacques

    2016-08-01

    Statins, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers (CCBs) have markedly changed the clinical progression of patients with coronary artery disease (CAD). The goal of this paper is to review the rationale and evidence for combining these three drug classes in hypertensive patients with hypercholesterolemia or CAD. Data sources include a literature search for publications on the use of a statin combined with various antihypertensive drugs in patients with hypertension and hypercholesterolemia or stable CAD. Hypercholesterolemia and hypertension constitute major physiological risk factors of ischemic heart disease. Current guidelines recommend a global approach to risk management, using agents that address as many risk factors as possible. Dual combination therapies are an important component of guideline-recommended therapy in hypertension. Our review of the literature indicates that triple therapy with a statin, ACE inhibitor, and CCB is associated with a significant reduction in major cardiovascular events. For example, a post hoc analysis in 1056 patients with stable CAD participating in the EUROPA trial indicated that the addition of perindopril to a CCB and a lipid-lowering agent was associated with a 46 % reduction in the composite of cardiovascular death, myocardial infarction, and resuscitated cardiac arrest (p = 0.023). In addition, single pill formulations are known to result in better adherence to the treatment. Single-pill formulations that combine a statin, an ACE inhibitor, and a CCB appear to offer an effective approach to the management of global cardiovascular risk. PMID:27256435

  3. Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy

    PubMed Central

    López-Ozuna, Vanessa M.; Hachim, Ibrahim Y.; Hachim, Mahmood Y.; Lebrun, Jean-Jacques; Ali, Suhad

    2016-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous disease associated with poor clinical outcome and lack of targeted therapy. Here we show that prolactin (PRL) and its signaling pathway serve as a sub-classifier and predictor of pro-differentiation therapy in TNBC. Using immunohistochemistry and various gene expression in silica analyses we observed that prolactin receptor (PRLR) protein and mRNA levels are down regulated in TNBC cases. In addition, examining correlation of PRLR gene expression with metagenes of TNBC subtypes (580 cases), we found that PRLR gene expression sub-classifies TNBC patients into a new subgroup (TNBC-PRLR) characterized by epithelial-luminal differentiation. Importantly, gene expression of PRL signaling pathway components individually (PRL, PRLR, Jak2 and Stat5a), or as a gene signature is able to predict TNBC patients with significantly better survival outcomes. As PRL hormone is a druggable target we determined the biological role of PRL in TNBC biology. Significantly, restoration/activation of PRL pathway in TNBC cells representative of mesenchymal or TNBC-PRLR subgroups led to induction of epithelial phenotype and suppression of tumorigenesis. Altogether, these results offer potential new modalities for TNBC stratification and development of personalized therapy based on PRL pathway activation. PMID:27480353

  4. Multifunctional hollow gold nanoparticles designed for triple combination therapy and CT imaging.

    PubMed

    Park, Jaesook; Park, Jin; Ju, Eun Jin; Park, Seok Soon; Choi, Jinhyang; Lee, Jae Hee; Lee, Kyoung Jin; Shin, Seol Hwa; Ko, Eun Jung; Park, Intae; Kim, Chulhee; Hwang, Jung Jin; Lee, Jung Shin; Song, Si Yeol; Jeong, Seong-Yun; Choi, Eun Kyung

    2015-06-10

    Hollow gold nanoparticles (HGNP) are a novel class of hybrid metal nanoparticles whose unique optical and morphological properties have spawned new applications including more effective cancer therapy. The shell thickness of HGNPs can tune the surface plasmon resonance to the near infrared light, resulting in photothermal ablation of tumors with optimal light penetration in tissue. The hollow cavity within a HGNP is able to accommodate a high payload of chemotherapeutic agents. They have also been used for enhancing radiosensitization in tumors during radiotherapy due to the high X-ray absorption capability of gold particles. However, no report has yet been published that utilize HGNPs for the triple combination therapy and CT imaging. In this study, we synthesized HGNPs which exhibit better response to radiation for therapy and imaging and demonstrated the effects of combined chemotherapy, thermal and radiotherapy. This combination strategy presented delayed tumor growth by 4.3-fold and reduced tumor's weight by 6.8-fold compared to control tumors. In addition, we demonstrated the feasibility of HGNP as a CT imaging agent. It is expected that translating these capabilities to human cancer patients could dramatically increase the antitumor effect and potentially overcome resistance to chemotherapeutic agents and radiation. PMID:25863273

  5. Sequential Therapy versus Triple Therapy for the First Line Treatment of Helicobacter pylori in Korea: A Nationwide Randomized Trial

    PubMed Central

    Kim, Joon Sung; Kim, Byung-Wook; Hong, Su Jin; Kim, Jin Il; Shim, Ki-Nam; Kim, Jie-Hyun; Baik, Gwang Ho; Kim, Sang Wook; Song, Hyun Joo; Kim, Ji Hyun

    2016-01-01

    Background/Aims Eradication of Helicobacter pylori infection with standard triple therapy (TT) has declined primarily because of increased antibiotic resistance. Sequential therapy (ST) has been suggested as an alternative to TT for the first-line treatment of H. pylori. The purpose of this study was to compare the efficacy of ST with TT. Methods This was a multicenter, randomized open-label trial performed at nine centers in Korea. Patients with H. pylori infection were randomly assigned to receive either 7 day TT or 10 day ST. Eradication rates, drug compliance, and adverse events were compared among the two regimens. Results A total of 601 patients were enrolled between March 2011 and September 2014. The intention-to-treat eradication rates were 70.8% for TT and 82.4% for ST (p=0.001). The corresponding per protocol eradication rates were 76.9% and 88.8% for TT and ST, respectively (p=0.000). There were no statistically significant differences between the two regimens with respect to drug compliance and adverse events. Conclusions ST achieved better eradication rates than TT as a first-line therapy for H. pylori eradication in Korea. PMID:27114421

  6. Effects of Demographics on the Antihypertensive Efficacy of Triple Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide for Moderate to Severe Hypertension

    PubMed Central

    Calhoun, David A.; Lacourci00E8;re, Yves; Crikelair, Nora; Jia, Yan; Glazer, Robert D.

    2014-01-01

    Objective To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320 mg, and hydrochlorothiazide (HCTZ) 25 mg versus dual-therapy combinations of these components in patients with moderate to severe hypertension. Research design Subgroup analysis of a multinational, randomized, double-blind, parallel-group, active-controlled trial. Methods After antihypertensive washout and a placebo run-in of up to 4 weeks, 2271 patients were randomly allocated in a 1:1:1:1 ratio to receive Aml/Val/HCTZ triple therapy or dual therapy with Val/HCTZ, Aml/Val, or Aml/HCTZ for 8 weeks. Forced titration to the full dose was done over the first 2 weeks of treatment. Efficacy and safety parameters were determined by age group (<65 vs. ≥65 years), gender, race (White vs. Black), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), and body mass index (BMI, <30 vs. ≥30 kg/m2). Main outcome measures Change from baseline to endpoint in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP); blood pressure (BP) control rate <140/90 mmHg. Results Triple therapy was numerically superior and, for the majority of comparisons, statistically superior to each dual therapy in reducing MSSBP and MSDBP and in improving BP control rates in all subgroups. Across subgroups, triple therapy reduced MSSBP by 5.7–10.7 mmHg more than Val/HCTZ, 3.4–8.3 mmHg more than Aml/Val, and 4.4–9.4 mmHg more than Aml/HCTZ. Triple therapy was well tolerated across all subgroups. Limitations of our analysis included the lack of stratification of patients by subgroup at randomization and the small sample size of some subgroups (eg, Blacks, elderly). Conclusions Triple therapy with Aml/Val/HCTZ is effective and well tolerated in patients with moderate to severe hypertension regardless of age, gender, race, ethnicity, or BMI. PMID:23721363

  7. Triple therapy of interferon and ribavirin with zinc supplementation for patients with chronic hepatitis C: A randomized controlled clinical trial

    PubMed Central

    Suzuki, Hideyuki; Takagi, Hitoshi; Sohara, Naondo; Kanda, Daisuke; Kakizaki, Satoru; Sato, Ken; Mori, Masatomo

    2006-01-01

    AIM: To study the therapeutic effect of interferon (IFN) and ribavirin with zinc supplement on patients with chronic hepatitis C viral (HCV) infection. METHODS: A total of 102 patients confirmed histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon (IFN-alpha-2b) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin (600 or 800 mg/d depending on body weight), with or without polaprezinc (150 mg/d) orally for 24 wk. The primary endpoint was sustained virological response (SVR) defined as negative HCV-RNA in the serum 6 mo after treatment. RESULTS: There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group (P< 0.05). SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group (P = 0.019). CONCLUSION: Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects. PMID:16534882

  8. Triple therapy with pyridoxine, arginine supplementation and dietary lysine restriction in pyridoxine-dependent epilepsy: Neurodevelopmental outcome.

    PubMed

    Coughlin, Curtis R; van Karnebeek, Clara D M; Al-Hertani, Walla; Shuen, Andrew Y; Jaggumantri, Sravan; Jack, Rhona M; Gaughan, Sommer; Burns, Casey; Mirsky, David M; Gallagher, Renata C; Van Hove, Johan L K

    2015-01-01

    Pyridoxine-dependent epilepsy (PDE) is an epileptic encephalopathy characterized by response to pharmacologic doses of pyridoxine. PDE is caused by deficiency of α-aminoadipic semialdehyde dehydrogenase resulting in impaired lysine degradation and subsequent accumulation of α-aminoadipic semialdehyde. Despite adequate seizure control with pyridoxine monotherapy, 75% of individuals with PDE have significant developmental delay and intellectual disability. We describe a new combined therapeutic approach to reduce putative toxic metabolites from impaired lysine metabolism. This approach utilizes pyridoxine, a lysine-restricted diet to limit the substrate that leads to neurotoxic metabolite accumulation and L-arginine to compete for brain lysine influx and liver mitochondrial import. We report the developmental and biochemical outcome of six subjects who were treated with this triple therapy. Triple therapy reduced CSF, plasma, and urine biomarkers associated with neurotoxicity in PDE. The addition of arginine supplementation to children already treated with dietary lysine restriction and pyridoxine further reduced toxic metabolites, and in some subjects appeared to improve neurodevelopmental outcome. Dietary lysine restriction was associated with improved seizure control in one subject, and the addition of arginine supplementation increased the objective motor outcome scale in two twin siblings, illustrating the contribution of each component of this treatment combination. Optimal results were noted in the individual treated with triple therapy early in the course of the disease. Residual disease symptoms could be related to early injury suggested by initial MR imaging prior to initiation of treatment or from severe epilepsy prior to diagnosis. This observational study reports the use of triple therapy, which combines three effective components in this rare condition, and suggests that early diagnosis and treatment with this new triple therapy may ameliorate the

  9. Molecular phenotypes in triple negative breast cancer from African American patients suggest targets for therapy.

    PubMed

    Lindner, Robert; Sullivan, Catherine; Offor, Onyinye; Lezon-Geyda, Kimberly; Halligan, Kyle; Fischbach, Neal; Shah, Mansi; Bossuyt, Veerle; Schulz, Vincent; Tuck, David P; Harris, Lyndsay N

    2013-01-01

    Triple negative breast cancer (TNBC) is characterized by high proliferation, poor differentiation and a poor prognosis due to high rates of recurrence. Despite lower overall incidence African American (AA) patients suffer from higher breast cancer mortality in part due to the higher proportion of TNBC cases among AA patients compared to European Americans (EA). It was recently shown that the clinical heterogeneity of TNBC is reflected by distinct transcriptional programs with distinct drug response profiles in preclinical models. In this study, gene expression profiling and immunohistochemistry were used to elucidate potential differences between TNBC tumors of EA and AA patients on a molecular level. In a retrospective cohort of 136 TNBC patients, a major transcriptional signature of proliferation was found to be significantly upregulated in samples of AA ethnicity. Furthermore, transcriptional profiles of AA tumors showed differential activation of insulin-like growth factor 1 (IGF1) and a signature of BRCA1 deficiency in this cohort. Using signatures derived from the meta-analysis of TNBC gene expression carried out by Lehmann et al., tumors from AA patients were more likely of basal-like subtypes whereas transcriptional features of many EA samples corresponded to mesenchymal-like or luminal androgen receptor driven subtypes. These results were validated in The Cancer Genome Atlas mRNA and protein expression data, again showing enrichment of a basal-like phenotype in AA tumors and mesenchymal subtypes in EA tumors. In addition, increased expression of VEGF-activated genes together with elevated microvessel area determined by the AQUA method suggest that AA patients exhibit higher tumor vascularization. This study confirms the existence of distinct transcriptional programs in triple negative breast cancer in two separate cohorts and that these programs differ by racial group. Differences in TNBC subtypes and levels of tumor angiogenesis in AA versus EA patients

  10. Vitamin D and androgen receptor-targeted therapy for triple-negative breast cancer.

    PubMed

    Thakkar, A; Wang, B; Picon-Ruiz, M; Buchwald, P; Ince, Tan A

    2016-05-01

    Anti-estrogen and anti-HER2 treatments have been among the first and most successful examples of targeted therapy for breast cancer (BC). However, the treatment of triple-negative BC (TNBC) that lack estrogen receptor expression or HER2 amplification remains a major challenge. We previously discovered that approximately two-thirds of TNBCs express vitamin D receptor (VDR) and/or androgen receptor (AR) and hypothesized that TNBCs co-expressing AR and VDR (HR2-av TNBC) could be treated by targeting both of these hormone receptors. To evaluate the feasibility of VDR/AR-targeted therapy in TNBC, we characterized 15 different BC lines and identified 2 HR2-av TNBC lines and examined the changes in their phenotype, viability, and proliferation after VDR and AR-targeted treatment. Treatment of BC cell lines with VDR or AR agonists inhibited cell viability in a receptor-dependent manner, and their combination appeared to inhibit cell viability additively. Moreover, cell viability was further decreased when AR/VDR agonist hormones were combined with chemotherapeutic drugs. The mechanisms of inhibition by AR/VDR agonist hormones included cell cycle arrest and apoptosis in TNBC cell lines. In addition, AR/VDR agonist hormones induced differentiation and inhibited cancer stem cells (CSCs) measured by reduction in tumorsphere formation efficiency, high aldehyde dehydrogenase activity, and CSC markers. Surprisingly, we found that AR antagonists inhibited proliferation of most BC cell lines in an AR-independent manner, raising questions regarding their mechanism of action. In summary, AR/VDR-targeted agonist hormone therapy can inhibit HR2-av TNBC through multiple mechanisms in a receptor-dependent manner and can be combined with chemotherapy. PMID:27120467

  11. Clinical pilot study: efficacy of triple antibiotic therapy in Blastocystis positive irritable bowel syndrome patients

    PubMed Central

    2014-01-01

    Background Blastocystis species are common human enteric parasites. Carriage has been linked to Irritable Bowel Syndrome (IBS). Treatment of Blastocystis spp. with antimicrobials is problematic and insensitive diagnostic methods and re-infection complicate assessment of eradication. We investigated whether triple antibiotic therapy comprising diloxanide furoate, trimethoprim/sulfamethoxazole and secnidazole (TAB) given to diarrhoea-predominant IBS (D-IBS) patients positive for Blastocystis would achieve eradication. Methods In a longitudinal, prospective case study 10 D-IBS Blastocystis-positive patients took 14 days of diloxanide furoate 500 mg thrice daily, trimethoprim/sulfamethoxazole 160/80 mg twice daily and secnidazole 400 mg thrice daily. Faecal specimens were collected at baseline, day 15 and 4 weeks after completion of TAB. Specimens were analysed using faecal smear, culture and polymerase chain reaction (PCR) of the 16 SSU rRNA. Patients kept a concurrent clinical diary. Results Six (60%) patients cleared Blastocystis spp. after TAB, including three who had failed previous therapy. Subtypes detected were ST3 (60%), ST4 (40%), ST1 (20%) and ST7, 8 (10%); four patients had mixed ST infections. Serum immunoglobulin A (IgA) levels were low in 40% of patients. Higher rates of Blastocystis clearance were observed in patients symptomatic for less than a year (Mann–Whitney, p = 0.032, 95% confidence) with no associations found with age, previous antibiotic therapy, faecal parasite load, ST, IgA level or clinical improvement. Conclusions Clearance of Blastocystis spp. was achieved with TAB in 60% of D-IBS patients, an improvement over conventional monotherapy. Higher clearance rates are needed to facilitate investigation of the relevance of this parasite in clinically heterogenous IBS. PMID:25349629

  12. A case report: antiviral triple therapy with telaprevir in a haemodialysed HCV patient in Turkey.

    PubMed

    Akhan, S; Sayan, M; Sargin Altunok, E; Aynioglu, A

    2015-12-01

    A 49-year-old woman was diagnosed with chronic hepatitis C 7 years ago. She began haemodialysis at the same time. She was on the waiting list for kidney transplantation (KTx). The real-time PCR technique revealed an HCV RNA viral load of 212,000 IU/ml, genotype 1a, IL28B the rs12979860 minor allele heterozygous CT (rs8099917 TT homozygous). She had a history of first antiviral treatment for 48 weeks of PEG-IFN-alpha 2a, 135 μg/week in 2011, but the HCV infection relapsed. Considering her relatively young age, candidacy for renal transplant, and the heterozygous pattern of IL28B, we decided to proceed with a second (and last) antiviral treatment using triple therapy with telaprevir at the regular dose of 750 mg every 8 hours+PEG-IFN-alpha 2a 135 μg/week sc+200 mg RBV three times a week. At the end of 6-month therapy, HCV RNA was found to be negative at months 3, 5, and 6.The patient has reached the sustained virological response (SVR) and is ready for KTx. All renal transplant candidates (dialysis-dependent, or not) with HCV should be assessed for antiviral treatment given the increased risk of progressive liver disease due to immunosuppressive therapy, increased life expectancy compared to other HCV-positive patients on dialysis, and the inability to receive interferon after transplantation. PMID:26790555

  13. Simultaneous determination of triple therapy for Helicobacter pylori in human plasma by reversed phase chromatography with online wavelength switching

    NASA Astrophysics Data System (ADS)

    Ahmed, Sameh; Atia, Noha N.

    2015-02-01

    The infection of gastric mucosa by Helicobacter pylori (HP) is an essential cofactor in the aetiology of gastroduodenal ulcer and gastric carcinoma. Because of the bacterial resistance, combination therapy containing omeprazole (OME), tinidazole (TNZ) and clarithromycin (CLA) is commonly used for eradication of HP. However, the simultaneous determination of the triple therapy in human plasma was not reported. A simple, reproducible, and selective HPLC method was developed for the simultaneous determination of the triple therapy mixture used for management of HP infections in human plasma. An HPLC procedure based on a liquid-liquid extraction, enrichment of the analytes and subsequent reversed-phase chromatography with UV detection was used. To enable sensitive and selective detection, the method involved the use of online wavelength switching detection, with two different detection wavelengths; 280 nm for detection of OME and TNZ and 210 nm for detection of CLA. Separations were performed on C18 analytical column with acetonitrile-10 mM phosphate buffer of pH = 3.0 at flow rate of 1.0 mL min-1. The linear ranges in human plasma were 0.05-10 μg mL-1 with correlation coefficients >0.9990. The detection limits in human plasma were 0.02-0.07 μg mL-1. Validation parameters were assessed in compliance with US-FDA guidelines. The method proved to be valuable for the therapeutic drug monitoring after oral administration of triple therapy tablets.

  14. Simultaneous determination of triple therapy for Helicobacter pylori in human plasma by reversed phase chromatography with online wavelength switching.

    PubMed

    Ahmed, Sameh; Atia, Noha N

    2015-02-01

    The infection of gastric mucosa by Helicobacter pylori (HP) is an essential cofactor in the aetiology of gastroduodenal ulcer and gastric carcinoma. Because of the bacterial resistance, combination therapy containing omeprazole (OME), tinidazole (TNZ) and clarithromycin (CLA) is commonly used for eradication of HP. However, the simultaneous determination of the triple therapy in human plasma was not reported. A simple, reproducible, and selective HPLC method was developed for the simultaneous determination of the triple therapy mixture used for management of HP infections in human plasma. An HPLC procedure based on a liquid-liquid extraction, enrichment of the analytes and subsequent reversed-phase chromatography with UV detection was used. To enable sensitive and selective detection, the method involved the use of online wavelength switching detection, with two different detection wavelengths; 280nm for detection of OME and TNZ and 210nm for detection of CLA. Separations were performed on C18 analytical column with acetonitrile-10mM phosphate buffer of pH=3.0 at flow rate of 1.0mLmin(-1). The linear ranges in human plasma were 0.05-10μgmL(-1) with correlation coefficients >0.9990. The detection limits in human plasma were 0.02-0.07μgmL(-1). Validation parameters were assessed in compliance with US-FDA guidelines. The method proved to be valuable for the therapeutic drug monitoring after oral administration of triple therapy tablets. PMID:25459696

  15. Triple-drug therapy and return to work: results of a Quebec survey.

    PubMed

    Jalbert, Y

    Recent Quebec and Canadian statistics show the death rate declining among people living with HIV/AIDS. Triple-drug therapy has been shown to increase life expectancy and overall health. In the United States, a study of 55 people in Chicago living with HIV/AIDS found that 82 percent of them had considered returning to work. Another U.S. study showed that half the respondents had disclosed their sexual orientation to their employer. A survey questionnaire was prepared and distributed throughout the AIDS service organizations (ASOs) network and in two gay publications to see if the Canadian population has similar figures. The results showed that respondents under 45 years of age were more likely to want to return to work. Other conclusions of the study were that people with HIV/AIDS are not necessarily secure in their jobs, that the state of their health is their major area of concern, and that most people with HIV/AIDS do not want to return to their former jobs because of stress, discrimination, or their employer's attitude. The obligation for employers to make reasonable accommodations is a difficult concept for the employers to understand, and patients have concerns with explaining long or frequent absences from the workforce on their resumes. In 1998, the questionnaire will be distributed throughout the health and social services network. Ordering information is included. PMID:11365280

  16. Enriched transcription factor signatures in triple negative breast cancer indicates possible targeted therapies with existing drugs

    PubMed Central

    Willis, Scooter; De, Pradip; Dey, Nandini; Long, Bradley; Young, Brandon; Sparano, Joseph A.; Wang, Victoria; Davidson, Nancy E.; Leyland-Jones, Brian R.

    2015-01-01

    Purpose Triple negative (TN) breast cancers which lack expression of the estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) receptors convey a poor prognosis due in part to a lack of targeted therapies. Methods To identify viable targets for the treatment of TN disease, we have conducted a gene set enrichment analysis (GSEA) on seven different breast cancer whole genome gene expression cohorts comparing TN vs. ER + HER2 − to identify consistently enriched genes that share a common promoter motif. The seven cohorts were profiled on three different genome expression platforms (Affymetrix, Illumina and RNAseq) consisting in total of 2088 samples with IHC metadata. Results GSEA identified enriched gene expression patterns in TN samples that share common promoter motifs associated with SOX9, E2F1, HIF1A, HMGA1, MYC BACH2, CEBPB, and GCNF/NR6A1. Unexpectedly, NR6A1 an orphan nuclear receptor normally expressed in germ cells of gonads is highly expressed in TN and ER + HER2 − samples making it an ideal drug target. Conclusion With the increasing number of large sample size breast cancer cohorts, an exploratory analysis of genes that are consistently enriched in TN sharing common promoter motifs allows for the identification of possible therapeutic targets with extensive validation in patient derived data sets. PMID:26005638

  17. Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype?

    PubMed Central

    Le Du, Fanny; Eckhardt, Bedrich L.; Lim, Bora; Litton, Jennifer K.; Moulder, Stacy; Meric-Bernstam, Funda; Gonzalez-Angulo, Ana M.; Ueno, Naoto T.

    2015-01-01

    Significant research has been conducted to better understand the extensive, heterogeneous molecular features of triple-negative breast cancer (TNBC). We reviewed published TNBC molecular classifications to identify major groupings that have potential for clinical trial development. With the ultimate aim to streamline translational medicine, we linked these categories of TNBC according to their gene-expression signatures, biological function, and clinical outcome. To this end, we define five potential clinically actionable groupings of TNBC: 1) basal-like TNBC with DNA-repair deficiency or growth factor pathways; 2) mesenchymal-like TNBC with epithelial-to-mesenchymal transition and cancer stem cell features; 3) immune-associated TNBC; 4) luminal/apocrine TNBC with androgen-receptor overexpression; and 5) HER2-enriched TNBC. For each defined subtype, we highlight the major biological pathways and discuss potential targeted therapies in TNBC that might abrogate disease progression. However, many of these potential targets need clinical validation by clinical trials. We have yet to know how we can enrich the targets by molecular classifications. PMID:25973541

  18. Analysis of renal function during telaprevir-based triple therapy for chronic hepatitis C

    PubMed Central

    KOHJIMA, MOTOYUKI; KUROKAWA, MIHO; ENJOJI, MUNECHIKA; YOSHIMOTO, TSUYOSHI; NAKAMURA, TSUKASA; OHASHI, TOMOKO; FUKUIZUMI, KUNITAKA; HARADA, NAOHIKO; MURATA, YUSUKE; MATSUNAGA, KAZUHISA; KATO, MASAKI; KOTOH, KAZUHIRO; NAKAMUTA, MAKOTO

    2016-01-01

    Telaprevir (TVR) is used for the treatment of chronic hepatitis C in a combination therapy with pegylated-interferon and ribavirin. Although renal dysfunction is one of the critical adverse outcomes of this treatment, little is known regarding the mechanism of its onset. The present study assessed the association of renal function with TVR dose and viral response. Hematological, biochemical, urinary and virological parameters of renal function were examined during the TVR-based triple therapy of patients infected with hepatitis C virus (HCV) genotype 1b. Serum creatinine levels were increased and the estimated glomerular filtration rate (eGFR) was decreased in every patient during TVR administration, but these values recovered to normal levels following cessation of TVR. Fractional excretion of sodium was <1% at days 3 and 7, appearing similar regardless of baseline renal function. Urinary β2-microglobulin levels were elevated and were significantly higher in patients with renal dysfunction, as compared with those not exhibiting renal dysfunction (P<0.05). The reduction in renal function was milder in patients treated with a reduced TVR dose, and these patients had a significantly lower risk of developing renal dysfunction (P<0.05). Using a multivariate analysis, TVR dose and eGFR at the initiation of treatment were identified as significant contributory factors in the development of renal dysfunction. Reduction in TVR dose did not lead to a significant increase in the viral kinetics of HCV or detrimental effects on the sustained viral response (SVR) rate. It is hypothesized that renal dysfunction during TVR treatment is caused by damage of the renal tubule, in addition to pre-renal dysfunction, and that reduction in TVR dose reduces the rate of renal dysfunction without causing a significant decrease in the SVR rate. PMID:27168803

  19. Impact of Triple Therapy in Elderly Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Sambola, Antonia; Mutuberría, Maria; García del Blanco, Bruno; Alonso, Albert; Barrabés, José A.; Bueno, Héctor; Alfonso, Fernando; Cequier, Angel; Zueco, Javier; Rodríguez-Leor, Oriol; Tornos, Pilar; García-Dorado, David

    2016-01-01

    Background and Purpose Selecting an ideal antithrombotic therapy for elderly patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) can be challenging since they have a higher thromboembolic and bleeding risk than younger patients. The current study aimed to assess the efficacy and safety of triple therapy (TT: oral anticoagulation plus dual antiplatelet therapy: aspirin plus clopidogrel) in patients ≥75 years of age with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Methods A prospective multicenter study was conducted from 2003 to 2012 at 6 Spanish teaching hospitals. A cohort study of consecutive patients with AF undergoing PCI and treated with TT or dual antiplatelet therapy (DAPT) was analyzed. All outcomes were evaluated at 1-year of follow-up. Results Five hundred and eighty-five patients, 289 (49%) of whom were ≥75 years of age (79.6±3.4 years; 33% women) were identified. TT was prescribed in 55.9% of patients at discharge who had a higher thromboembolic risk (CHA2DS2VASc score: 4.23±1.51 vs 3.76±1.40, p = 0.007 and a higher bleeding risk (HAS-BLED ≥3: 88.6% vs 79.2%, p = 0.02) than those on DAPT. Therefore, patients on TT had a lower rate of thromboembolism than those on DAPT (0.6% vs 6.9%, p = 0.004; HR 0.08, 95% CI: 0.01–0.70, p = 0.004). Major bleeding events occurred more frequently in patients on TT than in those on DAPT (11.7% vs 2.4%, p = 0.002; HR 5.2, 95% CI: 1.53–17.57, p = 0.008). The overall mortality rate was similar in both treatment groups (11.9% vs 13.9%, p = 0.38); however, after adjustment for confounding variables, TT was associated with a reduced mortality rate (HR 0.33, 95% CI: 0.12–0.86, p = 0.02). Conclusions In elderly patients with AF undergoing PCI, the use of TT compared to DAPT was associated with reduced thromboembolism and mortality rates, although a higher rate of major bleeding. PMID:26808678

  20. Probiotics improve efficacy and tolerability of triple therapy to eradicate Helicobacter pylori: a meta-analysis of randomized controlled trials

    PubMed Central

    Gong, Yi; Li, Yan; Sun, Qian

    2015-01-01

    Objective: Gastric colonization by Helicobacter pylori is linked to a host of diseases, but eradication rates have declined in recent years. Some experimental studies suggest that probiotics may inhibit growth of H. pylori. This investigation was conducted to assess the impact of probiotics on both efficacy and tolerability of triple therapy to eradicate H. pylori. Methods: PubMed, Web of Science, and the Cochrane Collaboration were searched for relevant articles published through August 31, 2014. All analytics relied on commercially available software (Stata 11). Results: Twenty-three studies (N = 3900) qualified for meta-analysis. Pooled H. pylori eradication rates for triple therapy used alone and with added probiotics were 1464/2026 (72.26%; 95% CI, 67.66%-74.13) and 1513/1874 (80.74%; 95% CI, 74.68%-82.76%), respectively (odds ratio [OR] = 0.58; 95% CI, 0.50-0.68). Loss of appetite was similar in both groups (OR = 0.94; 95% CI, 0.61-1.45), but most adverse events (nausea, diarrhea, epigastric pain, vomiting, taste distortion, and skin rash) were mitigated through addition of probiotics. Publication bias was not evident, as indicated by Begg’s and Egger’s tests. Conclusions: Probiotics may improve the efficacy of triple therapy in eradicating gastric H. pylori and alleviate most treatment-related adverse events. PMID:26131283

  1. A Comparison between Hybrid Therapy and Standard Triple Therapy for Helicobacter pylori Eradication in Patients with Uremia: A Randomized Clinical Trial.

    PubMed

    Makhlough, Atieh; Fakheri, Hafez; Hojati, Samaneh; Hosseini, Vahid; Bari, Zohreh

    2016-01-01

    BACKGROUND The prevalence of peptic ulcer disease in hemodialysis patients is more than the general population. They are also more prone to complications including upper gastrointestinal bleeding. The aim of this study was to compare the efficacy of 14 days hybrid regimen with 14 days triple therapy for Helicobacter pylori (H. pylori ) eradication in hemodialysis patients. METHODS Forty hemodialysis patients with naïve H.pylori infection were randomized to receive either hybrid regimen (pantoprazole 40 mg + amoxicillin 500 mg, both twice a day during the first 7 days, followed by pantoprazole 40 mg + amoxicillin 500 mg + clarithromycin 500 mg + tinidazole 500 mg, all twice a day, for the second 7 days, or standard triple therapy including pantoprazole 40 mg, clarithromycin 500 mg, and amoxicillin 500 mg, all twice a day for 14 days. H.pylori eradication was assessed by fecal H.pylori antigen test 8 weeks after the treatment. RESULTS All the patients completed the study. According to both intention to treat and per-protocol analyses, H.pylori eradication rates were 100% (95% confidence interval (CI): 100) in those who received hybrid therapy and 70% (95% CI: 69.4 - 70.8) in those who were treated by standard triple therapy (p=0.02). Severe adverse effects were not reported by any patient; however, mild adverse effects were more frequent in those who received standard triple therapy (p<0.05). CONCLUSION Hybrid regimen could achieve ideal H.pylori eradication rates with low rates of adverse effects. PMID:26933480

  2. Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: possible implications for targeted therapy

    PubMed Central

    2011-01-01

    Introduction Triple negative breast cancer is associated with poorer prognosis and unresponsiveness to endocrine and anti-HER2 directed agents. Despite emerging data supporting the use of polyADP-ribose polymerase (PARP) inhibitors, complete and durable responses are rare and exploration of additional targeted therapies is needed. Epidermal growth factor receptor (EGFR) is expressed in triple negative breast cancer and several clinical trials are testing the role of anti-EGFR directed therapy. However, the rate of EGFR mutations is poorly defined. We, therefore, sought to characterize EGFR mutations in triple negative breast cancers. Methods Seventy samples were randomly chosen from a cohort of 653 triple negative breast tumours for EGFR mutation analysis. These samples were immunostained for EGFR protein expression and consisted of negatively stained and positively stained cases. DNA was extracted from paraffin blocks and polymerase chain reaction was performed to amplify exon regions 18 to 21 of the EGFR gene. Direct sequencing of the purified PCR products was performed. Results EGFR mutations were found in 8 of 70 samples (11.4%). Mutations were predominantly exon 19 deletions (4 of 70 samples, 5.7%), which clustered in the region spanning codons 746 to 759 within the kinase domain of EGFR. Two types of exon 19 deletions were seen: a 15 nucleotide deletion (del E746-A750) (2 of 70 samples) and a 24 nucleotide deletion (del S752 - I759) (2 of 70 samples). Other exon 19 mutations observed were the inversion of the complementary strand (1 of 70 samples). Exon 21 mutations included missense substitution, L858R (1 of 70 samples) and T847I (2 of 70 samples). Mutations observed were independent of EGFR protein expression determined by immunohistochemical staining. Conclusions This study is among the first to document the presence and estimate the prevalence of EGFR mutations in triple negative breast cancer. These findings have potential implications for the design of

  3. Increased Ribavirin Bioavailability Associated With Telaprevir Use in Hepatitis C Patients Treated With PEGylated -Interferon/Ribavirin/Telaprevir Triple Therapy

    PubMed Central

    Pradat, Pierre; Virlogeux, Victor; Maynard, Marianne; Leclercq, Mathilde; Hatu, Giorgiana; Amiri, Majid; Lebosse, Fanny; Miailhes, Patrick; Zoulim, Fabien; Gagnieu, Marie-Claude; Bailly, François

    2015-01-01

    Background: Anemia is more frequent in patients receiving telaprevir with PEGylated interferon/ribavirin (PEG-IFN/RBV) than in those receiving PEG-IFN/RBV alone. Objectives: The objective was to measure the impact of telaprevir on RBV bioavailability and to assess the concomitant renal function. Materials and Methods: Thirty-seven hepatitis C virus (HCV) patients non-responders to a previous course of PEG-IFN/RBV therapy and re-treated with triple therapy combining PEG-IFN/RBV and telaprevir were analyzed. RBV bioavailability was measured before the triple therapy initiation, during telaprevir treatment at week (W) 4 and W8, and after telaprevir cessation (post W16). The renal function was assessed by estimating the glomerular filtration rate (eGFR). Results: At W4, RBV bioavailability, expressed as mg/L/daily dose/kg body weight, was significantly increased (median increase = 0.06 mg/L/dose/kg; P < 0.001). In parallel, the renal function was impaired with a mean eGFR decrease of -6.8 mL/minutes/1.73 m² (P = 0.109). Between W4 and W8, RBV bioavailability continued to increase (P < 0.001) but subsequently decreased slightly after telaprevir discontinuation with a concomitant restoration of the renal function (eGFR increase of 6.34 mL/minutes/1.73 m²). Conclusions: Our results indicated a reversible increase in RBV bioavailability after telaprevir exposure, which might be linked to the impairment of the GFR. This also suggests a RBV-telaprevir pharmacological interaction, a possible source of severe anemia observed under triple therapy. These results suggest that RBV pharmacological monitoring may be clinically relevant, especially in the context of first-generation HCV protease inhibitor-based therapy. PMID:26500683

  4. Comparison of Azithromycin and Clarithromycin Triple Therapy Regimens for Helicobacter Pylori Eradication in Hemodialysis Patients

    PubMed Central

    Jalalzadeh, Mojgan; Nazarian, Morteza; Vafaeimanesh, Jamshid; Mirzamohammadi, Fatemeh

    2012-01-01

    Background Helicobacter pylori eradication with clarithromycin is more expensive than with azithromycin. Objectives This study aimed to compare the effectiveness of these two antibiotics in eradicating H. pylori in hemodialysis (HD) patients. Patients and Methods This is a prospective, randomized, double-blinded clinical trial analysis of HD patients. Patients who had dyspepsia and showed positive results for two of three tests, anti-H. pylori serology, H. pylori stool antigen (HpSAg), or Urease Breath Test (UBT), were included in the study. The subjects consisted of 39 dialysis patients who were randomly divided into two groups that received medication twice daily. Group OAC received 20 mg omeprazol, 500 mg amoxycilin, and 250 mg clarithromycin, and Group OAAz received 20 mg omeprazol, 500 mg amoxicillin, and 250 mg azithromycin. Both regimens were administered for 14 days. Eradication was investigated by performing the UBT and the HpSAg test eight weeks later. Results This study began with 39 patients, 37 of which completed the treatment schedule (20 males and 17 females, mean age 59 years). Two patients died due to MI before beginning treatment. In the OAC group, negative results on the UBT and HpSAg tests were found in 82.4% and 88.2% of the participants, respectively. In the OAAz group, these values were 80% and 85%, respectively. The data showed that the difference between the two regimens was not significant (P = 1.0). Conclusions According to the data, no differences in eradication rates were apparent between the azitromycin and the claritromycin regimens. However, lower cost and fewer complaints could be considered as an advantage of the triple therapy with azithromycin. PMID:23573488

  5. Tyrosine triple mutated AAV2-BDNF gene therapy in a rat model of transient IOP elevation

    PubMed Central

    Igarashi, Tsutomu; Kobayashi, Maika; Kameya, Shuhei; Fujimoto, Chiaki; Nakamoto, Kenji; Takahashi, Hisatomo; Igarashi, Toru; Miyake, Noriko; Iijima, Osamu; Hirai, Yukihiko; Shimada, Takashi; Okada, Takashi; Takahashi, Hiroshi

    2016-01-01

    Purpose We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), which provides protection to retinal ganglion cells (RGCs) in rodents, in a model of transient intraocular pressure (IOP) elevation using a mutant (triple Y-F) self-complementary adeno-associated virus type 2 vector encoding BDNF (tm-scAAV2-BDNF). Methods The tm-scAAV2-BDNF or control vector encoding green fluorescent protein (GFP; tm-scAAV2-GFP) was intravitreally administered to rats, which were then divided into four groups: control, ischemia/reperfusion (I/R) injury only, I/R injury with tm-scAAV2-GFP, and tm-scAAV2-BDNF. I/R injury was then induced by transiently increasing IOP, after which the rats were euthanized to measure the inner retinal thickness and cell counts in the RGC layer. Results Intravitreous injection of tm-scAAV2-BDNF resulted in high levels of BDNF expression in the neural retina. Histological analysis showed that the inner retinal thickness and cell numbers in the RGC layer were preserved after transient IOP elevation in eyes treated with tm-scAAV2-BDNF but not in the other I/R groups. Significantly reduced glial fibrillary acidic protein (GFAP) immunostaining after I/R injury in the rats that received tm-scAAV2-BDNF indicated reduced retinal stress, and electroretinogram (ERG) analysis confirmed preservation of retinal function in the tm-scAAV2-BDNF group. Conclusions These results demonstrate the feasibility and effectiveness of neuroprotective gene therapy using tm-scAAV2-BDNF to protect the inner retina from transiently high intraocular pressure. An in vivo gene therapeutic approach to the clinical management of retinal diseases in conditions such as glaucoma, retinal artery occlusion, hypertensive retinopathy, and diabetic retinopathy thus appears feasible. PMID:27440998

  6. Monitoring the Antioxidant Mediated Chemosensitization and ARE-Signaling in Triple Negative Breast Cancer Therapy

    PubMed Central

    Foygel, Kira; Sekar, Thillai V.; Paulmurugan, Ramasamy

    2015-01-01

    Chemotherapy often fails due to cellular detoxifying mechanisms, including phase-II enzymes. Activation of Nrf2-Keap1 pathway induces phase-II enzymes expression through ARE-signaling and prevents cancer development. Nrf2-overexpression in cancer cells results in chemo- and/or radioresistance. This necessitates understanding of Nrf2-regulation, and identification of Nrf2 activators/inhibitors sensitizing cancer cells to improve chemotherapy. N-terminal 435-amino acids of Nrf2 are crucial for Keap1 binding during ubiquitination. Identification of a minimum Nrf2-domain required for Keap1 binding without altering endogenous ARE-signaling would be a novel tool to study Nrf2-signaling. Current study developed firefly-luciferase reporter fusion with N-terminal Nrf2-domain of different lengths and examined its response to Nrf2-activators in cells. The results identified FLuc2 fusion with N-terminal 100-aa of Nrf2 is sufficient for measuring Nrf2-activation in cancer cells. We used MDA-MB231 cells expressing this particular construct for studying antioxidant induced Nrf2-activation and chemosensitization in triple-negative breast cancer therapy. While antioxidant EGCG showed chemosensitization of MDA-MB231 cells to cisplatin by activating Nrf2-ARE signaling, PTS, another antioxidant showed chemoprotection. Tumor xenograft study in mouse demonstrates that combinational treatment by cisplatin/EGCG resulted in tumor growth reduction, compared to cisplatin alone treatment. The results of this study highlight the importance of identifying selective combination of antioxidants/chemotherapeutic agents for customized treatment strategy. PMID:26536456

  7. Furazolidone-based triple and quadruple eradication therapy for Helicobacter pylori infection

    PubMed Central

    Xie, Yong; Zhu, Yin; Zhou, Hong; Lu, Zhi-Fa; Yang, Zhen; Shu, Xu; Guo, Xiao-Bai; Fan, Hui-Zhen; Tang, Jian-Hua; Zeng, Xue-Ping; Wen, Jian-Bo; Li, Xiao-Qing; He, Xing-Xing; Ma, Jiu-Hong; Liu, Dong-Sheng; Huang, Cai-Bin; Xu, Ning-Jian; Wang, Nong-Rong; Lu, Nong-Hua

    2014-01-01

    AIM: To evaluate the efficacy of furazolidone-based triple and quadruple therapy in eradicating Helicobacter pylori (H. pylori) in a multi-center randomized controlled trial. METHODS: A total of 720 H. pylori positive patients with duodenal ulcer disease were enrolled at 10 different hospitals in Jiangxi province in China. The patients were randomly assigned to four treatment groups as follows: patients in Groups 1 and 3 received rabeprazole (10 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively; patients in Groups 2 and 4 received rabeprazole (10 mg), bismuth (220 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively. The primary outcome measure was H. pylori eradication rate 4 wk after treatment by intention-to-treat and per protocol analysis, while the secondary outcome measures were symptom and sign changes at the end of treatment and 4 wk after the end of treatment, as well as the proportion of patients who developed adverse events. RESULTS: The demographic data of the four groups were not significantly different. Overall, 666 patients completed the scheme and were re-assessed with the 13C-urea breath test. The intention-to-treat analysis of the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 74.44%, 82.78%, 78.89% and 86.11%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. According to the per protocol analysis, the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 81.21%, 89.22%, 85.54% and 92.26%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. The number of adverse events was 15 (8.3%), 16 (8.9%), 15 (8.3%) and 17 (9.4%) in Groups 1, 2, 3 and 4, respectively, including dizziness, vomiting, diarrhea, nausea, skin rash, itchy skin, and malaise. The symptoms were relieved without special treatment in all of the patients. CONCLUSION: Both 7- and 10-d

  8. Economic evaluation of a single-pill triple antihypertensive therapy with valsartan, amlodipine, and hydrochlorothiazide against its dual components.

    PubMed

    Stafylas, Panagiotis; Kourlaba, Georgia; Hatzikou, Magda; Georgiopoulos, Dimitrios; Sarafidis, Pantelis; Maniadakis, Nikolaos

    2015-01-01

    The aim of this study was to compare the cost-utility of the first available single-pill triple combination antihypertensive therapy containing valsartan (V), amlodipine (A) and hydrochlorothiazide (H), with each of the same components dual combinations in patients with moderate to severe hypertension. A Markov model with eight health states was constructed. The short-term effect of antihypertensive treatment on blood pressure was extrapolated through the Hellenic SCORE and Framingham risk equations, estimating the long-term survival and quality-adjusted life-years (QALYs) saved. Costs and outcomes were evaluated over lifetime, divided into annual cycles and discounted at 3.0 % with 2013 as reference year. The analysis was conducted by the Greek third-party-payer perspective. The triple combination treatment cost was estimated at €16,525 compared to €15,480 for V/A, €14,125 for V/H and €11,690 for A/H. The QALYs saved with the triple combination were 12.76 vs. 12.64, 12.61 and 12.38 for double combinations respectively. The incremental cost-effectiveness ratio of the triple combination versus V/A and A/H was far lower than the Greek GDP per capita (€8,690/QALY and €12,695/QALY, respectively) and really close for V/H (€16,192/QALY), suggesting V/A/H combination to be cost-effective. Extensive sensitivity analyses confirmed the robustness of the results. The probability that the triple combination is cost effective was more than 90 % at a willingness-to-pay threshold of €18,000/QALY. This is the first study to evaluate the cost-utility of a single-pill triple combination. The single-pill V/A/H therapy is a cost-effective antihypertensive choice for the treatment of moderate to severe hypertension, compared to its dual components. PMID:26097434

  9. Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors.

    PubMed

    Ayala-Orozco, Ciceron; Urban, Cordula; Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-10-10

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100nm gold nanomatryushkas, comprising concentric gold-silica-gold layers compared to conventional ~150nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5× accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  10. Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

    PubMed Central

    Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-01-01

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  11. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients.

    PubMed

    Vafaeimanesh, Jamshid; Jalalzadeh, Mojgan; Nazarian, Morteza

    2014-01-01

    To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin) for the eradication of Helicobacter pylori in hemodialysis (HD) patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg) and urease breath test (UBT). The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years). Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0). The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients. PMID:24434382

  12. Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer

    NASA Astrophysics Data System (ADS)

    Park, Dongjin; Ahn, Kyung-Ohk; Jeong, Kyung-Chae; Choi, Yongdoo

    2016-05-01

    Here, we fabricated polypyrrole nanoparticles (PPys) (termed HA10-PPy, HA20-PPy, and HA40-PPy) doped with different average molecular weight hyaluronic acids (HAs) (10, 20, and 40 kDa, respectively), and evaluated the effect of molecular weight of doped HA on photothermal induction, fluorescence quenching, and drug loading efficiencies. Doxorubicin-loaded HA-doped PPys (DOX@HA-PPys) could be used for imaging and therapy of triple-negative breast cancer (TNBC). Fluorescence turn-on, stimuli-responsive drug release, and photo-induced heating of DOX@HA-PPys enabled not only activatable fluorescence imaging but also subsequent chemo/photothermal dual therapy for TNBC. In particular, we illustrated the potential usefulness of the photothermal effect of the nanoparticles for overcoming chemoresistance in TNBC.

  13. Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer.

    PubMed

    Park, Dongjin; Ahn, Kyung-Ohk; Jeong, Kyung-Chae; Choi, Yongdoo

    2016-05-01

    Here, we fabricated polypyrrole nanoparticles (PPys) (termed HA10-PPy, HA20-PPy, and HA40-PPy) doped with different average molecular weight hyaluronic acids (HAs) (10, 20, and 40 kDa, respectively), and evaluated the effect of molecular weight of doped HA on photothermal induction, fluorescence quenching, and drug loading efficiencies. Doxorubicin-loaded HA-doped PPys (DOX@HA-PPys) could be used for imaging and therapy of triple-negative breast cancer (TNBC). Fluorescence turn-on, stimuli-responsive drug release, and photo-induced heating of DOX@HA-PPys enabled not only activatable fluorescence imaging but also subsequent chemo/photothermal dual therapy for TNBC. In particular, we illustrated the potential usefulness of the photothermal effect of the nanoparticles for overcoming chemoresistance in TNBC. PMID:27004751

  14. Long-term follow up Helicobacter Pylori reinfection rate after second-line treatment: bismuth-containing quadruple therapy versus moxifloxacin-based triple therapy

    PubMed Central

    2013-01-01

    Background The increasing trend of antibiotic resistance requires effective second-line Helicobacter pylori (H. pylori) treatment in high prevalence area of H. pylori. The aim of our study was to evaluate the reinfection rate of H. pylori after second-line treatment that would determine the long-term follow up effect of the rescue therapy. Methods A total of 648 patients who had failed previous H. pylori eradication on standard triple therapy were randomized into two regimens: 1, esomeprazole (20 mg b.i.d), tripotassium dicitrate bismuthate (300 mg q.i.d), metronidazole (500 mg t.i.d), and tetracycline (500 mg q.i.d) (EBMT) or 2, moxifloxacin (400 mg q.d.), esomeprazole (20 mg b.i.d), and amoxicillin (1000 mg b.i.d.) (MEA). At four weeks after completion of eradication therapy, H. pylori tests were performed with 13C urea breath test or invasive tests. In patients who maintained continuous H. pylori negativity for the first year after eradication therapy, H. pylori status was assessed every year. For the evaluation of risk factors of reinfection, gender, age, clinical diagnosis, histological atrophic gastritis or intestinal metaplasia were analyzed. Results The recrudescence rate of the EBMT was 1.7% and of the MEA group 3.3% (p = 0.67). The annual reinfection rate of H. pylori of EBMT was found to be 4.45% and the MEA group 6.46%. Univariate analysis (Log-rank test) showed no association with any clinical risk factor for reinfection. Conclusions The long-term reinfection rate of H. pylori stayed low in both of bismuth-containing quadruple therapy and moxifloxacin-based triple therapy; thus reinfection cannot affect the choice of second-line treatment. Trial registration Clinical Trial Registration Number NCT01792700 PMID:24050512

  15. The Clinical and Bacteriological Factors for Optimal Levofloxacin-Containing Triple Therapy in Second-Line Helicobacter pylori Eradication

    PubMed Central

    Tai, Wei-Chen; Lee, Chen-Hsiang; Chiou, Shue-Shian; Kuo, Chung-Mou; Kuo, Chung-Huang; Liang, Chih-Ming; Lu, Lung-Sheng; Chiu, Chien-Hua; Wu, Keng-Liang; Chiu, Yi-Chun; Hu, Tsung-Hui; Chuah, Seng-Kee

    2014-01-01

    Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI] = 63.9–85.3%) and 90.5% (95% CI = 84.5–98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6–78.5%) and 84.8% (95% CI = 76.8–93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful

  16. Near infrared light-actuated gold nanorods with cisplatin-polypeptide wrapping for targeted therapy of triple negative breast cancer

    NASA Astrophysics Data System (ADS)

    Feng, Bing; Xu, Zhiai; Zhou, Fangyuan; Yu, Haijun; Sun, Qianqian; Wang, Dangge; Tang, Zhaohui; Yu, Haiyang; Yin, Qi; Zhang, Zhiwen; Li, Yaping

    2015-09-01

    Despite considerable progress being made in breast cancer therapy, the complete eradication of highly aggressive triple negative breast cancer (TNBC) remains a notable challenge today. We herein report on the fabrication of novel gold nanorods (GNRs) with covalent cisplatin-polypeptide wrapping and folic acid (FA) conjugation (FA-GNR@Pt) for the targeted photothermal (PT) therapy and chemotherapy of TNBC. The FA-GNR@Pt hybrid nanoparticles are designed to integrate the photothermal conversion property of GNRs, the superior biocompatibility of polypeptide poly(l-glutamic acid) (PGA), the chemotoxicity of cisplatin, and the tumor targeting ability of FA into one single nanoplatform. In combination with localized near infrared (NIR) laser illumination, the resulting FA-GNR@Pt hybrid nanoparticles are able to significantly inhibit the growth of the TNBC tumor when administered systemically. In particular, they can extensively suppress the dissemination of TNBC cells from the primary tumor to the lung by eliminating the peripheral tumor blood vessels. Collectively, our studies demonstrate that the combined PT therapy and chemotherapy using cisplatin-loaded GNRs with FA conjugation might imply a promising strategy for targeted treatment of TNBC.Despite considerable progress being made in breast cancer therapy, the complete eradication of highly aggressive triple negative breast cancer (TNBC) remains a notable challenge today. We herein report on the fabrication of novel gold nanorods (GNRs) with covalent cisplatin-polypeptide wrapping and folic acid (FA) conjugation (FA-GNR@Pt) for the targeted photothermal (PT) therapy and chemotherapy of TNBC. The FA-GNR@Pt hybrid nanoparticles are designed to integrate the photothermal conversion property of GNRs, the superior biocompatibility of polypeptide poly(l-glutamic acid) (PGA), the chemotoxicity of cisplatin, and the tumor targeting ability of FA into one single nanoplatform. In combination with localized near infrared (NIR

  17. Modified Sequential Therapy Regimen versus Conventional Triple Therapy for Helicobacter Pylori Eradication in Duodenal Ulcer Patients in China: A Multicenter Clinical Comparative Study.

    PubMed

    Zhou, Ying-Qun; Xu, Ling; Wang, Bing-Fang; Fan, Xiao-Ming; Wu, Jian-Ye; Wang, Chun-Yan; Guo, Chuan-Yong; Xu, Xuan-Fu

    2012-01-01

    Objective. Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. To observe the effect of eradicating Helicobacter pylori (H. pylori) and the treatment of duodenal ulcer by 2 kinds of modified sequential therapy through comparing with that of 10-day standard triple therapy. Methods. A total of 210 patients who were confirmed in duodenal ulcer active or heal period by gastroscopy and H. pylori positive confirmed by rapid urease test, serum anti-H. pylori antibody (ELASE), or histological examination enrolled in the study. All the patients were randomly divided into three groups: group A (70 cases) and group B (70 cases) were provided 10-day modified sequential therapy; group C (70 cases) was provided 10-day standard triple therapy. Patients of group A received 20 mg of Esomeprazole, 500 mg of Clarithromycin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group B received 20 mg of Esomeprazole, 1000 mg of Amoxicillin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group C received 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for standard 10-day therapy. All drugs were given twice daily. H. pylori eradication rate was checked four to eight weeks after taking the medicine by using a (13)C urea breath test. In the first, second, third, seventh, twenty-first, thirty-fifth days respectively, the symptoms of patients such as epigastric gnawing, burning pain, and acidity were evaluated simultaneously. Results. Overall, 210 patients accomplished all therapy schemes, 9 case patients were excluded. The examination result indicated that the H. pylori eradication rate of each group was as follows: group A 92.5% (62/67), group B 86.8% (59/68), and group C 78.8% (52/66). The H. pylori eradication rate of

  18. Ultrasensitive HCV RNA Quantification in Antiviral Triple Therapy: New Insight on Viral Clearance Dynamics and Treatment Outcome Predictors

    PubMed Central

    Garbuglia, Anna Rosa; Visco-Comandini, Ubaldo; Lionetti, Raffaella; Lapa, Daniele; Castiglione, Filippo; D’Offizi, Gianpiero; Taibi, Chiara; Montalbano, Marzia; Capobianchi, Maria Rosaria; Paci, Paola

    2016-01-01

    Objectives Identifying the predictive factors of Sustained Virological Response (SVR) represents an important challenge in new interferon-based DAA therapies. Here, we analyzed the kinetics of antiviral response associated with a triple drug regimen, and the association between negative residual viral load at different time points during treatment. Methods Twenty-three HCV genotype 1 (GT 1a n = 11; GT1b n = 12) infected patients were included in the study. Linear Discriminant Analysis (LDA) was used to establish possible association between HCV RNA values at days 1 and 4 from start of therapy and SVR. Principal component analysis (PCA) was applied to analyze the correlation between HCV RNA slope and SVR. A ultrasensitive (US) method was established to measure the residual HCV viral load in those samples which resulted “detected <12IU/ml” or undetectable with ABBOTT standard assay, and was retrospectively used on samples collected at different time points to establish its predictive power for SVR. Results According to LDA, there was no association between SVR and viral kinetics neither at time points earlier than 1 week (days 1 and 4) after therapy initiation nor later. The slopes were not relevant for classifying patients as SVR or no-SVR. No significant differences were observed in the median HCV RNA values at T0 among SVR and no-SVR patients. HCV RNA values with US protocol (LOD 1.2 IU/ml) after 1 month of therapy were considered; the area under the ROC curve was 0.70. Overall, PPV and NPV of undetectable HCV RNA with the US method for SVR was 100% and 46.7%, respectively; sensitivity and specificity were 38.4% and 100% respectively. Conclusion HCV RNA “not detected” by the US method after 1 month of treatment is predictive of SVR in first generation Protease inhibitor (PI)-based triple therapy. The US method could have clinical utility for advanced monitoring of virological response in new interferon based DAA combination regimens. PMID:27560794

  19. Two-Year Follow-Up Analysis of Telaprevir-Based Antiviral Triple Therapy for HCV Recurrence in Genotype 1 Infected Liver Graft Recipients as a First Step towards Modern HCV Therapy

    PubMed Central

    Neuhaus, Ruth; Eurich, Dennis; Hofmann, Jörg; Bayraktar, Sandra; Pratschke, Johann; Bahra, Marcus

    2016-01-01

    Objective. The introduction of protease inhibitors telaprevir and boceprevir in 2011 had extended the antiviral treatment options especially in genotype 1 infected hepatitis C relapsers and nonresponders to interferon/ribavirin therapy. The aim of this study was to analyze the long-term treatment efficiency of telaprevir-based triple therapy for patients with hepatitis C reinfection after orthotopic liver transplantation. Patients and Methods. We included 12 patients with histologically confirmed graft fibrosis due to hepatitis C reinfection. The treatment duration was scheduled as 12 weeks of telaprevir-based antiviral triple therapy followed by 36 weeks of dual therapy with pegylated interferon/ribavirin. The patients were followed up for two years after the end of triple therapy. Results. Of the 12 patients, 6 (50%) completed the full 48 weeks of antiviral treatment. An end of treatment response and a sustained virological response 52 weeks after the end of the antiviral treatment course were achieved in 8/12 (67%) and 7/12 (58%) patients, respectively. Conclusion. Telaprevir-based triple therapy was shown to be a long-term effective but complex treatment option for individual patients with hepatitis C graft. With the recent improvements in hepatitis C therapy options telaprevir may not be recommended as a standard therapy for this indication anymore. PMID:27195149

  20. Eradication of Helicobacter pylori in Children by Triple Therapy Regimens of Amoxicillin, Omeprazole, and Clarithromycin or Azithromycin

    PubMed Central

    Esmaeili-Dooki, Mohammad Reza; Shirdel, Hossein; Hajiahmadi, Mahmood

    2015-01-01

    Background and Objectives: The present study aimed to evaluate the effect of classical and azithromycin-containing triple therapy eradication regimen against H. Pylori in children, and to determine the level of patients’ tolerance. Patients and Methods: This single clinical trial was performed in 2014 on 2 to 15 years old children. All children, in whom H. Pylori infection was confirmed through multiple biopsies of the stomach and required treatment, were enrolled in the study. H. Pylori-positive patients were treated alternately with two different drug regimens; Group OCA received clarithromycin 7.5 mg/kg/day every 12 hours for 10 days, amoxicillin 50 mg/kg/day every 12 hours for 10 days, and omeprazole 1 mg/kg/day every 12 hours for two weeks, and Group OAA received azithromycin 10 mg/kg/day once a day (before meal) for 6 days along with amoxicillin and omeprazole. Four to six weeks after completion of treatment, patients’ stool was tested for H. Pylori through the monoclonal method using the Helicobacter antigen quick kit. Results: There were no significant differences between the two groups regarding gender and age of patients. Based on ITT analysis, the therapeutic response in the OAA and OCA groups were 56.2% and 62.5%, respectively (P = 0.40). Drug adverse effects were 15.6% in the OCA and 3.1% in the OAA group (P = 0.19). Conclusions: The therapeutic response was seen in more than half of the patients treated with triple therapy of H. Pylori eradication regimen including azithromycin or clarithromycin, and there was no significant difference between the two treatment groups. PMID:26635936

  1. A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients

    PubMed Central

    Braun, Dominique L.; Rauch, Andri; Aouri, Manel; Durisch, Nina; Eberhard, Nadia; Anagnostopoulos, Alexia; Ledergerber, Bruno; Müllhaupt, Beat; Metzner, Karin J.; Decosterd, Laurent; Böni, Jürg; Weber, Rainer; Fehr, Jan

    2015-01-01

    Background The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV) infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR) using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group. Methodology Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir) for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin. Results We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR) HCV-RNA decline after silibinin therapy was 2.65 (2.1–2.8) log10 copies/mL. Fifteen of sixteen patients (94%) had undetectable HCV RNA at weeks 4 and 12, eleven patients (69%) showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48), and ten patients (63%) reached SVR at week 12 (SVR 12). Six of the sixteen patients (37%) did not reach SVR 12: One patient had rapid virologic response (RVR) (i.e., undetectable HCV-RNA at week 4) but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete

  2. The efficacy of blueberry and grape seed extract combination on triple therapy for Helicobacter pylori eradication: a randomised controlled trial.

    PubMed

    Chua, Chian-Sem; Yang, Kuo-Ching; Chen, Jui-Hao; Liu, Yuh-Hwa; Hsu, Yi-Hsin; Lee, Hsiu-Chuan; Huang, Shih-Yi

    2016-03-01

    Helicobacter pylori is a major risk factor for gastritis, gastric ulcers and gastric cancer. Traditional therapy with proton pump inhibitor and antibiotics is regarded as optimal for H. pylori eradication whereas, the eradication rate is unsatisfactory. Studies have reported that cranberry may inhibit H. pylori adhesion to the human gastric mucus but lack of other berry extracts have been evaluated in clinical study. Thus, a 9-week add-on randomised controlled trial was conducted to explore the impact of blueberry and grape seed extract (BGE) combinations traditional therapy for H. pylori eradication. In results, we found that there was no significant difference of eradication rate between the berry extract group and placebo group in the intention-to-treat analysis and in the per-protocol analysis (94.64% versus 84.62%, p = 0.085). Diarrhoea, constipation and epigastric pain were observed increasing during ingestion of the berry extract in some cases. In conclusion, this study indicated that no significant difference existed between the BGE extract group and placebo group in eradication rate under triple therapy. PMID:26883189

  3. Dual targeted therapy with p53 siRNA and Epigallocatechingallate in a triple negative breast cancer cell model.

    PubMed

    Braicu, Cornelia; Pileczki, Valentina; Pop, Laura; Petric, Roxana Cojocneanu; Chira, Sergiu; Pointiere, Eve; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

    2015-01-01

    Triple-negative breast cancer (TNBC) is a highly aggressive phenotype that is resistant to standard therapy. Thus, the development of alternative therapeutic strategies for TNBC is essential. The purpose of our in vitro study was to evaluate the impact of p53 gene silencing in conjunction with the administration of a natural compound, epigallocatechingallate (EGCG). RT2Profiler PCR Array technology was used to evaluate the impact of dual treatment on the main genes involved in apoptosis in the Hs578T cell culture model of TNBC. Gene expression analysis revealed 28 genes were significantly altered (16 upregulated and 12 downregulated) in response to combined p53 siRNA and EGCG treatment. Further analysis revealed that p53 siRNA and EGCG dual therapy leads to the activation of pro-apoptotic genes and the inhibition of pro-survival genes, autophagy, and cell network formation. These results indicate that this dual therapy targets both the apoptotic and angiogenic pathways, which may improve treatment effectiveness for tumors resistant to conventional treatment. PMID:25849487

  4. Near infrared light-actuated gold nanorods with cisplatin-polypeptide wrapping for targeted therapy of triple negative breast cancer.

    PubMed

    Feng, Bing; Xu, Zhiai; Zhou, Fangyuan; Yu, Haijun; Sun, Qianqian; Wang, Dangge; Tang, Zhaohui; Yu, Haiyang; Yin, Qi; Zhang, Zhiwen; Li, Yaping

    2015-09-28

    Despite considerable progress being made in breast cancer therapy, the complete eradication of highly aggressive triple negative breast cancer (TNBC) remains a notable challenge today. We herein report on the fabrication of novel gold nanorods (GNRs) with covalent cisplatin-polypeptide wrapping and folic acid (FA) conjugation (FA-GNR@Pt) for the targeted photothermal (PT) therapy and chemotherapy of TNBC. The FA-GNR@Pt hybrid nanoparticles are designed to integrate the photothermal conversion property of GNRs, the superior biocompatibility of polypeptide poly(l-glutamic acid) (PGA), the chemotoxicity of cisplatin, and the tumor targeting ability of FA into one single nanoplatform. In combination with localized near infrared (NIR) laser illumination, the resulting FA-GNR@Pt hybrid nanoparticles are able to significantly inhibit the growth of the TNBC tumor when administered systemically. In particular, they can extensively suppress the dissemination of TNBC cells from the primary tumor to the lung by eliminating the peripheral tumor blood vessels. Collectively, our studies demonstrate that the combined PT therapy and chemotherapy using cisplatin-loaded GNRs with FA conjugation might imply a promising strategy for targeted treatment of TNBC. PMID:26222373

  5. Behavioral Outcomes of Parent-Child Interaction Therapy and Triple P-Positive Parenting Program: A Review and Meta-Analysis

    ERIC Educational Resources Information Center

    Thomas, Rae; Zimmer-Gembeck, Melanie

    2007-01-01

    We conducted a review and meta-analyses of 24 studies to evaluate and compare the outcomes of two widely disseminated parenting interventions--Parent-Child Interaction Therapy and Triple P-Positive Parenting Program. Participants in all studies were caregivers and 3- to 12-year-old children. In general, our analyses revealed positive effects of…

  6. Neoadjuvant Therapy in Operable Breast Cancer: Application to Triple Negative Breast Cancer

    PubMed Central

    Ademuyiwa, Foluso O.; Ellis, Matthew J.; Ma, Cynthia X.

    2013-01-01

    Systemic treatment for triple negative breast cancer (TNBC: negative for the expression of estrogen receptor and progesterone receptor and HER2 amplification) has been limited to chemotherapy options. Neoadjuvant chemotherapy induces tumor shrinkage and improves the surgical outcomes of patients with locally advanced disease and also identifies those at high risk of disease relapse despite today's standard of care. By using pathologic complete response as a surrogate endpoint, novel treatment strategies can be efficiently assessed. Tissue analysis in the neoadjuvant setting is also an important research tool for the identification of chemotherapy resistance mechanisms and new therapeutic targets. In this paper, we review data on completed and ongoing neoadjuvant clinical trials in patients with TNBC and discuss treatment controversies that face clinicians and researchers when neoadjuvant chemotherapy is employed. PMID:23983689

  7. It Is Not Mandatory to Use Triple Rather Than Dual Anti-Platelet Therapy After a Percutaneous Coronary Intervention With a Second-Generation Drug-Eluting Stent

    PubMed Central

    Kim, Ju-Youn; Choi, Yun-Seok; Kwon, Ami; Chung, Woo-Baek; Park, Chul-Soo; Kim, Hee-Yeol; Chang, Kiyuk; Lee, Man-Young; Chung, Wook-Sung; Seung, Ki-Bae

    2015-01-01

    Abstract It has been shown that triple antiplatelet therapy with cilostazol results in better clinical outcomes than dual therapy in patients treated with a first-generation drug-eluting stent (DES); however, it is unclear whether triple antiplatelet therapy has a similar efficacy after the implantation of second-generation DES. In the COACT (Cath Olic medical center percutAneous Coronary in Tervention) registry, 1248 study subjects who underwent percutaneous coronary intervention with an everolimus- or zotarolimus-eluting stent (Endeavor, Xience V, or Promus) were analyzed. The patients were divided into 2 groups after propensity score matching (n = 724; M = 422 [58.3%]; mean age = 66.1 ± 11.0 years): Group 1: patients treated with dual antiplatelet drugs (aspirin and clopidogrel; n = 362; M = 213 [58.8%]; mean age = 65.6 ± 11.7 years); Group 2: patients treated with triple antiplatelet drugs (aspirin, clopidogrel, and cilostazol; n = 362; M = 209 [57.7%]; mean age = 65.6 ± 11.7 years). The mean follow-up duration was 13 ± 10 months, and the cumulative incidence of major cardiovascular events (MACE) was 6.3% in Group 1 and 7.7% in Group 2. There were no significant differences in MACE (death, nonfatal myocardial infarction, and stroke) between the 2 groups (OR, 1.210; 95% CI: 0.772–1.898; P = 0.406). Kaplan–Meier curves for MACE did not show any survival benefit for triple antiplatelet therapy, even in patients with acute coronary syndrome. In patients treated with a second-generation DES implantation, there is no added clinical benefit to using triple rather than dual antiplatelet therapy. PMID:26579817

  8. Triple versus dual antiplatelet therapy for coronary heart disease patients undergoing percutaneous coronary intervention: A meta-analysis.

    PubMed

    Zhou, Hong; Feng, Xiao-Ling; Zhang, Hong-Ying; Xu, Fei-Fei; Zhu, Jie

    2013-10-01

    Coronary heart disease (CHD) is the leading cause of mortality worldwide. Previous studies have suggested that cilostazol-based triple antiplatelet therapy (TAT) may be more effective than conventional dual antiplatelet therapy (DAT) at improving the clinical outcomes of patients with CHD undergoing percutaneous coronary intervention (PCI). However, individually published results are inconclusive. The present meta-analysis evaluated controlled clinical studies to compare the clinical outcomes between TAT and DAT in patients with CHD undergoing PCI. Ten controlled clinical studies were included, with a total of 7,670 patients with CHD undergoing PCI. The total number included 3,925 patients treated with DAT (aspirin and clopidogrel) and 3745 patients treated with TAT (addition of cilostazol to DAT). The crude odds ratio (OR) with a 95% confidence interval (CI) was calculated with either the fixed or random effects model. The meta-analysis results indicated that patients in the TAT group had a significantly lower rate of restenosis compared with that of the DAT group (OR=0.59, 95% CI: 0.45-0.77; P<0.001). The rate of major adverse cardiac events (MACE) and target lesion revascularization (TLR) in the TAT group were significantly lower compared with those in the DAT group (MACE: OR=0.69, 95% CI: 0.56-0.85, P<0.001; TLR: OR=0.61, 95% CI: 0.43-0.88, P=0.008). However, no significant differences between the TAT and DAT groups in terms of mortality rate, myocardial infarction, target vessel revascularization and stent thrombosis were observed. In conclusion, the results of the present meta-analysis indicated that the efficacy and safety of cilostazol-based TAT therapy is greater than that of conventional DAT therapy for patients with CHD undergoing PCI. PMID:24137311

  9. Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma.

    PubMed

    Tsimberidou, Apostolia M; McLaughlin, Peter; Younes, Anas; Rodriguez, Maria A; Hagemeister, Fredrick B; Sarris, Andreas; Romaguera, Jorge; Hess, Mark; Smith, Terry L; Yang, Ying; Ayala, Ana; Preti, Alejandro; Lee, Ming-Sheng; Cabanillas, Fernando

    2002-12-15

    Treatment for patients with stage IV indolent lymphoma ranges from watchful waiting to intensive chemotherapy and stem cell transplantation. In this trial we compared 2 induction regimens followed by 1 year of interferon maintenance therapy. Fludarabine, mitoxantrone (Novantrone), and dexamethasone (FND) were compared with an alternating triple therapy (ATT) regimen (CHOD-Bleo, ESHAP, and NOPP). Maintenance interferon/dexamethasone was given for 1 year in both treatment arms. Endpoints were comparisons of remission rates, survival, failure-free survival (FFS), molecular response rates, and toxicities. One hundred forty-two patients with previously untreated stage IV indolent lymphoma were evaluable (73 on FND; 69 on ATT). The overall response rates were 97% for FND and 97% for ATT (P =.9). The median follow-up is 5.9 years. The 5-year survival rates were 84% with FND and 82% with ATT (P =.9); the 5-year FFS rates were 41% with FND and 50% with ATT (P =.02). In a multivariate analysis, factors predicting for longer FFS were beta(2)-microglobulin less than 3 mg/L (P =.01) and ATT treatment (P =.03). ATT was associated with a substantially higher rate of grade 3-4 toxicities than FND. In conclusion, both regimens were associated with high rates of response and survival. ATT was associated with substantially longer FFS, but it was more toxic than FND. PMID:12393618

  10. Activatable albumin-photosensitizer nanoassemblies for triple-modal imaging and thermal-modulated photodynamic therapy of cancer.

    PubMed

    Hu, Dehong; Sheng, Zonghai; Gao, Guanhui; Siu, Fungming; Liu, Chengbo; Wan, Qian; Gong, Ping; Zheng, Hairong; Ma, Yifan; Cai, Lintao

    2016-07-01

    Photodynamic therapy (PDT) is a noninvasive and effective approach for cancer treatment. The main bottlenecks of clinical PDT are poor selectivity of photosensitizer and inadequate oxygen supply resulting in serious side effects and low therapeutic efficiency. Herein, a thermal-modulated reactive oxygen species (ROS) strategy using activatable human serum albumin-chlorin e6 nanoassemblies (HSA-Ce6 NAs) for promoting PDT against cancer is developed. Through intermolecular disulfide bond crosslinking and hydrophobic interaction, Ce6 photosensitizer is effectively loaded into the HSA NAs, and the obtained HSA-Ce6 NAs exhibit excellent reduction response, as well as enhanced tumor accumulation and retention. By the precision control of the overall body temperature instead of local tumor temperature increasing from 37 °C to 43 °C, the photosensitization reaction rate of HSA-Ce6 NAs increases 20%, and the oxygen saturation of tumor tissue raise 52%, significantly enhancing the generation of ROS for promoting PDT. Meanwhile, the intrinsic fluorescence and photoacoustic properties, and the chelating characteristic of porphyrin ring can endow the HSA-Ce6 NAs with fluorescence, photoacoustic and magnetic resonance triple-modal imaging functions. Upon irradiation of low-energy near-infrared laser, the tumors are completely suppressed without tumor recurrence and therapy-induced side effects. The robust thermal-modulated ROS strategy combined with albumin-based activatable nanophotosensitizer is highly potential for multi-modal imaging-guided PDT and clinical translation. PMID:27061266

  11. Nonbismuth concomitant quadruple therapy for Helicobacter pylori eradication in Chinese regions: A meta-analysis of randomized controlled trials

    PubMed Central

    Lin, Lien-Chieh; Hsu, Tzu-Herng; Huang, Kuang-Wei; Tam, Ka-Wai

    2016-01-01

    AIM: To evaluate the applicability of nonbismuth concomitant quadruple therapy for Helicobacter pylori (H. pylori) eradication in Chinese regions. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed to evaluate the efficacy of nonbismuth concomitant quadruple therapy between sequential therapy or triple therapy for H. pylori eradication in Chinese regions. The defined Chinese regions include China, Hong Kong, Taiwan, and Singapore. The primary outcome was the H. pylori eradication rate; the secondary outcome was the compliance with therapy. The PubMed, Embase, Scopus, and Cochrane databases were searched for studies published in the period up to March 2016 with no language restriction. RESULTS: We reviewed six randomized controlled trials and 1616 patients. In 3 trials comparing concomitant quadruple therapy with triple therapy, the H. pylori eradication rate was significantly higher for 7-d nonbismuth concomitant quadruple therapy than for 7-d triple therapy (91.2% vs 77.9%, risk ratio = 1.17, 95%CI: 1.09-1.25). In 3 trials comparing quadruple therapy with sequential therapy, the eradication rate was not significant between groups (86.9% vs 86.0%). However, higher compliance was achieved with concomitant therapy than with sequential therapy. CONCLUSION: The H. pylori eradication rate was higher for nonbismuth concomitant quadruple therapy than for triple therapy. Moreover, higher compliance was achieved with nonbismuth concomitant quadruple therapy than with sequential therapy. Thus, nonbismuth concomitant quadruple therapy should be the first-line treatment in Chinese regions. PMID:27340362

  12. A rational approach to single, dual and triple therapy in COPD.

    PubMed

    Calverley, Peter; Vlies, Ben

    2016-05-01

    The complexity of COPD treatment has increased over the last 5 years mainly because of the proliferation of drugs and delivery devices. In this paper, we will focus on currently available therapy used for maintaining patient well-being rather than acute relief of symptoms. We propose a series of principles for rational therapy, and following a review of how currently available treatments perform in isolation and when compared with each other, we suggest an approach to aid the rational selection of the most appropriate treatment based on current evidence. PMID:26611377

  13. Five-day bismuth-free triple therapy for the eradication of Helicobacter pylori and reduction of duodenal ulcer relapse

    SciTech Connect

    Coelho, L.G.; Passos, M.C.; Chausson, Y.; Castro L de, P. )

    1991-08-01

    Previous studies have demonstrated that the eradication of Helicobacter pylori (H. pylori) is associated with a significant reduction of the rate of duodenal ulcer (DU) relapse. The aim of this study was to assess the long-term effect of a bismuth-free triple therapy on the eradication of H. pylori and reduction of DU relapse. After informed consent, 61 patients with endoscopically proven DU and H. pylori infection detected on 14C-urea breath test (BT) were included in the study. All patients received a combination of furazolidone, amoxicillin, and metronidazole, three times a day, for 5 days, in addition to eventual classical antiulcer agents prescribed by their attending physicians. BT was repeated after an interval of at least 60 days to evaluate H. pylori eradication. Endoscopy and another BT were performed again at 6.5 months after therapy to detect possible recurrences. Forty-eight patients completed the trial: 26 (54%) patients were negative for H. pylori at 6.5 months after the end of treatment, and 22 (46%) persisted H. pylori positive. Ninety-two percent of the patients in whom the bacteria were eradicated showed endoscopically healed ulcers and were asymptomatic, and two that were symptomatic presented only occasional pain not requiring therapy. Among the 22 patients who persisted H. pylori positive, six (27%) showed endoscopically active ulcers (p = 0.012) and eight (36%) patients continued to be symptomatic (p less than 0.01), and were still using antiulcer drugs (p = 0.002) 6.5 months after treatment. It is concluded that combined treatment with furazolidone, amoxicillin, and metronidazole for 5 days represents a well-tolerated, inexpensive, and effective therapeutic regime for the eradication of H. pylori and abolition of DU relapse in more than 50% of the patients during a follow-up period of 6.5 months.

  14. Association of Triple Therapy with Improvement in Cholesterol Profiles over Two Year Follow-up in the TEAR Trial

    PubMed Central

    Charles-Schoeman, Christina; Wang, Xiaoyan; Lee, Yuen Yin; Shahbazian, Ani; Navarro-Millán, Iris; Yang, Shuo; Chen, Lang; Cofield, Stacey S; Moreland, Larry W; O’Dell, James; Bathon, Joan; Paulus, Harold; Bridges, S. Louis; Curtis, Jeffrey R

    2016-01-01

    Objective To evaluate long term changes in cholesterol levels in early rheumatoid arthritis (RA) patients randomized to initiate methotrexate (MTX) monotherapy, methotrexate + etanercept (MTX+ETA), or triple therapy (TT) [MTX + sulfasalazine (SSZ) + hydroxychloroquine (HCQ)] in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Methods Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed in 416 patients participating in the TEAR trial over 102 weeks of follow-up. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated measures analysis with mixed effect linear models to model the within-subject covariance over time. Results Mixed effect models controlling for traditional CV risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in DAS28, CRP, or ESR were associated with increases in HDL-C, LDL-C, and TC in all treatment groups (p values <0.001–0.035). TT was strongly associated with higher HDL-C and lower LDL-C and TC/HDL-C ratios (p values <0.001) compared to MTX monotherapy and MTX + ETA over two year follow-up. Conclusion Decreases in RA disease activity over long term follow-up was associated with increases in cholesterol in early RA patients treated with either biologic or non-biologic therapies. The use of TT over two year follow-up was associated with higher HDL-C and lower LDL-C and TC/HDL-C ratios compared to MTX monotherapy or MTX + ETA combination therapy. PMID:26606398

  15. Glucocorticoid receptor antagonism as a novel therapy for triple-negative breast cancer

    PubMed Central

    Skor, Maxwell N.; Wonder, Erin L.; Kocherginsky, Masha; Goyal, Anju; Hall, Ben A.; Cai, Yi; Conzen, Suzanne D.

    2013-01-01

    Purpose: Triple-negative breast cancer (TNBC) accounts for 10-20% of newly diagnosed invasive breast cancer. Finding effective targets for chemotherapy-resistant TNBC has proven difficult in part because of TNBC’s molecular heterogeneity. We have previously reported that, likely because of GR’s anti-apoptotic activity in ER-negative breast epithelial and cancer cells, high glucocorticoid receptor (GR) expression/activity in early-stage TNBC significantly correlates with chemotherapy-resistance and increased recurrence. We hypothesized that pre-treatment with mifepristone, a (GR)-antagonist, would potentiate the efficacy of chemotherapy in GR+ TNBC by inhibiting GR’s anti-apoptotic signaling pathways and increasing the cytotoxic efficiency of chemotherapy. Experimental Design: TNBC cell apoptosis was examined in the context of physiological glucocorticoid concentrations, chemotherapy, and/or pharmacologic concentrations of mifepristone. We used high-throughput live microscopy with continuous recording to measure apoptotic cells stained with a fluorescent dye, and Western analysis to detect caspase-3 and PARP cleavage. The effect of mifepristone on GR-mediated gene expression was also measured. TNBC xenograft studies were performed in female severe combined immunodeficient (SCID) mice and tumors were measured following treatment with vehicle, paclitaxel or mifepristone/paclitaxel. Results: We found that although mifepristone treatment alone had no significant effect on TNBC cell viability or clonogenicity in the absence of chemotherapy, the addition of mifepristone to dexamethasone/paclitaxel treatment significantly increased cytotoxicity and caspase-3/PARP cleavage. Mifepristone also antagonized GR-induced SGK1 and MKP1/DUSP1 gene expression, while significantly augmenting paclitaxel-induced GR+ MDA-MB-231 xenograft tumor shrinkage in vivo. Conclusions: These results suggest that mifepristone pre-treatment could be a useful strategy for increasing tumor cell

  16. Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial

    PubMed Central

    de Jong, P H; Hazes, J M; Han, H K; Huisman, M; van Zeben, D; van der Lubbe, P A; Gerards, A H; van Schaeybroeck, B; de Sonnaville, P B; van Krugten, M V; Luime, J J; Weel, A E

    2014-01-01

    Objectives To compare 1-year clinical efficacy of (1) initial triple disease-modifying antirheumatic drug therapy (iTDT) with initial methotrexate (MTX) monotherapy (iMM) and (2) different glucocorticoid (GC) bridging therapies: oral versus a single intramuscular injection in early rheumatoid arthritis. Methods In a single-blinded randomised clinical trial patients were randomised into three arms: (A) iTDT (methotrexate+sulfasalazine+hydroxychloroquine) with GCs intramuscularly; (B) iTDT with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. Primary outcomes were (1) area under the curve (AUC) of Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS) and (2) the proportion of patients with radiographic progression. Results 281 patients were randomly assigned to arms A (n=91), B (n=93) or C (n=97). The AUC DAS and HAQ were respectively −2.39 (95% CI −4.77 to −0.00) and −1.67 (95% CI −3.35 to 0.02) lower in patients receiving iTDT than in those receiving iMM. After 3 months, treatment failure occurred less often in the iTDT group, resulting in 40% fewer treatment intensifications. The difference in treatment intensifications between the arms required to maintain the predefined treatment goal remained over time. No differences were seen between the two GC bridging therapies. Respectively 21%, 24% and 23% of patients in arms A, B and C had radiographic progression after 1 year. Patients receiving iTDT had more adjustments of their medication owing to adverse events than those receiving iMM. Conclusions Treatment goals are attained more quickly and maintained with fewer treatment intensifications with iTDT than with iMM. However, no difference in radiographic progression is seen. Both GC bridging therapies are equally effective and, therefore, both can be used. Trial registration number ISRCTN26791028. PMID:24788619

  17. Down-regulating HIF-1α by lentivirus-mediated shRNA for therapy of triple negative breast cancer

    PubMed Central

    Li, Shuang; Wei, Qingzhu; Li, Qin; Zhang, Bin; Xiao, Qiang

    2015-01-01

    Hypoxia is associated with poor response to treatment in various cancers. Hypoxia inducible factor 1 (HIF-1) is a major transcription factor that mediates adaptation of cancer cells to a hypoxic environment and regulates many genes that are involved in key cellular functions, including cell immortalization, stem cell maintenance, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy. HIF-1α has been considered as an attractive therapeutic target for cancer treatment, but there is limited success in this research field. In the present study, we designed a recombinant lentivirus containing HIF-1α siRNA, developed stably transfected cell lines, and tested the anticancer effects of the siRNA on cancer cells in vitro and in vivo. Our results indicated that the stable downregulation of HIF-1α reversed chemoresistance, inhibited proliferation, migration and invasion of cancer cells, and slowed down the tumor growth in breast cancer xenograft models. In conclusion, the recombinant lentivirus containing HIF-1α siRNA provides a new avenue for developing novel therapy for triple negative breast cancer. PMID:25920936

  18. Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

    PubMed Central

    Silva, Fernando M; Eisig, Jaime N; Teixeira, Ana Cristina S; Barbuti, Ricardo C; Navarro-Rodriguez, Tomás; Mattar, Rejane

    2008-01-01

    Background The Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of Helicobacter pylori (H. pylori). This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of H. pylori eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole. Methods Sixty patients with peptic ulcer diagnosed by upper digestive endoscopy and H. pylori infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval. Results The eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high. Conclusion Despite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for H. pylori infection. PMID:18510773

  19. Down-regulating HIF-1α by lentivirus-mediated shRNA for therapy of triple negative breast cancer.

    PubMed

    Li, Shuang; Wei, Qingzhu; Li, Qin; Zhang, Bin; Xiao, Qiang

    2015-01-01

    Hypoxia is associated with poor response to treatment in various cancers. Hypoxia inducible factor 1 (HIF-1) is a major transcription factor that mediates adaptation of cancer cells to a hypoxic environment and regulates many genes that are involved in key cellular functions, including cell immortalization, stem cell maintenance, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy. HIF-1α has been considered as an attractive therapeutic target for cancer treatment, but there is limited success in this research field. In the present study, we designed a recombinant lentivirus containing HIF-1α siRNA, developed stably transfected cell lines, and tested the anticancer effects of the siRNA on cancer cells in vitro and in vivo. Our results indicated that the stable downregulation of HIF-1α reversed chemoresistance, inhibited proliferation, migration and invasion of cancer cells, and slowed down the tumor growth in breast cancer xenograft models. In conclusion, the recombinant lentivirus containing HIF-1α siRNA provides a new avenue for developing novel therapy for triple negative breast cancer. PMID:25920936

  20. Theranostic nanoparticles for enzyme-activatable fluorescence imaging and photodynamic/chemo dual therapy of triple-negative breast cancer

    PubMed Central

    Choi, Jaehee; Kim, Hyunjin

    2015-01-01

    Background Triple-negative breast cancer (TNBC) is a highly diverse group of cancers characterized by tumors that does not express estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2 (HER2) gene expression. TNBC is associated with poor prognosis due to high rate of recurrence and distance metastasis, lack of response to hormonal or HER2-targeted therapies, and partial response to chemotherapy. Hence, development of new therapeutic strategies to overcome such limitations is of great importance. Here we describe the application of photosensitizer-conjugated and camptothecin (CPT)-encapsulated hyaluronic acid (HA) nanoparticles as enzyme-activatable theranostic nanoparticles (EATNP) for near-infrared (NIR) fluorescence imaging and photodynamic/chemo dual therapy of TNBC. Methods For the preparation of EATNPs, chlorin e6 (Ce6), a second generation photosensitizer, was covalently conjugated to a monomethoxy poly(ethylene glycol)-grafted HA backbone. Ce6-conjugated HA (Ce6-HA) formed self-assembled nanoparticles (i.e., Ce6-HA NPs) in an aqueous solution. Subsequently, CPT, a topoisomerase 1 inhibitor with remarkable anticancer efficacy but with low water solubility, was encapsulated inside the hydrophobic core of Ce6-HA NPs thereby forming EATNPs. Results Fluorescence and singlet oxygen generation (SOG) of EATNPs are quenched in its native state. Treatment of EATNPs with hyaluronidase (HAdase) induces enzyme concentration-dependent activation of NIR fluorescence and SOG. Moreover, HAdase-mediated degradation of the nanoparticles also triggers the release of CPT from the EATNPs. In vitro confocal microscopy and cytotoxicity tests confirmed that EATNPs were efficiently introduced into MDA-MB-231 TNBC cell line, thereby inducing better cytotoxicity than that by free CPT. Additional light irradiation onto the EATNP-treated cells significantly increased therapeutic efficacy in TNBC, which indicates that EATNP plays an important role in

  1. The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients.

    PubMed

    Boursier, J; Ducancelle, A; Vergniol, J; Veillon, P; Moal, V; Dufour, C; Bronowicki, J-P; Larrey, D; Hézode, C; Zoulim, F; Fontaine, H; Canva, V; Poynard, T; Allam, S; De Lédinghen, V

    2015-12-01

    Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country. PMID:26216230

  2. Optimal antagonism of the Renin-Angiotensin-aldosterone system: do we need dual or triple therapy?

    PubMed

    Werner, Christian; Pöss, Janine; Böhm, Michael

    2010-07-01

    HeFT and CHARM-ADDED have shown that combined RAAS inhibition with an ACE inhibitor and ARB significantly reduced the morbidity endpoint in certain patient subgroups compared with standard therapy. However, in clinical practice, dual RAAS blockade is rarely employed, as seen, for instance, in the CORONA trial. The RALES and EPHESUS trials, investigating the effects of aldosterone blockade on cardiovascular outcomes in CHF patients, revealed that the addition of an aldosterone antagonist to standard heart failure therapy conferred powerful relative risk reductions for both morbidity and mortality. Future studies will elucidate whether this also holds true for patients who are asymptomatic or who have heart failure with preserved ejection fraction. In selected patients with renal disease, several studies have suggested that combined RAAS blockade brings about additional renoprotective antiproteinuric effects independent of blood pressure reduction, and large trials with robust endpoints are underway. In summary, combined therapy with several RAAS inhibitors is not recommended for all patients along the cardiorenovascular continuum. Patients with CHF with incomplete neuroendocrine blockade, as indicated, for example, by repetitive cardiac decompensation or refractory symptoms, might benefit from dual therapy as long as safety issues are well controlled. Finally, novel pharmacological agents such as the direct renin inhibitor aliskiren may provide additional therapeutic tools, but their role has yet to be established. PMID:20568830

  3. Human glioma cells transformed by IGF-I triple helix technology show immune and apoptotic characteristics determining cell selection for gene therapy of glioblastoma

    PubMed Central

    Ly, A; Duc, H T; Kalamarides, M; Trojan, L A; Pan, Y; Shevelev, A; François, J-C; Noël, T; Kane, A; Henin, D; Anthony, D D; Trojan, J

    2001-01-01

    Aims—Insulin-like growth factor type I (IGF-I) antisense cellular gene therapy of tumours is based on the following data: rat glioma or hepatoma cells transfected with the vector encoding IGF-I antisense cDNA lose their tumorigenicity and induce a tumour specific immune response involving CD8+ T cells. Recently, using the IGF-I triple helix approach in studies of tumorigenicity, major histocompatibility complex class I (MHC-I) antigens were demonstrated in rat glioma transfected cells. This study used comparative IGF-I antisense and triple helix technologies in human primary glioma cells to determine the triple helix strategy that would be most appropriate for the treatment of glioblastoma. Methods—The cells were transfected using the IGF-I triple helix expression vector, pMT-AG, derived from the pMT-EP vector. pMT-AG contains a cassette comprising a 23 bp DNA fragment transcribing a third RNA strand, which forms a triple helix structure within a target region of the human IGF-I gene. Using pMT-EP, vectors encoding MHC-I or B7 antisense cDNA were also constructed. Results—IGF-I triple helix transfected glioma cells are characterised by immune and apoptotic phenomena that appear to be related. The expression of MHC-I and B7 in transfected cells (analysed by flow cytometry) was accompanied by programmed cell death (detected by dUTP fluorescein terminal transferase labelling of nicked DNA and electron microscopic techniques). Cotransfection of these cells with MHC-I and B7 antisense vectors suppressed the expression of MHC-I and B7, and was associated with a pronounced decrease in apoptosis. Conclusion—When designing an IGF-I triple helix strategy for the treatment of human glioblastoma, the transfected tumour cells should have the following characteristics: the absence of IGF-I, thepresence of both MHC-I and B7 molecules, and signs of apoptosis. PMID:11477137

  4. Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study

    PubMed Central

    Chen, San-Chi; Chang, Peter Mu-Hsin

    2016-01-01

    Lessons Learned Cisplatin/tegafur/uracil/irinotecan triple combination therapy shows moderate response, especially in patients without previous chemoradiotherapy within the 6 months before this combination therapy. Toxicity is tolerable, and quality of life is improved in responders. Background. The prognosis is poor in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Triple combination therapy may increase tumor response. Methods. This phase I/II prospective trial first determined the dose-limiting toxicity and recommended dose of irinotecan with cisplatin and tegafur/uracil (UFUR) in phase I. Irinotecan was supplied at doses of 40, 50, 60, and 70 mg/m2 by using a standard 3+3 design. Doses of cisplatin and UFUR were held stable. In phase II, the recommended dose of irinotecan was administered intravenously (i.v.) over 90 min on day 1, with cisplatin 50 mg/m2 i.v. over 60 min also on day 1, and oral UFUR 200 mg twice a day for 5 days every 2 weeks a cycle. Results. In the phase I portion, 14 patients were enrolled, and the dose level of irinotecan at 60 mg/m2 was defined as the recommended dose for the phase II portion of the study. Among 43 patients enrolled in the phase II portion, complete response was seen in 2 patients (4.7%) and partial response in 10 patients (23.3%), and the disease control rate was 39.5%. In a subgroup analysis of patients whose prior chemoradiotherapy was more than 6 months earlier, a response rate of 40.7% and disease control rate of 59.3% were observed. Conclusion. Cisplatin/UFUR/irinotecan triple combination therapy is tolerated and effective for selected patients. Individualized choice of treatment will influence prognosis and quality of life in R/M HNSCC patients. PMID:27091418

  5. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia

    PubMed Central

    Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

    2015-01-01

    Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m2 in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3–4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). PMID:25749825

  6. Emergence of telaprevir-resistant variants detected by ultra-deep sequencing after triple therapy in patients infected with HCV genotype 1.

    PubMed

    Akuta, Norio; Suzuki, Fumitaka; Seko, Yuya; Kawamura, Yusuke; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Hara, Tasuku; Kobayashi, Mariko; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

    2013-06-01

    Using ultra-deep sequencing technology, the present was designed to investigate whether the emergence of telaprevir-resistant variants (amino acid substitutions of aa36, aa54, aa155, aa156, and aa170 positions in HCV NS3 region) after commencement of triple therapy of telaprevir/peginterferon (PEG-IFN)/ribavirin could be predicted at baseline in previous non-responders to dual therapy. Fourteen patients infected with HCV genotype 1 who did not respond to previous PEG-IFN/ribavirin, received a 24-week regimen of triple therapy, and were evaluated for appearance of telaprevir-resistant variants (amino acid substitutions of more than 0.2% among the total coverage) by ultra-deep sequencing. The sustained virological response rate was 28.6% (4 of 14 patients), which was significantly higher in patients with Arg70 (substitution at core aa70) and partial response (type of previous response to PEG-IFN/ribavirin) than in other patients. Telaprevir-resistant variants at baseline were detected in 7.1% (1 of 14 patients) by direct sequencing and in 21.4% (3 of 14 patients) by ultra-deep sequencing. The appearance of telaprevir-resistant variants was examined by ultra-deep sequencing in 10 who did not show sustained virological responders. De novo variants emerged at re-elevation of viral load, regardless of variant frequencies at baseline (one patient with very high frequency variants [T54S: 99.9%], two patients with very low frequency variants [V36A: 0.2%; and V170A: 0.4%], and seven patients of undetectable variants). It is concluded that it is difficult to predict at baseline the emergence of telaprevir-resistant variants after commencement of triple therapy in prior non-responders of HCV genotype 1, even with the use of ultra-deep sequencing. PMID:23588728

  7. Telaprevir- and Boceprevir-Based Triple Therapy for Hepatitis C in Liver Transplant Recipients with Advanced Recurrent Disease: A Multicenter Study

    PubMed Central

    Verna, Elizabeth C.; Saxena, Varun; Burton, James R.; O’Leary, Jacqueline G.; Dodge, Jennifer L.; Stravitz, Richard T.; Levitsky, Joshua; Trotter, James F.; Everson, Gregory T.; Brown, Robert S.; Terrault, Norah A.

    2016-01-01

    Background Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor (PI)-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis. Methods LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and safety. Results 45 patients with advanced fibrosis and 9 with cholestatic hepatitis (74% male, 57% with genotype 1a, and 63% prior non-responders) were included. SVR12 occurred in 51% of those with advanced fibrosis and 44% with cholestatic hepatitis, and eRVR was highly predictive of SVR12. Previous null/partial response (OR 0.09, p=0.003), low platelet count (OR 1.02, p=0.004), and steroid use (OR 0.16, p=0.03) were negatively associated with SVR12 in multivariable models. Six (11%) patients died during or after treatment, and hepatic decompensation during treatment occurred in 22% of patients with advanced fibrosis and 33% of patients with cholestatic hepatitis. Hispanic ethnicity (OR 9.37, p=0.03) and low albumin at treatment start (OR 0.01, p=0.001) were predictive of death or decompensation in multivariable models. Conclusions For LT recipients with recurrent advanced HCV and at highest need of effective treatment, PI-based triple therapy achieved sustained viral clearance in ~50% of patients. However, there is significant risk of serious adverse events including hepatic decompensation, arguing for earlier therapeutic intervention. The availability of antiviral drug combinations with higher efficacy and improved safety are of particular importance for post-transplant patients with advanced disease

  8. Adjunctive Triple Chronotherapy (Combined Total Sleep Deprivation, Sleep Phase Advance, and Bright Light Therapy) Rapidly Improves Mood and Suicidality in Suicidal Depressed Inpatients: An Open Label Pilot Study

    PubMed Central

    Sahlem, Gregory L.; Kalivas, Benjamin; Fox, James B.; Lamb, Kayla; Roper, Amanda; Williams, Emily N.; Williams, Nolan R.; Korte, Jeffrey E.; Zuschlag, Zachary D.; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S.; Uhde, Thomas W.; George, Mark S.; Short, E.Baron

    2014-01-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N=10, Mean age=44±16.4SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33–36 hours), followed by a three-night sleep phase advance along with four 30-minute sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7±4.2SD at baseline to a mean of 9.4±7.3SD on day five (p=.002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5±8.5SD at baseline to a mean of 7.2±5.5SD on day five (p=.01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed. PMID:25231629

  9. Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study.

    PubMed

    Sahlem, Gregory L; Kalivas, Benjamin; Fox, James B; Lamb, Kayla; Roper, Amanda; Williams, Emily N; Williams, Nolan R; Korte, Jeffrey E; Zuschlag, Zachary D; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S; Uhde, Thomas W; George, Mark S; Short, E Baron

    2014-12-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33-36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD on day five (p = .01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed. PMID:25231629

  10. Investigation of NS3 Protease Resistance-Associated Variants and Phenotypes for the Prediction of Treatment Response to HCV Triple Therapy

    PubMed Central

    Susser, Simone; Vermehren, Johannes; Peiffer, Kai-Henrik; Filmann, Natalie; Bon, Dimitra; Kuntzen, Thomas; Mauss, Stefan; Grammatikos, Georgios; Perner, Dany; Berkowski, Caterina; Herrmann, Eva; Zeuzem, Stefan; Bartenschlager, Ralf; Sarrazin, Christoph

    2016-01-01

    Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR. PMID:27281344

  11. Addition of clidinium-C to the 14-day proton-pump inhibitor-based triple therapy for Helicobacter pylori eradication

    PubMed Central

    Seyyedmajidi, Mohammadreza; Homapoor, Saba; Zanganeh, Elahe; Dadjou, Mohammad; Eskandari Nejad, Shahab; Tajik Galayeri, Mohammad Hadi; Vafaeimanesh, Jamshid

    2016-01-01

    Background: Triple therapy with a proton pump inhibitor and two antibiotics in Helicobacter pylori (HP) eradication is widely accepted, but this combination fails in a considerable number of cases. The aim of this study was to assess the effect of clidinium-C addition on HP eradication and to investigate the efficacy and safety of clidinium-C in prevention of drugs' side effects. Methods: A total of 200 histopathologically confirmed HP positive peptic ulcer enrolled in this study which were randomly assigned to two treatment groups: OAC (20 mg omeprazole bid, 1000 mg amoxicillin bid and 500 mg clarithromycin bid) and OAC + clidinium-C. The effect of treatment and adverse effects were compared 6 weeks after completion of treatment. A13C-urea breath test was performed to confirm HP eradication. Results: A total of 184 patients (90 in group A and 94 in group B) completed the treatment protocols. HP eradication was achieved in 71.1% in OAC versus 72.3% in OCA+clidinium-C, (P=0.73). The frequencies of abdominal pain and stool abnormality, among the side effects recorded during the therapy period, were significantly lower in group B (OCA+clidinium-C) (P=0.01 and P=0.001, respectively). Conclusion: Addition of clidinium-C to OCA triple therapy decreases abdominal pain and frequency of stool abnormalities without affecting HP eradication rate. Based on these findings addition of clidinium-C may increase patient's compliance. PMID:27386057

  12. A Randomised Trial of empiric 14-day Triple, five-day Concomitant, and ten-day Sequential Therapies for Helicobacter pylori in Seven Latin American Sites

    PubMed Central

    Greenberg, E. Robert; Anderson, Garnet L.; Morgan, Douglas R.; Torres, Javier; Chey, William D.; Bravo, Luis Eduardo; Dominguez, Ricardo L.; Ferreccio, Catterina; Herrero, Rolando; Lazcano-Ponce, Eduardo C.; Meza-Montenegro, Mercedes María; Peña, Rodolfo; Peña, Edgar M.; Salazar-Martínez, Eduardo; Correa, Pelayo; Martínez, María Elena; Valdivieso, Manuel; Goodman, Gary E.; Crowley, John J.; Baker, Laurence H.

    2011-01-01

    Summary Background Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradicating Helicobacter pylori (H. pylori) infection than five-day concomitant and ten-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses and thus may be suitable for eradication programs in low-resource settings. Studies are limited from Latin America, however, where the burden of H. pylori-associated diseases is high. Methods We randomised 1463 men and women ages 21–65 selected from general populations in Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites) who tested positive for H. pylori by a urea breath test (UBT) to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); five days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or five days of lansoprazole and amoxicillin followed by five of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by UBT six–eight weeks after randomisation. Findings In intention-to-treat analyses, the probability of eradication with standard therapy was 82·2%, which was 8·6% higher (95% adjusted CI: 2·6%, 14·5%) than with concomitant therapy (73·6%) and 5·6% higher (95% adjusted CI: −0·04%, 11·6%) than with sequential therapy (76·5%). In analyses limited to the 1314 participants who adhered to their assigned therapy, the probabilities of eradication were 87·1%, 78·7%, and 81·1% with standard, concomitant, and sequential therapies, respectively. Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. Interpretation Standard 14-day triple-drug therapy is preferable to five-day concomitant or ten-day sequential four-drug regimens as empiric therapy for H. pylori

  13. Integration of photothermal therapy and synergistic chemotherapy by a porphyrin self-assembled micelle confers chemosensitivity in triple-negative breast cancer.

    PubMed

    Su, Shishuai; Ding, Yanping; Li, Yiye; Wu, Yan; Nie, Guangjun

    2016-02-01

    Triple-negative breast cancer is a malignant cancer type with a high risk of early recurrence and distant metastasis. Unlike other breast cancers, triple-negative breast cancer is lack of targetable receptors and, therefore, patients largely receive systemic chemotherapy. However, inevitable adverse effects and acquired drug resistance severely constrain the therapeutic outcome. Here we tailor-designed a porphyrin-based micelle that was self-assembled from a hybrid amphiphilic polymer comprising polyethylene glycol, poly (d, l-lactide-co-glycolide) and porphyrin. The bilayer micelles can be simultaneously loaded with two chemotherapeutic drugs with synergistic cytotoxicity and distinct physiochemical properties, forming a uniform and spherical nanostructure. The drug-loaded micelles showed a tendency to accumulate in the tumor and can be internalized by tumor cells for drug release in acidic organelles. Under near-infrared laser irradiation, high density of self-quenched porphyrins in the hydrophobic layer absorbed light efficiently and converted into an excited state, leading to the release of sufficient heat for photothermal therapy. The integration of localized photothermal effect and synergistic chemotherapy conferred great chemosensitivity to cancer cells and achieved tumor regression using about 1/10 of traditional drug dosage. As a result, chemotherapy-associated adverse effects were successfully avoided. Our present study established a novel porphyrin-based nanoplatform with photothermal activity and expanded drug loading capacity, providing new opportunities for challenging conventional chemotherapy and fighting against stubborn triple-negative breast cancer. PMID:26708642

  14. HCV triple therapy in co-infection HIV/HCV is not associated with a different risk of developing major depressive disorder

    PubMed Central

    Fialho, Renata; Keller, Majella; File, Alex; Woods, Catherine; Pereira, Marco; Yousseff, Elaney; Tibble, Jeremy; Harrison, Neil; Fisher, Martin; Rusted, Jennifer; Whale, Richard

    2014-01-01

    Introduction Hepatitis C (HCV) treatment options have changed with the development of direct activity antivirals (DAAs) and the availability of triple therapies have improved HCV cure rates. A common neuropsychiatric side effect of pegylated-interferon and ribavirin treatment is major depressive disorder (MDD), however little is known about such adverse events with protease inhibitor-based triple therapy. The aim of this study was to assess the rate of MDD in co-infected HIV HCV patients undergoing different HCV treatments. Methods All participants were co-infected HIV HCV attending the Royal Sussex County Hospital Brighton hepatology outpatient clinic between 2010 and 2014. Participants were assessed for DSM-IV MDD and depression severity (using the Hamilton depression scale (HAMD)) at baseline and monthly after treatment initiation. HIV and HCV stages, genotype, reinfection and standard demographic variables were recorded. Influence of HCV stage (acute vs. chronic) and type of treatment (classic vs triple), emergence of MDD and clearance outcomes were analyzed using repeated measures and logistic regression models. Results Fifty participants with a mean age of 42.65 years (SD=10.32) were included; most were male (98%). The majority had contracted HCV genotype 1 (64%) or 4 (26%). The HCV stage and treatment groups were matched for age and depression at baseline. No significant differences were found on virological outcomes considering HCV stage and treatment. From baseline to SVR, there was a significant increase in HAMD scores, F(4,36)=10.09, p<.001; this was not significantly influenced by HCV stage, F(4,35)=0.54, p=.708 or HCV treatment group, F(4,35)=0.60, p=.664. Those with chronic HCV were more likely to transition to MDD than acute infection (OR 7.77, 95% CI 2.04–29.54, p=.003). No differences were found for depression emergence by HCV treatment group (OR 0.83, 95% CI 0.22–3.13, p=.787). Conclusions HCV triple therapy was not associated with a different

  15. Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study

    PubMed Central

    Mori, Hideki; Matsuzaki, Juntaro; Tsugawa, Hitoshi; Fukuhara, Seiichiro; Miyoshi, Sawako; Hirata, Kenro; Seino, Takashi; Matsushita, Misako; Nishizawa, Toshihiro; Masaoka, Tatsuhiro; Kanai, Takanori

    2015-01-01

    Background and aim This prospective randomized study was designed to assess the efficacy of 10-day and 14-day rifabutin-based triple therapy as a third- or fourth-line rescue therapy. Methods Patients who failed first- and second-line eradication therapy were enrolled. H. pylori was isolated from gastric biopsy specimens and the rpoB mutation status, a factor of resistance to rifamycins, and minimum inhibitory concentrations (MICs) of rifabutin and amoxicillin were determined. Enrolled patients were randomly assigned to receive 10-day or 14-day eradication therapy with esomeprazole (20 mg, 4 times a day (q.i.d.)), amoxicillin (500 mg, q.i.d.), and rifabutin (300 mg, once a day (q.d.s.)). Poor compliance was defined as intake of <80% of study drugs. Successful H. pylori eradication was confirmed using a [13C] urea breath test or a stool antigen test, 12 weeks after the end of therapy. Results Twelve patients were assigned to the 10-day group, and 17, to the 14-day group. Intention-to-treat and per-protocol analyses of eradication rates were 83.3% and 81.8% for the 10-day group and 94.1% and 91.7% for the 14-day group, respectively. All patients with rpoB mutation-positive strains (n = 3) showed successful eradication, irrespective of the regimen received. Therapy was stopped due to adverse events in 8.3% and 29.3% of patients in the 10-day and 14-day groups, respectively. Conclusion Both the 10-day and 14-day therapies were effective as rescue regimens. In particular, the 14-day therapy resulted in successful eradication in over 90% of patients, but the 10-day treatment may be enough to obtain a successful eradication rate, considering the tolerability of therapy. PMID:27403304

  16. Amoxicillin plus omeprazole versus triple therapy for eradication of Helicobacter pylori in duodenal ulcer disease: a prospective, randomized, and controlled study.

    PubMed Central

    Labenz, J; Gyenes, E; Rühl, G H; Börsch, G

    1993-01-01

    Treatment with amoxicillin and omeprazole resulted in encouraging Helicobacter pylori eradication rates in pilot studies that included medium term follow up. These results were evaluated in a prospective, randomised and controlled study. Forty patients with active duodenal ulcer disease and H pylori colonisation of the gastric mucosa were randomly assigned to receive either omeprazole (20 mg twice daily) and amoxicillin suspension (500 mg four times daily) for two weeks (group I) or bismuth subsalicylate (600 mg three times daily), metronidazole (400 mg three times daily), tetracycline (500 mg three times daily), and ranitidine (300 mg in the evening) for two weeks (group II). Study medication was followed in both groups by a four week treatment course with 300 mg ranitidine up to the final examination. One patient from each group was lost to follow up. H pylori was eradicated in 78.9% of group I and 84.2% of group II (p = 1.00). All ulcers in patients on omeprazole plus amoxicillin healed but in the triple treatment group four patients had residual peptic lesions after six weeks (ulcer healing rate: 78.9%, p = 0.11). Complete pain relief occurred after a median duration of 1 day in group I and of 6 days in group II (p = 0.03). There were no major complications in either group but minor side effects were more frequently recorded in patients on triple therapy (63.2% v 15.8%, p < 0.01). In conclusion, two weeks of treatment with omeprazole plus amoxicillin is as good as triple therapy plus ranitidine in eradicating H pylori but seems better with regard to safety, pain relief, and ulcer healing. Thus, amoxicillin plus omeprazole should be recommended as the treatment of choice in eradicating H pylori in patients with duodenal ulcer disease. PMID:8406147

  17. Relationship between the early boceprevir-S isomer plasma concentrations and the onset of breakthrough during HCV genotype 1 triple therapy.

    PubMed

    Boglione, L; De Nicolò, A; Cardellino, C S; Ruggiero, T; Ghisetti, V; Cariti, G; Di Perri, G; D'Avolio, A

    2015-02-01

    In a prospective cohort of 18 patients treated with boceprevir, we examined the role of boceprevir plasma concentration at the onset of breakthrough during the treatment. Nine patients experienced breakthrough during therapy. The resistance patterns were as follows: S122S/R, I132V, T54A/I132V, V156S/I170A, V36M/T54S/R155K, V36M/R155K and T54/R155K. Boceprevir-S isomer (SCH 534128) median concentration in patients with breakthrough was 48.3 ng/mL (interquartile range 43-58 ng/mL); in others, it was significantly (p 0.019) higher: 151 ng/mL. Low boceprevir plasma concentration can lead to virologic resistance; therapeutic drug monitoring should be used to prevent the onset of viral breakthrough during triple-regimen therapy with boceprevir. PMID:25658567

  18. A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient

    PubMed Central

    Ali, Siraj M.; Watson, Jessica; Wang, Kai; Chung, Jon H.; McMahon, Caitlin; Ross, Jeffrey S.; Dicke, Karel A.

    2016-01-01

    After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients. PMID:27293397

  19. A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient.

    PubMed

    Ali, Siraj M; Watson, Jessica; Wang, Kai; Chung, Jon H; McMahon, Caitlin; Ross, Jeffrey S; Dicke, Karel A

    2016-01-01

    After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients. PMID:27293397

  20. Triple antithrombotic therapy in patients with atrial fibrillation undergoing coronary artery stenting: hovering among bleeding risk, thromboembolic events, and stent thrombosis

    PubMed Central

    2012-01-01

    Dual antiplatelet treatment with aspirin and clopidogrel is the antithrombotic treatment recommended after an acute coronary syndrome and/or coronary artery stenting. The evidence for optimal antiplatelet therapy for patients, in whom long-term treatment oral anticoagulation is mandatory, is however scarce. To evaluate the safety and efficacy of the various antithrombotic strategies adopted in this population, we reviewed the available evidence on the management of patients receiving oral anticoagulation, such as a vitamin-k-antagonists, referred for coronary artery stenting. Atrial fibrillation is the most frequent indication for oral anticoagulation. The need of starting antiplatelet therapy in this clinical scenario raises concerns about the combination to choose: triple therapy with warfarin, aspirin, and a thienopyridine being the most frequent and advised. The safety of this regimen appeared suboptimal because of an increased risk in hemorrhagic complications. On the other hand, the combination of oral anticoagulation and an antiplatelet agent is suboptimal in preventing thromboembolic events and stent thrombosis; dual antiplatelet therapy may be considered only when a high hemorrhagic risk and low thromboembolic risk are perceived. Indeed, the need for prolonged multiple-drug antithrombotic therapy increases the bleeding risks when drug eluting stents are used. Since current evidence derives mainly from small, single-center and retrospective studies, large-scale prospective multicenter studies are urgently needed. PMID:23075316

  1. Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic

    PubMed Central

    Volpe, Massimo; Tocci, Giuliano

    2012-01-01

    Hypertension is a growing global health problem, and is predicted to affect 1.56 billion people by 2025. Treatment remains suboptimal, with control of blood pressure achieved in only 20%–35% of patients, and the majority requiring two or more antihypertensive drugs to achieve recommended blood pressure goals. To improve blood pressure control, the European hypertension guidelines recommend that angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) are combined with calcium channel blockers (CCBs) and/or thiazide diuretics. The rationale for this strategy is based, in part, on their different effects on the renin-angiotensin system, which improves antihypertensive efficacy. Data from a large number of trials support the efficacy of ACEIs or ARBs in combination with CCBs and/or hydrochlorothiazide (HCTZ). Combining two different classes of antihypertensive drugs has an additive effect on lowering of blood pressure, and does not increase adverse events, with the ARBs showing a tolerability advantage over the ACEIs. Among the different ARBs, olmesartan medoxomil is available as a dual fixed-dose combination with either amlodipine or HCTZ, and the increased blood pressure-lowering efficacy of these two combinations is proven. Triple therapy is required in 15%–20% of treated uncontrolled hypertensive patients, with a renin-angiotensin system blocker, CCB, and thiazide diuretic considered to be a rational combination according to the European guidelines. Olmesartan, amlodipine, and HCTZ are available as a triple fixed-dose combination, and significant blood pressure reductions have been observed with this regimen compared with the possible dual combinations. The availability of these fixed-dose combinations should lead to improvement in blood pressure control and aid compliance with long-term therapy, optimizing the management of this chronic condition. PMID:22745561

  2. ITPA and SLC29A1 Genotyping for the Prediction of Ribavirin Dose Reduction in Anti-HCV Triple Therapy with Protease Inhibitors.

    PubMed

    Lombardi, Andrea; Landonio, Simona; Magni, Carlo; Cheli, Stefania; Mazzali, Cristina; Mondelli, Mario U; Rizzardini, Giuliano; Clementi, Emilio; Falvella, Felicia Stefania

    2015-01-01

    Chronic hepatitis C is one of the most important causes of liver disease, leading to cirrhosis, hepatic decompensation and hepatocellular carcinoma. Recently some important advances in therapy have been achieved with the introduction of first wave, first generation direct acting antiviral agents (DAAs) such as boceprevir (BOC), in combination with pegylated interferon (Peg-IFN) and ribavirin (RBV). The superior rate of sustained virological response with this treatment is accompanied by an elevated frequency of anaemia. Several studies have evidenced the importance of single nucleotide polymorphisms (SNPs) in inosine triphosphatase (ITPA) and solute carrier family 29, member 1 (SLC29A1) genes in the development of this adverse event. Here, we investigated haemoglobin levels and the best-known functional SNPs in ITPA and SLC29A1 genes in 22 patients treated with triple therapy with BOC/Peg-IFN/RBV. The identification of ITPA protective and SLC29A1 risk genotypes still appears to be a current methodology in RBV dosing during hepatitis C virus therapy with DAAs. PMID:26279293

  3. Efficacy of Low-Level Laser Therapy in Relieving Nipple Pain in Breastfeeding Women: A Triple-Blind, Randomized, Controlled Trial.

    PubMed

    Coca, Kelly Pereira; Marcacine, Karla Oliveira; Gamba, Mônica Antar; Corrêa, Luciana; Aranha, Ana Cecília Corrêa; Abrão, Ana Cristina Freitas de Vilhena

    2016-08-01

    Pain accruing from nipple lesions caused by inadequate latching by the baby is a common complaint among breastfeeding women and an important obstacle to successful breastfeeding. Nipple pain occurs during the first days after delivery and is considered one of the main causes for early weaning. To investigate the efficacy of low-level laser therapy as a treatment for nipple pain due to breastfeeding. A triple-blind, randomized, clinical study. A university-affiliated hospital in São Paulo, Brazil. Fifty-nine women with nipple lesions at the time of their admission. Thirty women (intervention group) received three sessions of laser therapy (InGaAIP laser, 660 nanometer, 40 milliwatts of power, 5 Joules per square centimeter of energy density for 5 seconds each, total energy = 0.6 Joules) in the region of the nipples at three different points in time (0 hour, 24 hours, and 48 hours after diagnosis of nipple lesion). Twenty-nine women with similar clinical conditions were randomly assigned to the control group. Self-reported pain was recorded before and after laser therapy using a visual analogue scale. The intervention group experienced a decrease of 2.0 centimeters in intensity of pain (p = .016) 24 hours after the first intervention and also presented lower levels of pain compared with the control group. Low-level laser therapy was considered effective for treating nipple lesions in breastfeeding women with pain, providing relief and prolonging exclusive breastfeeding. More clinical trials with different laser dosimetry and parameters are necessary to optimize laser therapy protocols for breastfeeding women. PMID:27363734

  4. Helicobacter pylori eradication: Sequential therapy and Lactobacillus reuteri supplementation

    PubMed Central

    Efrati, Cesare; Nicolini, Giorgia; Cannaviello, Claudio; O’Sed, Nicole Piazza; Valabrega, Stefano

    2012-01-01

    AIM: To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori). METHODS: H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies: (1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation during antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS: Ninety adult dyspeptic patients were enrolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment: 11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen: 32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in eradication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after

  5. Novel cell-penetrating peptide-loaded nanobubbles synergized with ultrasound irradiation enhance EGFR siRNA delivery for triple negative Breast cancer therapy.

    PubMed

    Jing, Hui; Cheng, Wen; Li, Shouqiang; Wu, Bolin; Leng, Xiaoping; Xu, Shouping; Tian, Jiawei

    2016-10-01

    The lack of safe and effective gene delivery strategies remains a bottleneck for cancer gene therapy. Here, we describe the synthesis, characterization, and application of cell-penetrating peptide (CPP)-loaded nanobubbles (NBs), which are characterized by their safety, strong penetrating power and high gene loading capability for gene delivery. An epidermal growth factor receptor (EGFR)-targeted small interfering RNA (siEGFR) was transfected into triple negative breast cancer (TNBC) cells via prepared CPP-NBs synergized with ultrasound-targeted microbubble destruction (UTMD) technology. Fluorescence microscopy showed that siEGFR and CPP were loaded on the shells of the NBs. The transfection efficiency and cell proliferation levels were evaluated by FACS and MTT assays, respectively. In addition, in vivo experiments showed that the expression of EGFR mRNA and protein could be efficiently downregulated and that the growth of a xenograft tumor derived from TNBC cells could be inhibited. Our results indicate that CPP-NBs carrying siEGFR could potentially be used as a promising non-viral gene vector that can be synergized with UTMD technology for efficient TNBC therapy. PMID:27388967

  6. Highly porous PEGylated Bi2S3 nano-urchins as a versatile platform for in vivo triple-modal imaging, photothermal therapy and drug delivery.

    PubMed

    Li, Zhenglin; Hu, Ying; Chang, Manli; Howard, Kenneth A; Fan, Xuelei; Sun, Ye; Besenbacher, Flemming; Yu, Miao

    2016-09-21

    Biocompatible single-component nanoplatforms simultaneously integrating multiple therapeutic functions with multiple imaging modes are desirable for anticancer treatments. Herein, elaborately-designed highly porous PEGylated bismuth sulfide nano-urchins (Bi2S3-PEG NUs) have been successfully synthesized by using Bi2O3 nanospheres as the sacrificial template via the hydrothermal process. It is demonstrated that the Bi2S3-PEG NUs possess high compatibility, stability, X-ray attenuation ability, near-infrared (NIR) absorbance and photothermal conversion capability, without noticeable toxicity. Based on both in vitro and in vivo results, the product shows excellent performance in highly effective photothermal therapy (PTT) guided by triple-modal imaging, including X-ray computed tomography (CT), and photoacoustic (PA) and infrared thermal (IRT) imaging, without noticeable toxicity in vivo. Importantly, the NUs are highly porous with a high specific surface area and copious mesopores, providing high loading capacity to accommodate drugs (or guest biomolecules) for further applications in chemotherapy and other additional functions. Doxorubicin is loaded as an example, showing a rather high loading capacity (∼37.9%) together with a bimodal on-demand pH/photothermal-sensitive drug release property. Such fascinating multifunctional nanoagents may have considerable applications in antitumor diagnosis and therapy in the clinic. PMID:27545304

  7. Inhibition of fibrosis and inflammation by triple therapy with pirfenidone, edaravone and erythropoietin in rabbits with drug-induced lung injury: comparison of CT imaging and pathological findings.

    PubMed

    Watanabe, Shobu; Nitta, Norihisa; Sonoda, Akinaga; Nitta-Seko, Ayumi; Ohta, Shinichi; Tsuchiya, Keiko; Otani, Hideji; Tomozawa, Yuki; Nagatani, Yukihiro; Mukaisho, Kenichi; Takahashi, Masashi; Murata, Kiyoshi

    2013-11-01

    In a rabbit model of bleomycin-induced lung injury, computed tomography (CT) and pathological studies were conducted to investigate whether the progression of this injury is inhibited by pirfenidone and by triple therapy with pirfenidone, edaravone and erythropoietin. We divided nine rabbits with bleomycin-induced lung injury into three equally sized groups. Group 1 served as the control, group 2 received pirfenidone alone and group 3 was treated with pirfenidone, edaravone and erythropoietin. Multidetector CT (MDCT) scans were acquired immediately after the administration of bleomycin, and further scans were performed on days 14 and 28. The area of abnormal opacity was calculated. The rabbit lungs were removed and the size of abnormal areas in macroscopic specimens was calculated and the degree of fibrosis and inflammation in microscopic specimens was scored. In order, the average size of the area of abnormal opacity on CT scans was largest in group 1, followed by groups 2 and 3. On day 28, the area of opacity was significantly smaller in group 3 than in group 1 (P=0.071). The average size of the area of abnormal opacity on macroscopic findings was largest in group 1, followed in order by groups 2 and 3; the difference between group 1 and 3 was significant (P<0.05). The average fibrosis score was highest in group 3 followed by groups 2 and 1. By contrast, the average inflammation score was highest in group 2 followed by groups 1 and 3. Although the administration of pirfenidone alone slowed the progression of bleomycin-induced lung injury, the triple-drug combination was more effective. PMID:24223628

  8. Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer.

    PubMed

    Camarda, Roman; Zhou, Alicia Y; Kohnz, Rebecca A; Balakrishnan, Sanjeev; Mahieu, Celine; Anderton, Brittany; Eyob, Henok; Kajimura, Shingo; Tward, Aaron; Krings, Gregor; Nomura, Daniel K; Goga, Andrei

    2016-04-01

    Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor-, progesterone receptor- or human epidermal growth factor 2 receptor-positive (RP) breast cancer. We and others have shown that MYC alters metabolism during tumorigenesis. However, the role of MYC in TNBC metabolism remains mostly unexplored. We hypothesized that MYC-dependent metabolic dysregulation is essential for the growth of MYC-overexpressing TNBC cells and may identify new therapeutic targets for this clinically challenging subset of breast cancer. Using a targeted metabolomics approach, we identified fatty acid oxidation (FAO) intermediates as being dramatically upregulated in a MYC-driven model of TNBC. We also identified a lipid metabolism gene signature in patients with TNBC that were identified from The Cancer Genome Atlas database and from multiple other clinical data sets, implicating FAO as a dysregulated pathway that is critical for TNBC cell metabolism. We found that pharmacologic inhibition of FAO catastrophically decreased energy metabolism in MYC-overexpressing TNBC cells and blocked tumor growth in a MYC-driven transgenic TNBC model and in a MYC-overexpressing TNBC patient-derived xenograft. These findings demonstrate that MYC-overexpressing TNBC shows an increased bioenergetic reliance on FAO and identify the inhibition of FAO as a potential therapeutic strategy for this subset of breast cancer. PMID:26950360

  9. A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4)

    PubMed Central

    Choi, Philip Young-Ill; Roncolato, Fernando; Badoux, Xavier; Ramanathan, Sundra; Ho, Shir-Jing

    2015-01-01

    Promising reports of combination immunosuppression with high-dose dexamethasone and rituximab for the treatment of primary immune thrombocytopenia (ITP) have recently emerged. They suggest a potential to further optimize the efficacy of therapy. We investigate the use of a novel combination of conventional therapies in ITP given over 4 weeks. From 2011 to 2014, 20 patients were prospectively enrolled onto a single-arm phase 2b study to describe the safety, efficacy, and tolerability of oral dexamethasone 40 mg for days 1 to 4, oral cyclosporine 2.5 to 3 mg/kg daily for day 1 to 28, and intravenous low-dose rituximab 100 mg for days 7, 14, 21, and 28. There were no therapy-related serious adverse side effects, 6-month response rate was 60%, and treatment was well tolerated. Responders enjoyed relapse-free survivals of 92% and 76%, respectively, at 12 and 24 months. This study highlights the possibility of achieving an enduring remission from 4 weeks of therapy. This study is registered at www.anzctr.org.au (#ANZCTRN12611000015943). PMID:25972158

  10. Improved Helicobacter pylori Eradication Rate of Tailored Triple Therapy by Adding Lactobacillus delbrueckii and Streptococcus thermophilus in Northeast Region of Thailand: A Prospective Randomized Controlled Clinical Trial

    PubMed Central

    Tongtawee, Taweesak; Dechsukhum, Chavaboon; Leeanansaksiri, Wilairat; Kaewpitoon, Soraya; Kaewpitoon, Natthawut; Loyd, Ryan A.; Matrakool, Likit; Panpimanmas, Sukij

    2015-01-01

    Background and Aim. To evaluate the effect of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus to Helicobacter pylori eradication in different periods of therapeutic protocol. Methods. Infected patients were randomized to one-week tailored triple therapy (esomeprazole 20 mg bid, clarithromycin 500 mg bid/metronidazole 400 mg tid if clarithromycin resistant, and amoxicillin 1000 mg bid) with placebo (group 1, n=100); one week of pretreatment with probiotics (group 2, n=100); and one week of pretreatment with probiotic followed by one week of the same probiotics after treatment (group 3, n=100). Result. PP analysis involved 292 patients, 98 in group 1, 97 in group 2, and 97 in group 3. Successful eradication was observed in 229 patients; by PP analysis, the eradication rates were significantly higher (P<0.01, 95% CI; 0.71–0.97) in group 2 and group 3 than group 1. ITT analysis eradication rates were significantly higher in group 2 and group 3 than group 1 (P<0.01 95% CI; 0.72–0.87), and there is no significant difference between the three groups (P=0.32) in terms of adverse events. Conclusion. Adding probiotics before or before and after tailored treatment can improve Helicobacter pylori eradication rates. This trial is registered with Thai Clinical Trials Registry number: TCTR20141209001. PMID:26167176

  11. Controlled-release triple anti-inflammatory therapy based on novel gastroretentive sponges: characterization and magnetic resonance imaging in healthy volunteers.

    PubMed

    Tadros, Mina Ibrahim; Fahmy, Rania Hassan

    2014-09-10

    The current work aimed to develop novel composite sponges of chitosan (CH)-chondroitin sulfate (CS) as a low-density gastroretentive delivery system for lornoxicam (LOR). This triple anti-inflammatory therapy-loaded matrices are expected to expand and float upon contact with gastric fluids for prolonged times. CH and CS solutions (3%, w/w) were prepared, mixed in different ratios, lyophilized, coated with magnesium stearate and compressed. The CH:CS interpolymer complex (IPC) was evaluated via FT-IR, DSC, and XRD. The compressed-sponges were evaluated for appearance, structure, porosity, pore diameter, density, wetting-time, floating characteristics, adhesion-retention, and LOR-release. The gastroretentivity of the best achieved magnetite-loaded sponges was monitored in healthy volunteers via MRI. The interaction between CH (protonated amino groups) and CS (anionic carboxylate/sulfate groups) proved IPC formation. DSC and XRD studies confirmed loss of LOR crystallinity. The sponges possessed interconnecting porous-network structures. The porosity, mean pore diameter, and bulk density of CH:CS (10:3) IPC sponges were 11.779%, 25.4 nm, and 0.670 g/mL, respectively. They showed complete wetting within seconds, gradual size-expansion within minutes and prolonged adhesion for hours. Controlled LOR-release profiles were tailored over 12h to satisfy individual patient needs. Monitoring of sponges via MRI proved their gastroretentivity for at least 5h. PMID:24928130

  12. [Prolonged remission achieved by using bevacizumab plus paclitaxel therapy combined with sequential radiotherapy for a rapidly growing chest wall recurrence of triple negative breast cancer - a case report].

    PubMed

    Kawashima, Masahiro; Fujii, Kazuhiro; Kiso, Marina; Takeyama, Osamu; Kan, Shugen; Tanaka, Mitsuru

    2015-01-01

    A 73-year-old woman, who was diagnosed with right triple negative breast cancer (cT1cN1M0, stage I ) and underwent right modified radical mastectomy with axillary lymph node dissection, showed recurrent disease in the right parasternal lymph node 4 years after the operation. Computed tomography (CT) revealed rapid growth of the tumor along with pain, accompanied by the destruction of the sternal bone. Five cycles of bevacizumab plus paclitaxel (BEV+wPTX) treatment (10 mg/kg of bevacizumab on days 1 and 15 plus 90 mg/m² of paclitaxel on days 1, 8, and 15 every 4 weeks)achieved remarkable tumor regression. Parasternal irradiation (30 Gy/15 Fr) followed by oral capecitabine treatment (600 mg b. i. d; 3 week administration followed by a week of rest) as maintenance therapy showed complete tumor regression and helped to achieve good quality of life (QOL) without any unfavorable symptoms at the 2-year follow-up, although the estimated progression free survival of this treatment is about 6 months. As BEV+wPTX had a high response rate for recurrent breast cancer, its combination with sequential radiotherapy could provide a favorable local control rate and good QOL for patients with rapidly growing, solitary, recurrent breast cancers. PMID:25596684

  13. The efficacy and safety of adding the probiotic Saccharomyces boulardiito standard triple therapy for eradication of H.pylori: a randomized controlled trial

    PubMed Central

    Ghobakhlou, Mehdi; Rajabalinia, Hassan; Ataei, Elnaz; Jahani Sherafat, Somayeh; Moghimi-Dehkordi, Bijan; Bahreiny, Rasoul

    2013-01-01

    Aim Evaluating the efficacy and safety of adding the probiotic Saccharomyces boulardiito standard triple therapy for eradication of Helicobacter pylori. Background Several probiotics such as Saccharomyces boulardii have been investigated for their clinical efficacy. This probiotic, inhibit H. pylori urease by lowering the gastric pH, adhesion of H. pylori to gastric epithelial cells, stabilize the gastric barrier function and reduce the side effects of antibiotics. Patients and methods In this randomized controlled trial we evaluated 160 adult patients with biopsy confirmed H. Pylori infection referred to gastroenterology ward of Taleghani hospital. The patients were randomized into two treatment regimens: patients in group A (n = 80) were given amoxicillin (1000 mg, b.i.d), clarithromycin (500 mg, b.i.d), omeprazole (20 mg, b.i.d) and probiotic of saccaromyces boularidi (Yomogi) (250 mg, b.i.d) for 14 days, moreover patients in group B (n = 80) were given amoxicillin (1000 mg, b.i.d), clarithromycin (500 mg b.i.d) and omeprazole (20 mg,b.i.d) for 14 days. Results 160 patients (66 male 41.25%, 94female 58.75%) with the mean age of 47.1±11.4 years were evaluated. The success rate for H. pylori eradication in group A was higher 75(87.5%) than group B 65 (81.2%), but the difference between two groups was not significant (p = 0.350). Moreover, in case group side effects as nausea, diarrhea, abdominal discomfort and bloating were significantly lower than control group in first and second weeks. Conclusion This study showed that saccaromyces boularidi decreased the adverse effects associated with H.pylori therapy but did not significantly decrease the eradication rate of H.pylori. PMID:24834296

  14. Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs.

    PubMed

    Arain, A; Bourgeois, S; de Galocsy, C; Henrion, J; Deltenre, P; d'Heygere, F; George, C; Bastens, B; Van Overbeke, L; Verrando, R; Bruckers, L; Mathei, C; Buntinx, F; Van Vlierberghe, H; Francque, S; Laleman, W; Moreno, C; Janssens, F; Nevens, F; Robaeys, G

    2016-01-01

    No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow-up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non-PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non-PWID); with a non-inferiority test with -5% margin there is a difference of -1% (95% CI [-15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies. PMID:26121975

  15. Influence of Genes Suppressing Interferon Effects in Peripheral Blood Mononuclear Cells during Triple Antiviral Therapy for Chronic Hepatitis C

    PubMed Central

    Iijima, Sayuki; Matsuura, Kentaro; Watanabe, Tsunamasa; Onomoto, Koji; Fujita, Takashi; Ito, Kyoko; Iio, Etsuko; Miyaki, Tomokatsu; Fujiwara, Kei; Shinkai, Noboru; Kusakabe, Atsunori; Endo, Mio; Nojiri, Shunsuke; Joh, Takashi; Tanaka, Yasuhito

    2015-01-01

    The levels of expression of interferon-stimulated genes (ISGs) in liver are associated with response to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV). However, associations between the responses of ISGs to IFN-based therapy and treatment efficacy or interleukin-28B (IL28B) genotype have not yet been determined. Therefore, we investigated the early responses of ISGs and interferon-lambdas (IFN-λs) in peripheral blood mononuclear cells (PBMCs) during PEG-IFN/RBV plus NS3/4 protease inhibitor (PI) therapy. We prospectively enrolled 50 chronic hepatitis C patients with HCV genotype 1, and collected PBMCs at baseline, 8 and 24 h after the initial administration of PEG-IFN/RBV/PI. Levels of mRNAs for selected ISGs and IFN-λs were evaluated by real-time PCR. All 31 patients with a favorable IL28B genotype and 13 of 19 with an unfavorable genotype achieved sustained virological responses (SVR). Levels of mRNA for A20, SOCS1, and SOCS3, known to suppress antiviral activity by interfering with the IFN signaling pathway, as well as IRF1 were significantly higher at 8 h in patients with an unfavorable IL28B genotype than in those with a favorable one (P = 0.007, 0.026, 0.0004, 0.0006, respectively), especially in the non-SVR group. Particularly, the fold-change of IRF1 at 8 h relative to baseline was significantly higher in non-SVR than in SVR cases with an unfavorable IL28B genotype (P = 0.035). In conclusion, levels of several mRNAs of genes suppressing antiviral activity in PBMCs during PEG-IFN/RBV/PI differed according to IL28B genotypes, paralleling treatment efficacy. PMID:25706116

  16. Replacement of clarithromycin with azithromycin in triple therapy regimens for the eradication of helicobacter pylori: A randomized clinical trial

    PubMed Central

    Khoshnood, A; Hakimi, P; Salman-Roghani, H; Reza Mirjalili, M

    2014-01-01

    Abstract Background: Eradication of helicobacter pylori is important for treatment of GU but an ideal regimen is not available. HP is resistant to metronidazole and clarithromycin. Clarithromycin is expensive and is not available in under developing countries. This study aimed to compare two regimens containing clarithromycin or azithromycin. Methods: Totally, seventy-eight patients with GU (confirmed with endoscopy) and infection of HP (Confirmed by Rapid Urease Test (RUT)) were allocated to one of the groups of study (35 participants in each group). Two weeks regimen of Clarithromycin (2×500 mg) + Amoxicillin (2×1 gr) + omeprazole (2×20 mg) was administered for group A of patients while group B got a 10 days regimen of Azithromycin (1×250 mg) + 14 days Amoxicillin (2×1 gr) + omeprazole (2×20 mg). At the end of the treatment course, the patients were evaluated according to the side effects of the drugs. In addition, two months after the end of therapy, patients underwent endoscopy and biopsy to evaluate HP eradication. Results: After two weeks, the side effects of the drug were: Nausea 8 patients in group A and 7 patients in group B, Diarrhea 2 patients in group A, 3 patients in group B and vomiting 2 patients in group A, 3 patients in group B. There were no serious side effects in any group. Eradication rate in group A was 82.9% (based on per protocol analysis (PPA)) and 84.6 % (intention to treat (ITT)). In group B, eradication rate was 77.1 % (PPA) and 79.5 % (ITT) (P=0.55). Conclusion: Based on our study results, azithromycin can be used in HP eradication regimen because of its similar efficacy to clarithromycin but also have lower cost, side effects and resistance. PMID:25408735

  17. A phase III randomised controlled trial of single-dose triple therapy in COPD: the IMPACT protocol.

    PubMed

    Pascoe, Steven J; Lipson, David A; Locantore, Nicholas; Barnacle, Helen; Brealey, Noushin; Mohindra, Rajat; Dransfield, Mark T; Pavord, Ian; Barnes, Neil

    2016-08-01

    Patients with symptomatic advanced chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations are particularly at risk of poor outcomes and present a significant burden on healthcare systems. The relative merits of treating with different inhaled combination therapies e.g. inhaled corticosteroids (ICS)/long-acting β2-agonist (LABA), LABA/long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, in this patient group are poorly understood, as is reflected in current guidelines. The InforMing the PAthway of COPD Treatment (IMPACT) study will evaluate the efficacy and safety of fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI over a 52-week treatment period. The study has been designed with a focus on understanding the comparative merits of each treatment modality in different phenotypes/endotypes.This is a phase III, randomised, double-blind, three-arm, parallel-group, global multicentre study comparing the rate of moderate and severe exacerbations between FF/UMEC/VI and FF/VI or UMEC/VI over a 52-week treatment period. The study aims to recruit 10 000 patients from approximately 1070 centres. Eligible patients are aged ≥40 years, with symptomatic advanced COPD (Global initiative for chronic Obstructive Lung Disease (GOLD) group D) and an exacerbation in the previous 12 months.The first patients were recruited to the IMPACT study (ClinicalTrials.gov: NCT02164513) in June 2014 and the anticipated completion date is July 2017. PMID:27418551

  18. Triple gastric peptic ulcer perforation.

    PubMed

    Radojkovic, Milan; Mihajlovic, Suncica; Stojanovic, Miroslav; Stanojevic, Goran; Damnjanovic, Zoran

    2016-03-01

    Patients with advanced or metastatic cancer have compromised nutritional, metabolic, and immune conditions. Nevertheless, little is known about gastroduodenal perforation in cancer patients. Described in the present report is the case of a 41-year old woman with stage IV recurrent laryngeal cancer, who used homeopathic anticancer therapy and who had triple peptic ulcer perforation (PUP) that required surgical repair. Triple gastric PUP is a rare complication. Self-administration of homeopathic anticancer medication should be strongly discouraged when evidence-based data regarding efficacy and toxicity is lacking. PMID:27193988

  19. The risk of bleeding of triple therapy with vitamin K-antagonists, aspirin and clopidogrel after coronary stent implantation: Facts and questions

    PubMed Central

    Rubboli, Andrea

    2011-01-01

    Background Triple therapy (TT) with vitamin K-antagonists (VKA), aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation (PCI-S) in patients with an indication for oral anticoagulation. TT is associated with an increased risk of bleeding, but available evidence is flawed by important limitations, including the limited size and the retrospective design of most of the studies, as well as the rare reporting of the incidence of in-hospital bleeding and the treatment which was actually ongoing at the time of bleeding. Since the perceived high bleeding risk of TT may deny patients effective strategies, the determination of the true safety profile of TT is of paramount importance. Methods All the 27 published studies where the incidence of bleeding at various time points during follow-up has been reported separately for patients on TT were reviewed, and the weakness of the data was analyzed. Results The absolute incidence of major bleeding upon discharge at in-hospital, ≤ 1 month, 6 months, 12 months and ≥ 12 months was: 3.3% ± 1.9%, 5.1% ± 6.7%, 8.0% ± 5.2%, 9.0% ± 8.0, and 6.2% ± 7.8%, respectively, and not substantially different from that observed in previous studies with prolonged dual antiplatelet treatment with aspirin and clopidogrel. Conclusions While waiting for the ongoing, large-scale, registries and clinical trials to clarify the few facts and to answer the many questions regarding the risk of bleeding of TT, this treatment should not be denied to patients with an indication for VKA undergoing PCI-S provided that the proper measures and cautions are implemented. PMID:22783307

  20. Aprepitant versus ondansetron in preoperative triple-therapy treatment of nausea and vomiting in neurosurgery patients: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background The incidence of postoperative nausea and vomiting (PONV) is 50% to 80% after neurosurgery. The common prophylactic treatment for postoperative nausea and vomiting is a triple therapy of droperidol, promethazine and dexamethasone. Newer, more effectives methods of prophylaxis are being investigated. We designed this prospective, double-blind, single-center study to compare the efficacy of ondansetron, a neurokinin-1 antagonist, and aprepitant, as a substitute for droperidol, in the prophylactic treatment of postoperative nausea and vomiting after neurosurgery. Methods After obtaining institutional review board approval; 176 patients, 18 to 85 years of age with American Society of Anesthesiologists (ASA) classifications I to III, who did not receive antiemetics 24 h before surgery and were expected to undergo general anesthesia for neurosurgery lasting longer than 2 h were included in this study. After meeting the inclusion and exclusion criteria and providing written informed consent, patients were randomly assigned in a 1:1 ratio to one of two treatment groups: aprepitant or ondansetron. The objective of this study was to conduct a randomized, double-blind, double-dummy, parallel-group and single-center trial to compare and evaluate the efficacies of aprepitant versus ondansetron. Patients received oral aprepitant 40 mg OR oral dummy pill within 2 h prior to induction. At induction, a combination of intravenous dexamethasone 10 mg, promethazine 25 mg, and ondansetron 4 mg OR dummy injection was administered. Therefore, all patients received one dummy treatment and three active PONV prophylactic medications: dexamethasone 10 mg, promethazine 25 mg, and either aprepitant 40 mg OR ondansetron 4 mg infusion. The primary outcome measures were the episodes and severity of nausea and vomiting; administration of rescue antiemetic; and opioid consumption for 120 h postoperatively. Standard safety assessments included adverse event

  1. Targeted Cancer Therapy: Correlative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity (Adv. Healthcare Mater. 11/2016).

    PubMed

    Othman, Basmah A; Greenwood, Christina; Abuelela, Ayman F; Bharath, Anil A; Chen, Shu; Theodorou, Ioannis; Douglas, Trevor; Uchida, Maskai; Ryan, Mary; Merzaban, Jasmeen S; Porter, Alexandra E

    2016-06-01

    On page 1310 J. S. Merzaban, A. E. Porter, and co-workers present fluorescently labeled RGD-targeted ZnO nanoparticles (NPs; green) for the targeted delivery of cytotoxic ZnO to integrin αvβ3 receptors expressed on triple negative breast cancer cells. Correlative light-electron microscopy shows that NPs dissolve into ionic Zn(2+) (blue) upon uptake and cause apoptosis (red) with intra-tumor heterogeneity, thereby providing a possible strategy for targeted breast cancer therapy. Cover design by Ivan Gromicho. PMID:27275627

  2. Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study

    PubMed Central

    About, Frédégonde; Oudot-Mellakh, Tiphaine; Niay, Jonathan; Rabiéga, Pascaline; Pedergnana, Vincent; Duffy, Darragh; Sultanik, Philippe; Cagnot, Carole; Carrat, Fabrice; Marcellin, Patrick; Zoulim, Fabien; Larrey, Dominique; Hézode, Christophe; Fontaine, Hélène; Bronowicki, Jean-Pierre; Pol, Stanislas; Albert, Matthew L.; Theodorou, Ioannis

    2015-01-01

    Background Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1. Patients and Methods A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model. Results None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50–3.70], P = 2x10-4). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82–8.92], P = 8x10-4). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10-5). Conclusion Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy. PMID:26670100

  3. Potent efficacy of metronomic topotecan and pazopanib combination therapy in preclinical models of primary or late stage metastatic triple-negative breast cancer

    PubMed Central

    Man, Shan; Bocci, Guido; Kerbel, Robert S.

    2015-01-01

    Metronomic chemotherapy has shown promising activity in numerous preclinical studies and also some phase II clinical studies involving various tumor types, and is currently undergoing phase III trial evaluation. Triple-negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and very poor prognosis following progression after standard chemotherapeutic regimens. Herein, we evaluated the potential therapeutic impact and molecular mechanisms of topotecan administered in a continuous low-dose metronomic (LDM) manner, alone or in concurrent combination with pazopanib, an antiangiogenic tyrosine kinase inhibitor (TKI), in a triple-negative, primary and metastatic breast cancer orthotopic model; potential molecular mechanisms of efficacy were also studied, especially the impact of hypoxic conditions. The combination of metronomic topotecan and pazopanib significantly enhanced antitumor activity compared to monotherapy with either drug and prolonged survival, even in the advanced metastatic survival setting, with a marked decrease in tumor vascularity, proliferative index, and the induction of apoptosis. Significant changes in tumor angiogenesis, cancer cell proliferation, apoptosis, HIF1α levels, HIF-1 target genes and ABCG2 were found both in vitro and in tumor tissue. Notably, the pazopanib and metronomic topotecan combination treatment inhibited expression of HIF1α and ABCG2 genes in cells grown under hypoxic conditions, and this was associated with an increased intracellular concentration of the active form of topotecan. Our results suggest a potential novel therapeutic option for the treatment of metastatic triple-negative breast cancer patients. PMID:26623560

  4. The Na+ /H+ exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells

    PubMed Central

    Amith, Schammim Ray; Wilkinson, Jodi Marie; Baksh, Shairaz; Fliegel, Larry

    2015-01-01

    Dysregulation of Na+ /H+ exchanger isoform one (NHE1) activity is a hallmark of cells undergoing tumorigenesis and metastasis, the leading cause of patient mortality. The acidic tumor microenvironment is thought to facilitate the development of resistance to chemotherapy drugs and to promote extracellular matrix remodeling leading to metastasis. Here, we investigated NHE1 as a co-adjuvant target in paclitaxel chemotherapy of metastatic breast cancer. We generated a stable NHE1-knockout of the highly invasive, triple-negative, MDA-MB-231 breast cancer cells. The NHE1-knockout cells proliferated comparably to parental cells, but had markedly lower rates of migration and invasion in vitro. In vivo xenograft tumor growth in athymic nude mice was also dramatically decreased compared to parental MDA-MB-231 cells. Loss of NHE1 expression also increased the susceptibility of knockout cells to paclitaxel-mediated cell death. NHE1 inhibition, in combination with paclitaxel, resulted in a dramatic decrease in viability, and migratory and invasive potential of triple-negative breast cancer cells, but not in hormone receptor-positive, luminal MCF7 cells. Our data suggest that NHE1 is critical in triple-negative breast cancer metastasis, and its chemical inhibition boosts the efficacy of paclitaxel in vitro, highlighting NHE1 as a novel, potential co-adjuvant target in breast cancer chemotherapy. PMID:25514463

  5. Potent efficacy of metronomic topotecan and pazopanib combination therapy in preclinical models of primary or late stage metastatic triple-negative breast cancer.

    PubMed

    Di Desidero, Teresa; Xu, Ping; Man, Shan; Bocci, Guido; Kerbel, Robert S

    2015-12-15

    Metronomic chemotherapy has shown promising activity in numerous preclinical studies and also some phase II clinical studies involving various tumor types, and is currently undergoing phase III trial evaluation. Triple-negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and very poor prognosis following progression after standard chemotherapeutic regimens. Herein, we evaluated the potential therapeutic impact and molecular mechanisms of topotecan administered in a continuous low-dose metronomic (LDM) manner, alone or in concurrent combination with pazopanib, an antiangiogenic tyrosine kinase inhibitor (TKI), in a triple-negative, primary and metastatic breast cancer orthotopic model; potential molecular mechanisms of efficacy were also studied, especially the impact of hypoxic conditions. The combination of metronomic topotecan and pazopanib significantly enhanced antitumor activity compared to monotherapy with either drug and prolonged survival, even in the advanced metastatic survival setting, with a marked decrease in tumor vascularity, proliferative index, and the induction of apoptosis. Significant changes in tumor angiogenesis, cancer cell proliferation, apoptosis, HIF1α levels, HIF-1 target genes and ABCG2 were found both in vitro and in tumor tissue. Notably, the pazopanib and metronomic topotecan combination treatment inhibited expression of HIF1α and ABCG2 genes in cells grown under hypoxic conditions, and this was associated with an increased intracellular concentration of the active form of topotecan. Our results suggest a potential novel therapeutic option for the treatment of metastatic triple-negative breast cancer patients. PMID:26623560

  6. Triple therapy with salmeterol/fluticasone propionate 50/250 plus tiotropium bromide improve lung function versus individual treatments in moderate-to-severe Japanese COPD patients: a randomized controlled trial – Evaluation of Airway sGaw after treatment with tripLE

    PubMed Central

    Saito, Takefumi; Takeda, Akinori; Hashimoto, Katsuji; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Hagan, Gerald W

    2015-01-01

    Purpose Triple therapy using salmeterol/fluticasone propionate (FP) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease (COPD), but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients. The effects of of salmeterol/fluticasone propionate 50/250 μg (SFC250) twice daily plus tiotropium 18 μg (TIO) once daily and individual treatments on lung function were compared. Patients and methods Fifty three Japanese COPD patients participated in this randomized, double-blind, double-dummy, Williams square design crossover study. Lung function was assessed by plethysmography and spirometry. Results The primary endpoint of postdose specific airway conductance area under the curve (AUC0–4h) on day 28 was significantly higher following SFC250 + TIO (0.854) compared with TIO (0.737, 15.8%) and SFC250 (0.663, 28.8%) alone. SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO (0.161 L, P<0.001) and SFC250 (0.103 L, P=0.008). SFC250 + TIO significantly improved residual volume compared with TIO (P<0.001) and SFC250 (P=0.003) on day 28. Nonsignificant improvements were seen in trough inspiratory capacity, total lung capacity, and thoracic gas volume. There was no mean change seen in rescue medication. Conclusion Triple therapy using SFC250 + TIO was well tolerated and gave a greater improvement in bronchodilation compared with TIO and SFC250 alone in Japanese patients with COPD. There was improvement in few symptoms, but no mean change was seen in patient-reported outcomes measured by rescue medication use. PMID:26604737

  7. A comparative study of broccoli sprouts powder and standard triple therapy on cardiovascular risk factors following H.pylori eradication: a randomized clinical trial in patients with type 2 diabetes

    PubMed Central

    2014-01-01

    Background In this clinical trial we compared the effects of broccoli sprouts powder, as an alternative and complementary treatment, to those of standard triple therapy, as a common medical treatment, on cardiovascular risk factors following the H.pylori eradication in patients with type 2 diabetes. Methods Eighty-six type 2 diabetic patients with positive H.pylori stool antigen test (HpSAg) were randomized to receive one of the three following regimens: STT) Standard triple therapy (omeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, twice a day for 14 days), BSP) 6 g/d broccoli sprouts powder for 28 days, and combination of these as STT + BSP. After 4 weeks of treatment, H.pylori eradication rates were assessed by HpSAg. Anthropometric measures, blood pressure, serum lipids and lipoproteins as well as serum high sensitive- C reactive protein were also assessed at baseline and at the second examination. Results Seventy-seven participants completed the study [STT (n = 28), BSP (n = 25), STT + BSP (n = 24)]. The H.pylori eradication rates were 89.3%, 56.0% and 91.7% in STT, BSP and STT + BSP groups, respectively. After the treatment, both systolic and diastolic blood pressure significantly decreased in STT + BSP group (P < 0.05). Serum triglycerides and TG/HDL-C ratio increased in STT patients group (<0.05). Serum hs-CRP levels significantly decreased in the patients who were treated with BSP per se (3.0 ± 2.5 at baseline vs. 2.3 ± 2.1 after the treatment, P < 0.05). Conclusion Compared to standard triple therapy, BSP regimen in addition to considerable effects on H.pylori eradication had also favorable properties on cardiovascular risk factors following the H.pylori eradication. PMID:24940565

  8. Taking Triple Aim at the Triple Aim.

    PubMed

    Bryan, Stirling; Donaldson, Cam

    2016-01-01

    Since its introduction to the USA, the Triple Aim is now being adopted in the healthcare systems of other advanced economies. Verma and Bhatia (2016) (V&B) argue that provincial governments in Canada now need to step up to the plate and lead on the implementation of a Triple Aim reform program here. Their proposals are wide ranging and ambitious, looking for governments to act as the "integrators" within the healthcare system, and lead the reforms. Our view is that, as a vision and set of goals for the healthcare system, the Triple Aim is all well and good, but as a pathway for system reform, as articulated by V&B, it misses the mark in at least three important respects. First, the emphasis on improvement driven by performance measurement and pay-for-performance is troubling and flies in the face of emerging evidence. Second, we know that scarcity can be recognized and managed, even in politically complex systems, and so we urge the Triple Aim proponents to embrace more fully notions of resource stewardship. Third, if we want to take seriously "population health" goals, we need to think very differently and consider broader health determinants; Triple Aim innovation targeted at healthcare systems will not deliver the goals. PMID:27009583

  9. Counting Primitive Pythagorean Triples

    ERIC Educational Resources Information Center

    Ayoub, Ayoub B.

    2005-01-01

    A triple (x,y,z) of natural numbers is called a Primitive Pythagorean Triple (PPT) if it satisfies two conditions: (1) x[squared] + y[squared] = z[squared]; and (2) x, y, and z have no common factor other than one. All the PPT's are given by the parametric equations: (1) x = m[squared] - n[squared]; (2) y = 2mn; and (3) z = m[squared] +…

  10. Optical frequency tripling with improved suppression and sideband selection.

    PubMed

    Thakur, Manoj P; Medeiros, Maria C R; Laurêncio, Paula; Mitchell, John E

    2011-12-12

    A novel optical dispersion tolerant millimetre-wave radio-over-fibre system using optical frequency tripling technique with enhanced and selectable sideband suppression is demonstrated. The implementation utilises cascaded optical modulators to achieve either an optical single sideband (OSSB) or double sideband-suppressed carrier (DSB-SC) signal with high sideband suppression. Our analysis and simulation results indicate that the achievable suppression ratio of this configuration is only limited by other system factors such as optical noise and drifting of the operational conditions. The OSSB transmission system performance is assessed experimentally by the transport of 4 WiMax channels modulating a 10 GHz optical upconverted RF carrier as well as for optical frequency doubling and tripling. The 10 GHz and tripled carrier at 30 GHz are dispersion tolerant resulting both in an average relative constellation error (RCE) of -28.7 dB after 40 km of fibre. PMID:22274056

  11. The effects of symbiotic therapy on anthropometric measures, body composition and blood pressure in patient with metabolic syndrome: a triple blind RCT

    PubMed Central

    Rabiei, Samira; Shakerhosseini, Rahebeh; Saadat, Navid

    2015-01-01

    Background: Increase in prevalence of obesity and type 2 diabetes which are of the main risk factors of metabolic syndrome, is not only the result of changes in genetic, diet or physical activity, but also an imbalance of micro flora may play an important role. Therefore, alteration of micro flora using pre/probiotic is considered as a new strategy for treatment of metabolic disorders. Methods: The current study is a triple blind randomized controlled trial. 46 patients from both sexes, who fulfilled inclusion criteria, randomly categorized into intervention or placebo group. The intervention and placebo groups consumed 2 probiotic capsules or 2 placebo capsules during 3 months, respectively. Both groups received a weight loss diet, according to their adjusted ideal body weight. Anthropometric, body composition, blood pressure and nutritional measurements were done in the beginning, at 6th week, and at the end of the study. T-test and paired-t test were used for statistical analysis. Results: 40 patients completed the study. BMI, WC, HC, fat mass, lean mass and blood pressure were reduced in all participants (p< 0.05). Systolic blood pressure in symbiotic group was less than placebo group, significantly (p< 0.05). The trend of weight loss in symbiotic group continued at least for 12 weeks while it was stopped at week 6 in placebo group. Conclusion: Symbiotic supplement with the weight loss diet had synergistic effects on improvement in systolic blood pressure and anthropometric measurements. Based on our findings, symbiotic can postpone plateau phase of weight loss and it may prevent resistance to further weight loss. PMID:26478871

  12. Triple Point Topological Metals

    NASA Astrophysics Data System (ADS)

    Zhu, Ziming; Winkler, Georg W.; Wu, QuanSheng; Li, Ju; Soluyanov, Alexey A.

    2016-07-01

    Topologically protected fermionic quasiparticles appear in metals, where band degeneracies occur at the Fermi level, dictated by the band structure topology. While in some metals these quasiparticles are direct analogues of elementary fermionic particles of the relativistic quantum field theory, other metals can have symmetries that give rise to quasiparticles, fundamentally different from those known in high-energy physics. Here, we report on a new type of topological quasiparticles—triple point fermions—realized in metals with symmorphic crystal structure, which host crossings of three bands in the vicinity of the Fermi level protected by point group symmetries. We find two topologically different types of triple point fermions, both distinct from any other topological quasiparticles reported to date. We provide examples of existing materials that host triple point fermions of both types and discuss a variety of physical phenomena associated with these quasiparticles, such as the occurrence of topological surface Fermi arcs, transport anomalies, and topological Lifshitz transitions.

  13. Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients

    PubMed Central

    Marcellin, Patrick; Lapalus, Martine; Khelifa-Mouri, Feryel; Boyer, Nathalie; Zoulim, Fabien; Serfaty, Lawrence; Bronowicki, Jean-Pierre; Martinot-Peignoux, Michelle; Lada, Olivier; Asselah, Tarik; Dorival, Céline; Hézode, Christophe; Carrat, Fabrice; Nicot, Florence; Peytavin, Gilles; Mentré, France; Guedj, Jeremie

    2014-01-01

    Triple therapy combining a protease inhibitor (PI) (telaprevir or boceprevir), pegylated interferon (PEG-IFN), and ribavirin (RBV) has dramatically increased the chance of eradicating hepatitis C virus (HCV). However, the efficacy of this treatment remains suboptimal in cirrhotic treatment-experienced patients. Here, we aimed to better understand the origin of this impaired response by estimating the antiviral effectiveness of each drug. Fifteen HCV genotype 1-infected patients with compensated cirrhosis, who were nonresponders to prior PEG-IFN/RBV therapy, were enrolled in a nonrandomized study. HCV RNA and concentrations of PIs, PEG-IFN, and RBV were frequently assessed in the first 12 weeks of treatment and were analyzed using a pharmacokinetic/viral kinetic model. The two PIs achieved similar levels of molar concentrations (P = 0.5), but there was a significant difference in the 50% effective concentrations (EC50) (P = 0.008), leading to greater effectiveness for telaprevir than for boceprevir in blocking viral production (99.8% versus 99.0%, respectively, P = 0.002). In all patients, the antiviral effectiveness of PEG-IFN was modest (43.4%), and there was no significant contribution of RBV exposure to the total antiviral effectiveness. The second phase of viral decline, which is attributed to the loss rate of infected cells, was slow (0.19 day−1) and was higher in patients who subsequently eradicated HCV (P = 0.03). The two PIs achieved high levels of antiviral effectiveness. However, the suboptimal antiviral effectiveness of PEG-IFN/RBV and the low loss of infected cells suggest that a longer treatment duration might be needed in cirrhotic treatment-experienced patients and that a future IFN-free regimen may be particularly beneficial in these patients. PMID:24982076

  14. Outpatient triple chronotherapy for bipolar depression: case report.

    PubMed

    Gottlieb, John F; Terman, Michael

    2012-09-01

    There is an urgent need for rapid, effective, and safe treatments for bipolar depression. Triple chronotherapy is a combination of sleep deprivation, sleep phase advance, and bright light therapy that has been shown to induce accelerated and sustained remissions in bipolar depression. This case report describes the first outpatient program designed to administer triple chronotherapy and reviews the organizational and clinical requirements for providing such care. PMID:22995965

  15. Pythagorean Triples from Harmonic Sequences.

    ERIC Educational Resources Information Center

    DiDomenico, Angelo S.; Tanner, Randy J.

    2001-01-01

    Shows how all primitive Pythagorean triples can be generated from harmonic sequences. Use inductive and deductive reasoning to explore how Pythagorean triples are connected with another area of mathematics. (KHR)

  16. Overcoming Triple Segregation

    ERIC Educational Resources Information Center

    Gandara, Patricia

    2010-01-01

    Latinos are, after whites, the most segregated student group in the United States, and their segregation is closely tied to poor academic outcomes. Latinos experience a triple segregation: by race/ethnicity, poverty, and language. Racial segregation perpetuates negative stereotypes, reduces the likelihood of a strong teaching staff, and is often…

  17. Nearly Isosceles Pythagorean Triples.

    ERIC Educational Resources Information Center

    Ryden, Robert

    1983-01-01

    The nature of an investigation into numbers termed Nearly Isosceles Pythagorean Triples (NIPTs) is detailed. The exploration, even though it is stated to have no practical value, is defended as helping pupils see the beauty of patterns in mathematics. Two questions regarding the pattern of generating NIPTs are noted. (MP)

  18. A Triple Asteroid System

    NASA Astrophysics Data System (ADS)

    2005-09-01

    One of the thousands of minor planets orbiting the Sun has been found to have its own mini planetary system. Astronomer Franck Marchis (University of California, Berkeley) and his colleagues at the Observatoire de Paris have discovered the first triple asteroid system - two small asteroids orbiting a larger one known since 1866 as 87 Sylvia.

  19. Helicobacter pylori eradication with moxifloxacin-containing therapy following failed first-line therapies in South Korea

    PubMed Central

    Kang, Kyu Keun; Lee, Dong Ho; Oh, Dong Hyun; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung; Jung, Hyun Chae

    2014-01-01

    AIM: To investigate moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori (H. pylori) infection following failed first-line treatment. METHODS: The sample included 312 patients for whom first-line treatment failed between January 2008 and May 2013; 27 patients were excluded, and a total of 285 patients received 7- or 14-d moxifloxacin-containing triple therapy as second-line treatment for H. pylori infection. First line regimens included 7-d standard triple (n = 172), 10-d bismuth-containing quadruple (n = 28), 14-d concomitant (n = 37), or 14-d sequential (n = 48) therapy. H. pylori status was evaluated using 13C-urea breath testing 4 wk later, after completion of the treatment. The primary outcome was the H. pylori eradication rate analyzed using intention-to-treat (ITT) and per protocol (PP) analyses. The secondary outcome was the occurrence of serious adverse events. Demographic and clinical factors were analyzed using Student’s t-tests and Pearson’s χ2 tests according to first- and second-line regimens. A P value of less than 0.05 was considered statistically significant. RESULTS: The eradication rate of moxifloxacin-containing triple therapy was 68.4% (ITT; 95%CI: 62.8-73.5) and 73.9% (PP; 95%CI: 68.3-78.8). The eradication rate was significantly higher with 14 d compared to 7 d of treatment (77.5% vs 62.5%, P = 0.017). Peptic ulcer patients had a higher eradication rate than the patients without ulcers (82.9% vs 70.6%, P = 0.046). The demographic and clinical characteristics were not significantly different between the groups according to first-line therapies. ITT and PP analyses of the moxifloxacin-containing triple therapy indicated the following eradication rates: 70.9% (95%CI: 63.8-77.2) and 77.2% (95%CI: 70.1-83.1) for standard triple; 67.9% (95%CI: 51.5-84.2) and 67.9% (95%CI: 51.5-84.2) for bismuth-containing quadruple; 60.4% (95%CI: 46.3-73.0) and 70.7% (95%CI: 54.0-80.9) for sequential; and 67.6% (95%CI: 51

  20. Triple Hit with Drug Carriers: pH- and Temperature-Responsive Theranostics for Multimodal Chemo- and Photothermal Therapy and Diagnostic Applications.

    PubMed

    Baek, Seonmi; Singh, Rajendra K; Kim, Tae-Hyun; Seo, Jae-won; Shin, Ueon Sang; Chrzanowski, Wojciech; Kim, Hae-Won

    2016-04-13

    Currently there is a strong need for new drug delivery systems, which enable targeted and controlled function in delivering drugs while satisfying highly sensitive imaging modality for early detection of the disease symptoms and damaged sites. To meet these criteria we develop a system that integrates therapeutic and diagnostic capabilities (theranostics). Importantly, therapeutic efficacy of the system is enhanced by exploiting synergies between nanoparticles, drug, and hyperthermia. At the core of our innovation is near-infrared (NIR) responsive gold nanorods (Au) coated with drug reservoirs--mesoporous silica shell (mSi)--that is capped with thermoresponsive polymer. Such design of theranostics allows the detection of the system using computed tomography (CT), while finely controlled release of the drug is achieved by external trigger, NIR light irradiation--ON/OFF switch. Doxorubicin (DOX) was loaded into mSi formed on the gold core (Au@mSi-DOX). Pores were then capped with the temperature-sensitive poly(N-isopropylacrylamide)-based N-butyl imidazolium copolymer (poly(NIPAAm-co-BVIm)) resulting in a hybrid system-Au@mSi-DOX@P. A 5 min exposure to NIR induces polymer transition, which triggers the drug release (pores opening), increases local temperature above 43 °C (hyperthermia), and upregulates particle uptake (polymer becomes hydrophilic). The DOX release is also triggered by drop in pH enabling localized drug release when particles are taken up by cancer cells. Importantly, the synergies between chemo- and photothermal therapy for DOX-loaded theranostics were confirmed. Furthermore, higher X-ray attenuation value of the theranostics was confirmed via X-ray CT test indicating that the nanoparticles act as contrast agent and can be detected by CT. PMID:26926826

  1. Triple-functional core-shell structured upconversion luminescent nanoparticles covalently grafted with photosensitizer for luminescent, magnetic resonance imaging and photodynamic therapy in vitro

    NASA Astrophysics Data System (ADS)

    Qiao, Xiao-Fei; Zhou, Jia-Cai; Xiao, Jia-Wen; Wang, Ye-Fu; Sun, Ling-Dong; Yan, Chun-Hua

    2012-07-01

    Upconversion luminescent nanoparticles (UCNPs) have been widely used in many biochemical fields, due to their characteristic large anti-Stokes shifts, narrow emission bands, deep tissue penetration and minimal background interference. UCNPs-derived multifunctional materials that integrate the merits of UCNPs and other functional entities have also attracted extensive attention. Here in this paper we present a core-shell structured nanomaterial, namely, NaGdF4:Yb,Er@CaF2@SiO2-PS, which is multifunctional in the fields of photodynamic therapy (PDT), magnetic resonance imaging (MRI) and fluorescence/luminescence imaging. The NaGdF4:Yb,Er@CaF2 nanophosphors (10 nm in diameter) were prepared via sequential thermolysis, and mesoporous silica was coated as shell layer, in which photosensitizer (PS, hematoporphyrin and silicon phthalocyanine dihydroxide) was covalently grafted. The silica shell improved the dispersibility of hydrophobic PS molecules in aqueous environments, and the covalent linkage stably anchored the PS molecules in the silica shell. Under excitation at 980 nm, the as-fabricated nanomaterial gave luminescence bands at 550 nm and 660 nm. One luminescent peak could be used for fluorescence imaging and the other was suitable for the absorption of PS to generate singlet oxygen for killing cancer cells. The PDT performance was investigated using a singlet oxygen indicator, and was investigated in vitro in HeLa cells using a fluorescent probe. Meanwhile, the nanomaterial displayed low dark cytotoxicity and near-infrared (NIR) image in HeLa cells. Further, benefiting from the paramagnetic Gd3+ ions in the core, the nanomaterial could be used as a contrast agent for magnetic resonance imaging (MRI). Compared with the clinical commercial contrast agent Gd-DTPA, the as-fabricated nanomaterial showed a comparable longitudinal relaxivities value (r1) and similar imaging effect.Upconversion luminescent nanoparticles (UCNPs) have been widely used in many biochemical

  2. Impact of HCV kinetics on treatment outcome differs by the type of real-time HCV assay in NS3/4A protease inhibitor-based triple therapy.

    PubMed

    Ogawa, Eiichi; Furusyo, Norihiro; Murata, Masayuki; Hayashi, Takeo; Shimizu, Motohiro; Mukae, Haru; Toyoda, Kazuhiro; Hotta, Taeko; Uchiumi, Takeshi; Hayashi, Jun

    2016-02-01

    Repeated measurement of the HCV RNA level is essential for properly monitoring treatment efficacy. The aim of this study was to determine the utility of two HCV real-time assays in the evaluation of the impact of hepatitis C virus (HCV) kinetics on the outcome of triple therapy with NS3/4A protease inhibitors (PIs), telaprevir or simeprevir. This study consisted of 171 Japanese patients infected with HCV genotype 1. All 3266 serum samples taken during and post treatment were tested with both the COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HCV Test v2.0 and the Abbott RealTime (ART) HCV Test. Of the 2597 samples undetectable (lower limit of detection [

  3. Safety and efficacy of intensive vs. guideline antiplatelet therapy in high‐risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388)

    PubMed Central

    2015-01-01

    Rationale The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event. Hypothesis Because two antiplatelet agents are superior to one in patients with non‐cardioembolic events, more intensive treatment might be even more effective. Sample size estimates The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance. Methods and design Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one‐month. This international collaborative parallel‐group prospective randomized open‐label blinded‐end‐point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real‐time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation. Study outcome The primary outcome is stroke recurrence and its severity (‘ordinal recurrence’ based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events). Discussion The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One‐third of patients presented with a transient ischemic attack. PMID:26079743

  4. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation.

    PubMed

    Evans, Malkanthi; Rumberger, John A; Azumano, Isao; Napolitano, Joseph J; Citrolo, Danielle; Kamiya, Toshikazu

    2014-01-01

    High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to 16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines. PMID:24600231

  5. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation

    PubMed Central

    Evans, Malkanthi; Rumberger, John A; Azumano, Isao; Napolitano, Joseph J; Citrolo, Danielle; Kamiya, Toshikazu

    2014-01-01

    High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines. PMID:24600231

  6. 17 CFR 270.7d-2 - Definition of “public offering” as used in section 7(d) of the Act with respect to certain...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of âpublic offeringâ as used in section 7(d) of the Act with respect to certain Canadian tax-deferred retirement savings accounts. 270.7d-2 Section 270.7d-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND...

  7. Europa Triple Band

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This picture of Europa, a moon of Jupiter, was obtained on February 20, 1997, by the Solid State Imaging system onboard the Galileo spacecraft during its sixth orbit around Jupiter. The area is centered at 9.3 degrees north latitude, 275.7 degrees west longitude, on the trailing hemisphere of Europa. As Europa moves in its orbit around Jupiter, the trailing hemisphere is the portion which is always on the moon's backside opposite to its direction of motion. The area depicted is about 32 kilometers by 40 kilometers (20 miles by 25 miles). Resolution is 54 meters (59 yards). The Sun illuminates the scene from the right (east).

    A section of a triple band crosses the upper left of the picture and extends for hundreds of miles across the surface. Triple bands derive their name from their appearance at lower resolution as a narrow bright band flanked by a pair of darker bands. At the high resolution of this picture, however, the triple band is much more complex and is composed of a system of ridges 6 kilometers (4 miles) across. Some ridges reach heights of about 180 meters (200 yards). Other features include a hill in the center of the picture about 480 meters (500 yards) high. Two mounds about 6 kilometers across (4 miles) are seen in the bottom of the picture. The ridges, hills and mounds probably all represent uplifts of the icy crust of Europa by processes originating from the interior.

    The Jet Propulsion Laboratory, Pasadena, CA, manages the mission for NASA's Office of Space Science, Washington D.C. This image and other images and data received from Galileo are posted on the World Wide Web Galileo mission home page at: http://galileo.jpl.nasa.gov.

  8. Let-7d miRNA Shows Both Antioncogenic and Oncogenic Functions in Osteosarcoma-Derived 3AB-OS Cancer Stem Cells.

    PubMed

    Di Fiore, Riccardo; Drago-Ferrante, Rosa; Pentimalli, Francesca; Di Marzo, Domenico; Forte, Iris Maria; Carlisi, Daniela; De Blasio, Anna; Tesoriere, Giovanni; Giordano, Antonio; Vento, Renza

    2016-08-01

    Osteosarcoma (OS), an aggressive highly invasive and metastatic bone-malignancy, shows therapy resistance and recurrence, two features that likely depend on cancer stem cells (CSCs), which hold both self-renewing and malignant potential. So, effective anticancer therapies against OS should specifically target and destroy CSCs. We previously found that the let-7d microRNA was downregulated in the 3AB-OS-CSCs, derived from the human OS-MG63 cells. Here, we aimed to assess whether let-7d modulation affected tumorigenic and stemness properties of these OS-CSCs. We found that let-7d-overexpression reduced cell proliferation by decreasing CCND2 and E2F2 cell-cycle-activators and increasing p21 and p27 CDK-inhibitors. Let-7d also decreased sarcosphere-and-colony forming ability, two features associated with self-renewing, and it reduced the expression of stemness genes, including Oct3/4, Sox2, Nanog, Lin28B, and HMGA2. Moreover, let-7d induced mesenchymal-to-epithelial-transition, as shown by both N-Cadherin-E-cadherin-switch and decrease in vimentin. Surprisingly, such switch was accompanied by enhanced migratory/invasive capacities, with a strong increase in MMP9, CXCR4 and VersicanV1. Let-7d- overexpression also reduced cell sensitivity to apoptosis induced by both serum-starvation and various chemotherapy drugs, concomitant with decrease in caspase-3 and increase in BCL2 expression. Our data suggest that let-7d in 3AB-OS-CSCs could induce plastic-transitions from CSCs-to-non-CSCs and vice-versa. To our knowledge this is the first study to comprehensively examine the expression and functions of let-7d in OS-CSCs. By showing that let-7d has both tumor suppressor and oncogenic functions in this context, our findings suggest that, before prospecting new therapeutic strategies based on let-7d modulation, it is urgent to better define its multiple functions. J. Cell. Physiol. 231: 1832-1841, 2016. © 2015 Wiley Periodicals, Inc. PMID:26679758

  9. Teaching Triple Science: GCSE Biology

    ERIC Educational Resources Information Center

    Learning and Skills Network (NJ3), 2007

    2007-01-01

    The Department for Children, Schools and Families (DCSF) has contracted with the Learning and Skills Network to support awareness and take-up of Triple Science GCSEs through the Triple Science Support Programme. This publication provides an introduction to teaching and learning approaches for the extension topics within GCSE Biology. It highlights…

  10. Teaching Triple Science: GCSE Chemistry

    ERIC Educational Resources Information Center

    Learning and Skills Network (NJ3), 2007

    2007-01-01

    The Department for Children, Schools and Families (DCSF) has contracted with the Learning and Skills Network to support awareness and take-up of Triple Science GCSEs through the Triple Science Support Programme. This publication provides an introduction to teaching and learning approaches for the extension topics within GCSE Chemistry. It…

  11. Triple acting radial seal

    DOEpatents

    Ebert, Todd A; Carella, John A

    2012-03-13

    A triple acting radial seal used as an interstage seal assembly in a gas turbine engine, where the seal assembly includes an interstage seal support extending from a stationary inner shroud of a vane ring, the interstage seal support includes a larger annular radial inward facing groove in which an outer annular floating seal assembly is secured for radial displacement, and the outer annular floating seal assembly includes a smaller annular radial inward facing groove in which an inner annular floating seal assembly is secured also for radial displacement. A compliant seal is secured to the inner annular floating seal assembly. The outer annular floating seal assembly encapsulates the inner annular floating seal assembly which is made from a very low alpha material in order to reduce thermal stress.

  12. Triple flames and flame stabilization

    NASA Technical Reports Server (NTRS)

    Broadwell, James E.

    1994-01-01

    It is now well established that when turbulent jet flames are lifted, combustion begins, i.e., the flame is stabilized, at an axial station where the fuel and air are partially premixed. One might expect, therefore, that the beginning of the combustion zone would be a triple flame. Such flames have been described; however, other experiments provide data that are difficult to reconcile with the presence of triple flames. In particular, laser images of CH and OH, marking combustion zones, do not exhibit shapes typical of triple flames, and, more significantly, the lifted flame appears to have a propagation speed that is an order of magnitude higher than the laminar flame speed. The speed of triple flames studied thus far exceeds the laminar value by a factor less than two. The objective of the present task is the resolution of the apparent conflict between the experiments and the triple flame characteristics, and the clarification of the mechanisms controlling flame stability. Being investigated are the resolution achieved in the experiments, the flow field in the neighborhood of the stabilization point, propagation speeds of triple flames, laboratory flame unsteadiness, and the importance of flame ignition limits in the calculation of triple flames that resemble lifted flames.

  13. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice.

    PubMed

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-01

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice. PMID:26771609

  14. Overexpression of PRL7D1 in Leydig Cells Causes Male Reproductive Dysfunction in Mice

    PubMed Central

    Liu, Yaping; Su, Xingyu; Hao, Jie; Chen, Maoxin; Liu, Weijia; Liao, Xiaogang; Li, Gang

    2016-01-01

    Prolactin family 7, subfamily d, member 1 (PRL7D1) is found in mouse placenta. Our recent work showed that PRL7D1 is also present in mouse testis Leydig cells, and the expression of PRL7D1 in the testis exhibits an age-related increase. In the present study, we generated transgenic mice with Leydig cell-specific PRL7D1 overexpression to explore its function during male reproduction. Prl7d1 male mice exhibited subfertility as reflected by reduced sperm counts and litter sizes. The testes from Prl7d1 transgenic mice appeared histologically normal, but the frequency of apoptotic germ cells was increased. Prl7d1 transgenic mice also had lower testosterone concentrations than wild-type mice. Mechanistic studies revealed that Prl7d1 transgenic mice have defects in the testicular expression of steroidogenic acute regulatory protein (STAR) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B). Further studies revealed that PRL7D1 overexpression affected the expression of transferrin (TF) in Sertoli cells. These results suggest that PRL7D1 overexpression could lead to increased germ cell apoptosis and exert an inhibitory effect on testosterone production in Leydig cells by reducing the expression of certain steroidogenic-related genes. In addition, PRL7D1 appears to have important roles in the function of Sertoli cells, which, in turn, affects male fertility. We conclude that the expression level of PRL7D1 is associated with the reproductive function of male mice. PMID:26771609

  15. Optimal triple configurations of stationary shocks

    NASA Astrophysics Data System (ADS)

    Tao, G.; Uskov, V. N.; Chernyshov, M. V.

    Shock-wave systems consisted of three stationary shocks with common (triple) point T (Fig. 1,a-e) are called triple configurations. The slipstream (τ) emanates from the triple point and divides the streams that have gone through the sequence of shocks 1-2 and through the alone (main) shock 3 at another side of the triple point.

  16. Carboxyl pKa Values, Ion Pairs, Hydrogen Bonding, and the pH Dependence of Folding the Hyperthermophile Proteins Sac7d and Sso7d

    PubMed Central

    Clark, Andrew T.; Smith, Kelley; Muhandiram, Ranjith; Edmondson, Stephen P.; Shriver, John W.

    2007-01-01

    Sac7d and Sso7d are homologous, hyperthermophile proteins with a high density of charged surface residues and potential ion pairs. To determine the relative importance of specific amino acid side chains in defining the stability and function of these Archaeal chromatin proteins, pKas were measured for all of the acidic residues in both proteins using 13C NMR chemical shifts. The stability of Sso7d enabled titrations to pH 1 under low salt conditions. Two aspartate residues in Sso7d (D16 and D35) and a single glutamate residue (G54) showed significantly perturbed pKa values in low salt, indicating that the observed pH dependence of stability was primarily due to these three residues. The pH dependence of backbone amide NMR resonances demonstrated that perturbation of all three pKas was primarily the result of side chain-backbone amide hydrogen bonds. Titration data at higher salt for both Sso7d and Sac7d were consistent with this interpretation. Few of the significantly perturbed acidic pKas in Sac7d and Sso7d could be attributed to primarily ion pair or electrostatic interactions. A smaller perturbation of E48 (E47 in Sac7d) was ascribed to an ion pair interaction that may be important in defining the DNA binding surface. The small number (3) of significantly altered pKa values was in good agreement with a linkage analysis of the temperature, pH, and salt dependence of folding. The linkage of the ionization of two or more side chains to protein folding leads to apparent cooperativity in the pH dependence of folding, although each group titrates independently with a Hill coefficient near unity. These results demonstrate that the acid pH dependence of protein stability in these hyperthermophile proteins is due to independent titration of acidic residues with pKas perturbed primarily by hydrogen bonding of the side chain to the backbone. This work demonstrates the need for caution in using structural data alone to argue the importance of ion pairs in stabilizing

  17. Inhibition and Role of let-7d in Idiopathic Pulmonary Fibrosis

    PubMed Central

    Pandit, Kusum V.; Corcoran, David; Yousef, Hanadie; Yarlagadda, Manohar; Tzouvelekis, Argyris; Gibson, Kevin F.; Konishi, Kazuhisa; Yousem, Samuel A.; Singh, Mandal; Handley, Daniel; Richards, Thomas; Selman, Moises; Watkins, Simon C.; Pardo, Annie; Ben-Yehudah, Ahmi; Bouros, Demosthenes; Eickelberg, Oliver; Ray, Prabir; Benos, Panayiotis V.; Kaminski, Naftali

    2010-01-01

    Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually lethal fibrotic lung disease characterized by profound changes in epithelial cell phenotype and fibroblast proliferation. Objectives: To determine changes in expression and role of microRNAs in IPF. Methods: RNA from 10 control and 10 IPF tissues was hybridized on Agilent microRNA microarrays and results were confirmed by quantitative real-time polymerase chain reaction and in situ hybridization. SMAD3 binding to the let-7d promoter was confirmed by chromatin immunoprecipitation, electrophoretic mobility shift assay, luciferase assays, and reduced expression of let-7d in response to transforming growth factor-β. HMGA2, a let-7d target, was localized by immunohistochemistry. In mice, let-7d was inhibited by intratracheal administration of a let-7d antagomir and its effects were determined by immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, and morphometry. Measurements and Main Results: Eighteen microRNAs including let-7d were significantly decreased in IPF. Transforming growth factor-β down-regulated let-7d expression, and SMAD3 binding to the let-7d promoter was demonstrated. Inhibition of let-7d caused increases in mesenchymal markers N-cadherin-2, vimentin, and α-smooth muscle actin (ACTA2) as well as HMGA2 in multiple epithelial cell lines. let-7d was significantly reduced in IPF lungs and the number of epithelial cells expressing let-7d correlated with pulmonary functions. HMGA2 was increased in alveolar epithelial cells of IPF lungs. let-7d inhibition in vivo caused alveolar septal thickening and increases in collagen, ACTA2, and S100A4 expression in SFTPC (pulmonary-associated surfactant protein C) expressing alveolar epithelial cells. Conclusions: Our results indicate a role for microRNAs in IPF. The down-regulation of let-7d in IPF and the profibrotic effects of this down-regulation in vitro and in vivo suggest a key

  18. Probiotics for Standard Triple Helicobacter pylori Eradication

    PubMed Central

    Hauser, Goran; Salkic, Nermin; Vukelic, Karina; JajacKnez, Alenka; Stimac, Davor

    2015-01-01

    Abstract The primary objective in the study is determination of efficacy of probiotic preparation as a supportive therapy in eradication of Helicobacter pylori. The study was multicenter, prospective, randomized, placebo controlled, and double-blind. The subjects first filled out a specially designed questionnaire to assess the severity of the 10 symptoms, which can be related to eradication therapy to be monitored during the trial. Each subject then received 28 capsules of probiotic preparation or matching placebo capsules, which they were supposed to take over the following 14 days, twice a day, at least 2 hours prior to or after the antibiotic therapy administration. A total of 804 patients were enrolled in the trial, of which 650 (80.85%) were included in the analysis. The results show a significantly larger share of cured subjects in the probiotic arm versus the placebo arm (87.38% vs 72.55%; P < 0.001). Additionally, presence and intensity of epigastric pain, bloating, flatulence, taste disturbance, loss of appetite, nausea, vomiting, heartburn, rash, and diarrhea were monitored over the study period. At 15 days postinclusion, probiotic treatment was found superior to placebo in 7 of 10 mentioned symptoms. Average intensity for symptoms potentially related to antibiotic therapy was significantly higher in the placebo group, 0.76 vs 0.55 (P < 0.001). Adding probiotics to the standard triple therapy for H pylori eradication significantly contributes to treatment efficacy and distinctly decreases the adverse effects of therapy and the symptoms of the underlying disease. PMID:25929897

  19. 17 CFR 270.7d-2 - Definition of “public offering” as used in section 7(d) of the Act with respect to certain...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.7d-2 Definition of “public... Canadian law. (3) Eligible Security means a security issued by a Qualified Company that: (i) Is offered to a Participant, or sold to his or her Canadian Retirement Account, in reliance on this section;...

  20. 17 CFR 270.7d-2 - Definition of “public offering” as used in section 7(d) of the Act with respect to certain...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.7d-2 Definition of “public... Canadian law. (3) Eligible Security means a security issued by a Qualified Company that: (i) Is offered to a Participant, or sold to his or her Canadian Retirement Account, in reliance on this section;...

  1. 17 CFR 270.7d-2 - Definition of “public offering” as used in section 7(d) of the Act with respect to certain...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.7d-2 Definition of “public... Canadian law. (3) Eligible Security means a security issued by a Qualified Company that: (i) Is offered to a Participant, or sold to his or her Canadian Retirement Account, in reliance on this section;...

  2. 17 CFR 270.7d-2 - Definition of “public offering” as used in section 7(d) of the Act with respect to certain...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.7d-2 Definition of “public... Canadian law. (3) Eligible Security means a security issued by a Qualified Company that: (i) Is offered to a Participant, or sold to his or her Canadian Retirement Account, in reliance on this section;...

  3. Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation–Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105

    PubMed Central

    Telli, Melinda L.; Jensen, Kristin C.; Vinayak, Shaveta; Kurian, Allison W.; Lipson, Jafi A.; Flaherty, Patrick J.; Timms, Kirsten; Abkevich, Victor; Schackmann, Elizabeth A.; Wapnir, Irene L.; Carlson, Robert W.; Chang, Pei-Jen; Sparano, Joseph A.; Head, Bobbie; Goldstein, Lori J.; Haley, Barbara; Dakhil, Shaker R.; Reid, Julia E.; Hartman, Anne-Renee; Manola, Judith; Ford, James M.

    2015-01-01

    Purpose This study was designed to assess efficacy, safety, and predictors of response to iniparib in combination with gemcitabine and carboplatin in early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. Patients and Methods This single-arm phase II study enrolled patients with stage I to IIIA (T ≥ 1 cm) estrogen receptor–negative (≤ 5%), progesterone receptor–negative (≤ 5%), and human epidermal growth factor receptor 2–negative or BRCA1/2 mutation–associated breast cancer. Neoadjuvant gemcitabine (1,000 mg/m2 intravenously [IV] on days 1 and 8), carboplatin (area under curve of 2 IV on days 1 and 8), and iniparib (5.6 mg/kg IV on days 1, 4, 8, and 11) were administered every 21 days for four cycles, until the protocol was amended to six cycles. The primary end point was pathologic complete response (no invasive carcinoma in breast or axilla). All patients underwent comprehensive BRCA1/2 genotyping, and homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Results Among 80 patients, median age was 48 years; 19 patients (24%) had germline BRCA1 or BRCA2 mutations; clinical stage was I (13%), IIA (36%), IIB (36%), and IIIA (15%). Overall pathologic complete response rate in the intent-to-treat population (n = 80) was 36% (90% CI, 27 to 46). Mean HRD-LOH scores were higher in responders compared with nonresponders (P = .02) and remained significant when BRCA1/2 germline mutations carriers were excluded (P = .021). Conclusion Preoperative combination of gemcitabine, carboplatin, and iniparib is active in the treatment of early-stage triple-negative and BRCA1/2 mutation–associated breast cancer. The HRD-LOH assay was able to identify patients with sporadic triple-negative breast cancer lacking a BRCA1/2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Confirmatory controlled trials are warranted. PMID:25847929

  4. Ficus carica latex prevents invasion through induction of let-7d expression in GBM cell lines.

    PubMed

    Tezcan, Gulcin; Tunca, Berrin; Bekar, Ahmet; Yalcin, Murat; Sahin, Saliha; Budak, Ferah; Cecener, Gulsah; Egeli, Unal; Demir, Cevdet; Guvenc, Gokcen; Yilmaz, Gozde; Erkan, Leman Gizem; Malyer, Hulusi; Taskapilioglu, Mevlut Ozgur; Evrensel, Turkkan; Bilir, Ayhan

    2015-03-01

    Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs and dietary plants has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Ficus carica (fig) latex (FCL) has been determined in a few cancer types, the effect of this latex on GBM tumors has not been investigated. Therefore, in the current study, the anti-proliferative activity of FCL and the effect of the FCL-temozolomide (TMZ) combination were tested in the T98G, U-138 MG, and U-87 MG GBM cell lines using the WST-1 assay. The mechanism of cell death was analyzed using Annexin-V/FITC and TUNEL assays, and the effect of FCL on invasion was tested using the chick chorioallantoic membrane assay. To determine the effect of FCL on GBM progression, the expression levels of 40 GBM associated miRNAs were analyzed in T98G cells using RT-qPCR. According to the obtained data, FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergistically increased in combination with TMZ. In addition, the current study is the first to demonstrate the effect of FCL on modulation of let-7d expression, which may be an important underlying mechanism of the anti-invasive effect of this extract. PMID:25212824

  5. Solution Patterns Predicting Pythagorean Triples

    ERIC Educational Resources Information Center

    Ezenweani, Ugwunna Louis

    2013-01-01

    Pythagoras Theorem is an old mathematical treatise that has traversed the school curricula from secondary to tertiary levels. The patterns it produced are quite interesting that many researchers have tried to generate a kind of predictive approach to identifying triples. Two attempts, namely Diophantine equation and Brahmagupta trapezium presented…

  6. 49 CFR 380.205 - LCV Triples.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 false LCV Triples. 380.205 Section 380.205... REQUIREMENTS LCV Driver-Training Program § 380.205 LCV Triples. (a) To qualify for the training necessary to operate an LCV Triple, a driver-student shall, during the 6 months immediately preceding application...

  7. 49 CFR 380.205 - LCV Triples.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false LCV Triples. 380.205 Section 380.205... REQUIREMENTS LCV Driver-Training Program § 380.205 LCV Triples. (a) To qualify for the training necessary to operate an LCV Triple, a driver-student shall, during the 6 months immediately preceding application...

  8. 49 CFR 380.205 - LCV Triples.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false LCV Triples. 380.205 Section 380.205... REQUIREMENTS LCV Driver-Training Program § 380.205 LCV Triples. (a) To qualify for the training necessary to operate an LCV Triple, a driver-student shall, during the 6 months immediately preceding application...

  9. Triple negative breast cancer: the role of metabolic pathways.

    PubMed

    Dean, S J R; Rhodes, A

    2014-12-01

    The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area. PMID:25500513

  10. Evolution from double to triple-antimalarial drug combinations.

    PubMed

    Shanks, G Dennis; Edstein, Michael D; Jacobus, David

    2015-03-01

    Drug combinations are used to treat multiple-drug resistant malaria parasites and to attempt to further delay the evolution of drug resistance. Most current antimalarial combinations are binary but it is likely that new triple drug combinations will be required in the future. A review of previous triple combinations of antimalarial drugs was done to focus attention on past problems and possible future combinations. The advantages of such triple drug combinations include greater efficacy against multiple-drug resistant strains, synergistic action between the different medications and simplification of the regimen so that it could be administered under direct observation and possibly as single-dose therapy. The disadvantages of poly-pharmacy include increased cost of medication, difficulty preparing robust regulatory packages and problems constructing combined formulations due to drug-drug interactions. Given the arrival of artemisinin tolerance/resistance in Southeast Asia, it is likely that new drugs introduced for malaria treatment will be in triple drug combinations. PMID:25549631

  11. Triple helix purification and sequencing

    DOEpatents

    Wang, R.; Smith, L.M.; Tong, X.E.

    1995-03-28

    Disclosed herein are methods, kits, and equipment for purifying single stranded circular DNA and then using the DNA for DNA sequencing purposes. Templates are provided with an insert having a hybridization region. An elongated oligonucleotide has two regions that are complementary to the insert and the oligo is bound to a magnetic anchor. The oligo hybridizes to the insert on two sides to form a stable triple helix complex. The anchor can then be used to drag the template out of solution using a magnet. The system can purify sequencing templates, and if desired the triple helix complex can be opened up to a double helix so that the oligonucleotide will act as a primer for further DNA synthesis. 4 figures.

  12. Triple helix purification and sequencing

    DOEpatents

    Wang, Renfeng; Smith, Lloyd M.; Tong, Xinchun E.

    1995-01-01

    Disclosed herein are methods, kits, and equipment for purifying single stranded circular DNA and then using the DNA for DNA sequencing purposes. Templates are provided with an insert having a hybridization region. An elongated oligonucleotide has two regions that are complementary to the insert and the oligo is bound to a magnetic anchor. The oligo hybridizes to the insert on two sides to form a stable triple helix complex. The anchor can then be used to drag the template out of solution using a magnet. The system can purify sequencing templates, and if desired the triple helix complex can be opened up to a double helix so that the oligonucleotide will act as a primer for further DNA synthesis.

  13. Antimetastatic Therapies of the Polysulfide Diallyl Trisulfide against Triple-Negative Breast Cancer (TNBC) via Suppressing MMP2/9 by Blocking NF-κB and ERK/MAPK Signaling Pathways

    PubMed Central

    Wang, Yingyu; Wei, Zhonghong; Tao, Li; Zhu, Zhijie; Sheng, Xiaobo; Wang, Siliang; Ruan, Junshan; Liu, Zhaoguo; Cao, Yuzhu; Shan, Yunlong; Sun, Lihua; Wang, Aiyun; Chen, Wenxing; Lu, Yin

    2015-01-01

    Background Migration and invasion are two crucial steps of tumor metastasis. Blockage of these steps may be an effective strategy to reduce the risk. The objective of the present study was to investigate the effects of diallyl trisulfide (DATS), a natural organosulfuric compound with most sulfur atoms found in garlic, on migration and invasion in triple negative breast cancer (TNBC) cells. Molecular mechanisms underlying the anticancer effects of DATS were further investigated. Methods and Results MDA-MB-231 cells and HS 578t breast cancer cells were treated with different concentrations of DATS. DATS obviously suppressed the migration and invasion of two cell lines and changed the morphological. Moreover, DATS inhibited the mRNA/protein/ enzymes activities of MMP2/9 via attenuating the NF-κB pathway. DATS also inhibited ERK/MAPK rather than p38 and JNK. Conclusion DATS inhibits MMP2/9 activity and the metastasis of TNBC cells, and emerges as a potential anti-cancer agent. The inhibitory effects are associated with down-regulation of the transcriptional activities of NF-κB and ERK/MAPK signaling pathways. PMID:25927362

  14. SOLTI NeoPARP: a phase II randomized study of two schedules of iniparib plus paclitaxel versus paclitaxel alone as neoadjuvant therapy in patients with triple-negative breast cancer.

    PubMed

    Llombart-Cussac, Antonio; Bermejo, Begoña; Villanueva, Cristian; Delaloge, Suzette; Morales, Serafín; Balmaña, Judith; Amillano, Kepa; Bonnefoi, Hervé; Casas, Ana; Manso, Luis; Roché, Henri; Gonzalez-Santiago, Santiago; Gavilá, Joaquín; Sánchez-Rovira, Pedro; Di Cosimo, Serena; Harbeck, Nadia; Charpentier, Eric; Garcia-Ribas, Ignacio; Radosevic-Robin, Nina; Aura, Claudia; Baselga, Jose

    2015-11-01

    Iniparib is an investigational agent with antitumor activity of controversial mechanism of action. Two previous trials in advanced triple-negative breast cancer (TNBC) in combination with gemcitabine and carboplatin showed some evidence of efficacy that was not confirmed. This phase II randomized neoadjuvant study was designed to explore its activity and tolerability with weekly paclitaxel (PTX) as neoadjuvant treatment in TNBC patients. 141 patients with Stage II-IIIA TNBC were randomly assigned to receive PTX (80 mg/m(2), d1; n = 47) alone or in combination with iniparib, either once-weekly (PWI) (11.2 mg/kg, d1; n = 46) or twice-weekly (PTI) (5.6 mg/kg, d1, 4; n = 48) for 12 weeks. Primary endpoint was pathologic complete response (pCR) in the breast. pCR rate was similar among the three arms (21, 22, and 19 % for PTX, PWI, and PTI, respectively). Secondary efficacy endpoints were comparable: pCR in breast and axilla (21, 17, and 19 %); best overall response in the breast (60, 61, and 63 %); and breast conservation rate (53, 54, and 50 %). Slightly more patients in the PTI arm presented grade 3/4 neutropenia (4, 0, and 10 %). Grade 1/2 (28, 22, and 29 %), but no grade 3/4 neuropathy, was observed. There were no differences in serious adverse events and treatment-emergent adverse events leading to treatment discontinuation among the three arms. Addition of iniparib to weekly PTX did not add relevant antitumor activity or toxicity. These results do not support further evaluation of the combination of iniparib at these doses plus paclitaxel in early TNBC. PMID:26536871

  15. Energy Efficient Triple IG Automation EEE (Triple-E)

    SciTech Connect

    McGlinchy, Timothy B

    2013-02-28

    GED Integrated Solutions collaborated with US window and door manufactures to investigate, design and verify technical and cost feasibility for producing high performance, high volume, low material and labor cost window, utilizing a modified window design containing a triple insulating glass unit (IGU). This window design approach when combined with a high volume IGU manufacturing system, can produce R5 rated windows for an approximate additional consumer cost of only $4 per square foot when compared to conventional Low-E argon dual pane IG windows, resulting in a verify practical, reliable and affordable high performance window for public use.

  16. The mystery of let-7d - a small RNA with great power.

    PubMed

    Kolenda, Tomasz; Przybyła, Weronika; Teresiak, Anna; Mackiewicz, Andrzej; Lamperska, Katarzyna M

    2014-01-01

    miRNAs belong to a class of small non-coding RNAs which can modulate gene expression. Disturbances in their expression and function may cause cancer formation, progression and cell response to various types of stress. The let-7 family is one of the most studied groups of miRNAs. The family contains 13 members with similar sequences and a wide spectrum of target genes. In this paper, we mostly focus on one member of the family - let-7d. This miRNA is dysregulated in many types of cancers. It can be over- or down-expressed, and it acts as a tumor suppressor or oncogene. It regulates various genes such as LIN28, C-MYC, K-RAS, HMGA2 and IMP-1. Moreover, let-7d has a significant impact on epithelial-to-mesenchymal transition (EMT) and formation of cancer initiating cells which are resistant to irradiation and chemical exposure and responsible for cancer metastasis. Let-7d can serve as a prognostic and predictive marker for personalization of the treatment. Let-7d is a small RNA with great power, but in different cell genetic backgrounds it acts in different ways, which makes this molecule still mysterious. PMID:25477749

  17. Severe Infections with Human Adenovirus 7d in 2 Adults in Family, Illinois, USA, 2014

    PubMed Central

    Ison, Michael G.

    2016-01-01

    Human adenovirus 7d, a genomic variant with no reported circulation in the United States, was isolated from 2 adults with severe respiratory infections in Illinois. Molecular typing identified a close relationship with strains of the same genome type isolated from cases of respiratory disease in several provinces of China since 2009. PMID:26982199

  18. The Sinai triple junction revisited

    NASA Astrophysics Data System (ADS)

    Courtillot, Vincent; Armijo, Rolando; Tapponnier, Paul

    1987-09-01

    This paper is a summary of a more detailed analysis of the kinematics of the Sinai triple junction (Courtillot et al., 1987). Accurate kinematic data are lacking along the Red Sea and they can be supplemented by bathymetric, topographic and geological data pertaining to the three arms of the entirely continental Sinai triple junction. Motions across the northern Red Sea and along the Gulf of Elat are an order of magnitude larger than across the Gulf of Suez. The direction of motion there remains a major uncertainty. A possible kinematic model is highlighted, in which right-lateral strike-slip motion and small pull-apart basins occur along the Gulf of Suez, in agreement with recent field observations in Egypt. Early Miocene is marked by major geodynamical changes all along the northern boundaries of the African and Indian plates. We suggest that rifting in the Arabian Sea, Gulf of Aden, Red Sea and Gulf of Suez was initiated at the end of the first phase of continental extrusion of Indochina, when the Tibetan plateau began to rise and spreading in the South China Sea came to a halt.

  19. NIM Realization of the Gallium Triple Point

    NASA Astrophysics Data System (ADS)

    Xiaoke, Yan; Ping, Qiu; Yuning, Duan; Yongmei, Qu

    2003-09-01

    In the last three years (1999 to 2001), the gallium triple-point cell has been successfully developed, and much corresponding research has been carried out at the National Institute of Metrology (NIM), Beijing, China. This paper presents the cell design, apparatus and procedure for realizing the gallium triple point, and presents studies on the different freezing methods. The reproducibility is 0.03 mK, and the expanded uncertainty of realization of the gallium triple point is evaluated to be 0.17 mK (p=0.99, k=2.9). Also, the reproducibility of the gallium triple point was compared with that of the triple point of water.

  20. Regulation of PBX3 expression by androgen and Let-7d in prostate cancer

    PubMed Central

    2011-01-01

    Background The pre-leukemia transcription factor 3 (PBX) is part of the PBX family of transcription factors, which is known to regulate genes involved in differentiation of urogenital organs and steroidogenesis. This is of interest with regard to prostate cancer progression as regulation of steroidogenesis is one of the mechanisms involved in the development of castration-resistant prostate cancer. In light of this we wanted to investigate the possible involvement of androgen regulation of PBX3 expression in prostate cancer. Results In this study, we show that PBX3 is post-transcriptionally regulated by androgen in prostate cancer cells and that the effect might be independent of the androgen receptor. Furthermore, PBX3 was identified as a target of Let-7d, an androgen regulated microRNA. Let-7d was down-regulated in malignant compared to benign prostate tissue, whereas up-regulation of PBX3 expression was observed. Conclusions We demonstrate that PBX3 is up-regulated in prostate cancer and post- transcriptionally regulated by androgen through Let-7d. PMID:21548940

  1. Cocaine modulates the expression of opioid receptors and miR-let-7d in zebrafish embryos.

    PubMed

    López-Bellido, Roger; Barreto-Valer, Katherine; Sánchez-Simón, Fátima Macho; Rodríguez, Raquel E

    2012-01-01

    Prenatal exposure to cocaine, in mammals, has been shown to interfere with the expression of opioid receptors, which can have repercussions in its activity. Likewise, microRNAs, such as let-7, have been shown to regulate the expression of opioid receptors and hence their functions in mammals and in vitro experiments. In light of this, using the zebrafish embryos as a model our aim here was to evaluate the actions of cocaine in the expression of opioid receptors and let-7d miRNA during embryogenesis. In order to determine the effects produced by cocaine on the opioid receptors (zfmor, zfdor1 and zfdor2) and let-7d miRNA (dre-let-7d) and its precursors (dre-let-7d-1 and dre-let-7d-2), embryos were exposed to 1.5 µM cocaine hydrochloride (HCl). Our results revealed that cocaine upregulated dre-let-7d and its precursors, and also increased the expression of zfmor, zfdor1 and zfdor2 during early developmental stages and decreased them in late embryonic stages. The changes observed in the expression of opioid receptors might occur through dre-let-7d, since DNA sequences and the morpholinos of opioid receptors microinjections altered the expression of dre-let-7d and its precursors. Likewise, opioid receptors and dre-let-7d showed similar distributions in the central nervous system (CNS) and at the periphery, pointing to a possible interrelationship between them.In conclusion, the silencing and overexpression of opioid receptors altered the expression of dre-let-7d, which points to the notion that cocaine via dre-let-7 can modulate the expression of opioid receptors. Our study provides new insights into the actions of cocaine during zebrafish embryogenesis, indicating a role of miRNAs, let-7d, in development and its relationship with gene expression of opioid receptors, related to pain and addiction process. PMID:23226419

  2. Cocaine Modulates the Expression of Opioid Receptors and miR-let-7d in Zebrafish Embryos

    PubMed Central

    López-Bellido, Roger; Barreto-Valer, Katherine; Sánchez-Simón, Fátima Macho; Rodríguez, Raquel E.

    2012-01-01

    Prenatal exposure to cocaine, in mammals, has been shown to interfere with the expression of opioid receptors, which can have repercussions in its activity. Likewise, microRNAs, such as let-7, have been shown to regulate the expression of opioid receptors and hence their functions in mammals and in vitro experiments. In light of this, using the zebrafish embryos as a model our aim here was to evaluate the actions of cocaine in the expression of opioid receptors and let-7d miRNA during embryogenesis. In order to determine the effects produced by cocaine on the opioid receptors (zfmor, zfdor1 and zfdor2) and let-7d miRNA (dre-let-7d) and its precursors (dre-let-7d-1 and dre-let-7d-2), embryos were exposed to 1.5 µM cocaine hydrochloride (HCl). Our results revealed that cocaine upregulated dre-let-7d and its precursors, and also increased the expression of zfmor, zfdor1 and zfdor2 during early developmental stages and decreased them in late embryonic stages. The changes observed in the expression of opioid receptors might occur through dre-let-7d, since DNA sequences and the morpholinos of opioid receptors microinjections altered the expression of dre-let-7d and its precursors. Likewise, opioid receptors and dre-let-7d showed similar distributions in the central nervous system (CNS) and at the periphery, pointing to a possible interrelationship between them. In conclusion, the silencing and overexpression of opioid receptors altered the expression of dre-let-7d, which points to the notion that cocaine via dre-let-7 can modulate the expression of opioid receptors. Our study provides new insights into the actions of cocaine during zebrafish embryogenesis, indicating a role of miRNAs, let-7d, in development and its relationship with gene expression of opioid receptors, related to pain and addiction process. PMID:23226419

  3. Simulation of triple coincidences in PET.

    PubMed

    Cal-González, J; Lage, E; Herranz, E; Vicente, E; Udias, J M; Moore, S C; Park, M-A; Dave, S R; Parot, V; Herraiz, J L

    2015-01-01

    Although current PET scanners are designed and optimized to detect double coincidence events, there is a significant amount of triple coincidences in any PET acquisition. Triple coincidences may arise from causes such as: inter-detector scatter (IDS), random triple interactions (RT), or the detection of prompt gamma rays in coincidence with annihilation photons when non-pure positron-emitting radionuclides are used (β(+)γ events). Depending on the data acquisition settings of the PET scanner, these triple events are discarded or processed as a set of double coincidences if the energy of the three detected events is within the scanner's energy window. This latter option introduces noise in the data, as at most, only one of the possible lines-of-response defined by triple interactions corresponds to the line along which the decay occurred. Several novel works have pointed out the possibility of using triple events to increase the sensitivity of PET scanners or to expand PET imaging capabilities by allowing differentiation between radiotracers labeled with non-pure and pure positron-emitting radionuclides. In this work, we extended the Monte Carlo simulator PeneloPET to assess the proportion of triple coincidences in PET acquisitions and to evaluate their possible applications. We validated the results of the simulator against experimental data acquired with a modified version of a commercial preclinical PET/CT scanner, which was enabled to acquire and process triple-coincidence events. We used as figures of merit the energy spectra for double and triple coincidences and the triples-to-doubles ratio for different energy windows and radionuclides. After validation, the simulator was used to predict the relative quantity of triple-coincidence events in two clinical scanners assuming different acquisition settings. Good agreement between simulations and preclinical experiments was found, with differences below 10% for most of the observables considered. For clinical

  4. Triple flame structure and diffusion flame stabilization

    NASA Technical Reports Server (NTRS)

    Veynante, D.; Vervisch, L.; Poinsot, T.; Linan, A.; Ruetsch, G.

    1994-01-01

    The stabilization of diffusion flames is studied using asymptotic techniques and numerical tools. The configuration studied corresponds to parallel streams of cold oxidizer and fuel initially separated by a splitter plate. It is shown that stabilization of a diffusion flame may only occur in this situation by two processes. First, the flame may be stabilized behind the flame holder in the wake of the splitter plate. For this case, numerical simulations confirm scalings previously predicted by asymptotic analysis. Second, the flame may be lifted. In this case a triple flame is found at longer distances downstream of the flame holder. The structure and propagation speed of this flame are studied by using an actively controlled numerical technique in which the triple flame is tracked in its own reference frame. It is then possible to investigate the triple flame structure and velocity. It is shown, as suggested from asymptotic analysis, that heat release may induce displacement speeds of the triple flame larger than the laminar flame speed corresponding to the stoichiometric conditions prevailing in the mixture approaching the triple flame. In addition to studying the characteristics of triple flames in a uniform flow, their resistance to turbulence is investigated by subjecting triple flames to different vortical configurations.

  5. Triple point of Yukawa systems

    NASA Astrophysics Data System (ADS)

    Hamaguchi, S.; Farouki, R. T.; Dubin, D. H. E.

    1997-10-01

    The molecular dynamics simulations of Yukawa (i.e., screened-Coulomb) systems that were applied to the regime of weak screening in an earlier study [S. Hamaguchi, R. T. Farouki, and D. H. E. Dubin, J. Chem. Phys. 105, 7641 (1996)] are extended to the strong screening regime. Transition temperatures at the fluid-solid phase boundary and the solid-solid phase boundary are obtained as functions of the screening parameter κ=a/λD (i.e., the ratio of the Wigner-Seitz radius a to the Debye length λD). The resulting phase diagram also covers the triple point-the intersection of the fluid-solid and solid-solid phase boundaries-at κ=4.28 and Γ=5.6×103, where Γ is the ratio of the Coulomb potential energy to the kinetic energy per particle (i.e., Γ=Q2/4πɛ0akT, where Q is the charge of each Yukawa particle and T is the system temperature). Yukawa systems serve as models for plasmas and colloidal suspensions of charged particulates.

  6. Triple-effect absorption chiller cycles

    SciTech Connect

    DeVault, R.C.; Grossman, G.

    1992-06-01

    Gas-fired absorption chillers are widely used for air-conditioning buildings. Even the highest efficiency double-effect absorption chillers used more primary energy for air-conditioning buildings than the better electric chillers. Two different triple-effect absorption chiller cycles are capable of substantial performance improvement over equivalent double-effect cycles. One cycle uses two condensers and two absorbers to achieve the ``triple effect.`` A second cycle, the Double-Condenser Coupled Triple-Effect, uses three condensers as well as a third condenser subcooler (which exchanges heat with the lowest temperature first-effect generator). These triple-effect absorption cycles have the potential to be as energy efficient (on a primary fuel basis) as the best electric chillers. 19 refs.

  7. Triple-effect absorption chiller cycles

    SciTech Connect

    DeVault, R.C. ); Grossman, G. )

    1992-01-01

    Gas-fired absorption chillers are widely used for air-conditioning buildings. Even the highest efficiency double-effect absorption chillers used more primary energy for air-conditioning buildings than the better electric chillers. Two different triple-effect absorption chiller cycles are capable of substantial performance improvement over equivalent double-effect cycles. One cycle uses two condensers and two absorbers to achieve the triple effect.'' A second cycle, the Double-Condenser Coupled Triple-Effect, uses three condensers as well as a third condenser subcooler (which exchanges heat with the lowest temperature first-effect generator). These triple-effect absorption cycles have the potential to be as energy efficient (on a primary fuel basis) as the best electric chillers. 19 refs.

  8. On the Triple Interacting Dark Energy Model

    NASA Astrophysics Data System (ADS)

    Huang, Peng; Huang, Yong-Chang

    2013-07-01

    Three aspects of the triple interacting dark energy model are studied. The relation between two types of the triple interacting dark energy models is investigated first. Then, the concrete forms of the interacting terms are given by supposing ratios between different energy components is stationary. Furthermore, the stability of the triple interacting dark energy model with different transfer terms is studied in detail, and the complete table of relations between the stability and the transfer terms is given, we find that only models with transformation between matter and dark energy proportional to ρc or ρDE, while the transformation between radiation and matter is not proportional to ρR, are stable against perturbation, which give strong restriction on the model building of the triple interacting.

  9. Arthroscopic Subtalar, Double, and Triple Fusion.

    PubMed

    Walter, Richard; Parsons, Stephen; Winson, Ian

    2016-09-01

    Arthroscopic approaches to subtalar, double, and triple arthrodesis allow relative preservation of the soft tissue envelope compared with traditional open approaches. The surgical technique involving the use of a 4.5-mm 30° arthroscope via sinus tarsi portals is described. All 3 joints of the triple joint can be prepared for fusion with motorized burrs. Rigid fixation is achieved with cannulated screws. High union rates and low complication rates have been reported. PMID:27524712

  10. Reliability and Validity of a Domain-Specific Last 7-d Sedentary Time Questionnaire

    PubMed Central

    WIJNDAELE, KATRIEN; DE BOURDEAUDHUIJ, ILSE; GODINO, JOB G.; LYNCH, BRIGID M.; GRIFFIN, SIMON J.; WESTGATE, KATE; BRAGE, SØREN

    2014-01-01

    ABSTRACT Purpose The objective of this study is to examine test–retest reliability, criterion validity, and absolute agreement of a self-report, last 7-d sedentary behavior questionnaire (SIT-Q-7d), which assesses total daily sedentary time as an aggregate of sitting/lying down in five domains (meals, transportation, occupation, nonoccupational screen time, and other sedentary time). Dutch (DQ) and English (EQ) versions of the questionnaire were examined. Methods Fifty-one Flemish adults (ages 39.4 ± 11.1 yr) wore a thigh accelerometer (activPAL3™) and simultaneously kept a domain log for 7 d. The DQ was subsequently completed twice (median test–retest interval: 3.3 wk). Thigh-acceleration sedentary time was log annotated to create comparable domain-specific and total sedentary time variables. Four hundred two English adults (ages 49.6 ± 7.3 yr) wore a combined accelerometer and HR monitor (Actiheart®) for 6 d to objectively measure total sedentary time. The EQ was subsequently completed twice (median test–retest interval: 3.4 wk). In both samples, the questionnaire reference frame overlapped with the criterion measure administration period. All participants had five or more valid days of criterion data, including one or more weekend day. Results Test–retest reliability (intraclass correlation coefficient (95% CI)) was fair to good for total sedentary time (DQ: 0.68 (0.50–0.81); EQ: 0.53 (0.44–0.62)) and poor to excellent for domain-specific sedentary time (DQ: from 0.36 (0.10–0.57) (meals) to 0.66 (0.46–0.79) (occupation); EQ: from 0.45 (0.35–0.54) (other sedentary time) to 0.76 (0.71–0.81) (meals)). For criterion validity (Spearman rho), significant correlations were found for total sedentary time (DQ: 0.52; EQ: 0.22; all P <0.001). Compared with domain-specific criterion variables (DQ), modest-to-strong correlations were found for domain-specific sedentary time (from 0.21 (meals) to 0.76 (P < 0.001) (screen time)). The questionnaire

  11. The von Neumann Triple Point Paradox

    NASA Astrophysics Data System (ADS)

    Sanders, Richard; Tesdall, Allen M.

    We describe the problem of weak shock reflection off a wedge and discuss the triple point paradox that arises. When the shock is sufficiently weak and the wedge is thin, Mach reflection appears to be observed but is impossible according to what von Neumann originally showed in 1943. We summarize some recent numerical results for weak shock reflection problems for the unsteady transonic small disturbance equations, the nonlinear wave system, and the Euler equations. Rather than finding a standard but mathematically inadmissible Mach reflection with a shock triple point, the solutions contain a complex structure: there is a sequence of triple points and supersonic patches in a tiny region behind the leading triple point, with an expansion fan originating at each triple point. The sequence of patches may be infinite, and we refer to this structure as Guderley Mach reflection. The presence of the expansion fans at the triple points resolves the paradox. We describe some recent experimental evidence which is consistent with these numerical findings.

  12. Concepts and targets in triple-negative breast cancer: recent results and clinical implications.

    PubMed

    Saha, Poornima; Nanda, Rita

    2016-09-01

    Triple-negative breast cancer (TNBC) is a heterogeneous disease in which tumors are defined by lack of expression of the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) receptor. No targeted therapies are available for the treatment of TNBC, and chemotherapy remains the standard of care. Gene expression profiling has identified six distinct molecular subtypes of TNBC. The identification of novel targets, coupled with the development of therapies for different subsets of TNBC, holds great promise for the future treatment of this aggressive form of breast cancer. This review focuses on novel therapies in development for the treatment of TNBC. PMID:27583027

  13. Concepts and targets in triple-negative breast cancer: recent results and clinical implications

    PubMed Central

    Saha, Poornima; Nanda, Rita

    2016-01-01

    Triple-negative breast cancer (TNBC) is a heterogeneous disease in which tumors are defined by lack of expression of the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) receptor. No targeted therapies are available for the treatment of TNBC, and chemotherapy remains the standard of care. Gene expression profiling has identified six distinct molecular subtypes of TNBC. The identification of novel targets, coupled with the development of therapies for different subsets of TNBC, holds great promise for the future treatment of this aggressive form of breast cancer. This review focuses on novel therapies in development for the treatment of TNBC. PMID:27583027

  14. Recombination induced by triple-helix-targeted DNA damage in mammalian cells.

    PubMed Central

    Faruqi, A F; Seidman, M M; Segal, D J; Carroll, D; Glazer, P M

    1996-01-01

    Gene therapy has been hindered by the low frequency of homologous recombination in mammalian cells. To stimulate recombination, we investigated the use of triple-helix-forming oligonucleotides (TFOs) to target DNA damage to a selected site within cells. By treating cells with TFOs linked to psoralen, recombination was induced within a simian virus 40 vector carrying two mutant copies of the supF tRNA reporter gene. Gene conversion events, as well as mutations at the target site, were also observed. The variety of products suggests that multiple cellular pathways can act on the targeted damage, and data showing that the triple helix can influence these pathways are presented. The ability to specifically induce recombination or gene conversion within mammalian cells by using TFOs may provide a new research tool and may eventually lead to novel applications in gene therapy. PMID:8943337

  15. Structure and morphology of a triple point

    NASA Astrophysics Data System (ADS)

    Hekiri, H.; Emanuel, G.

    2015-05-01

    A comprehensive analytical/numerical treatment of triple points is based on over 5 × 103 parametric solutions. The approach is applicable to triple points in steady or unsteady, three-dimensional flow with a variable freestream. The analysis is for a perfect gas with three different ratios of specific heat values and an upstream Mach number that ranges from an onset value to 10. The structure and morphology of the solution manifold is extensively discussed. This includes solution type, solution overlap, double, triple, and split solutions, shock wave and slipstream angular orientations, the strength of the shocks, etc. Both the reflected and Mach stem shocks can be normal shocks. The occurrence, conditions, and parametric results for these normal shocks are provided.

  16. Drop evaporation and triple line dynamics

    NASA Astrophysics Data System (ADS)

    Sobac, Benjamin; Brutin, David; Gavillet, Jerome; Université de Provence Team; Cea Liten Team

    2011-03-01

    Sessile drop evaporation is a phenomenon commonly came across in nature or in industry with cooling, paintings or DNA mapping. However, the evaporation of a drop deposited on a substrate is not completely understood due to the complexity of the problem. Here we investigate, with several nano-coating of the substrate (PTFE, SiOx, SiOc and CF), the influence of the dynamic of the triple line on the evaporation process. The experiment consists in analyzing simultaneously the motion of the triple line, the kinetics of evaporation, the internal thermal motion and the heat and mass transfer. Measurements of temperature, heat-flux and visualizations with visible and infrared cameras are performed. The dynamics of the evaporative heat flux appears clearly different depending of the motion of the triple line

  17. Therapeutic targets of triple-negative breast cancer: a review.

    PubMed

    Jamdade, Vinayak S; Sethi, Nikunj; Mundhe, Nitin A; Kumar, Parveen; Lahkar, Mangala; Sinha, Neeraj

    2015-09-01

    Breast cancer (BC) is the second most common cause of cancer deaths. Triple-negative breast cancer (TNBC) does not show immunohistochemical expression of oestrogen receptors, progesterone receptors or HER2. At present, no suitable treatment option is available for patients with TNBC. This dearth of effective conventional therapies for the treatment of advanced stage breast cancer has provoked the development of novel strategies for the management of patients with TNBC. This review presents recent information associated with different therapeutic options for the treatment of TNBC focusing on promising targets such as the Notch signalling, Wnt/β-catenin and Hedgehog pathways, in addition to EGFR, PARP1, mTOR, TGF-β and angiogenesis inhibitors. PMID:26040571

  18. Preliminary Measurements of the Xenon Triple Point

    NASA Astrophysics Data System (ADS)

    Steur, P. P. M.; Giraudi, D.

    2014-04-01

    Ever since the construction and definition of the highly successful International Temperature Scale of 1990 (ITS-90), one severe deficiency of the scale has been recognized, without a reliable remedy. The problem is the fact that the only then available high-quality fixed point between the argon triple point and the water triple point was the mercury triple point, which unfortunately is situated rather closely to the water triple point, thus having an extremely strong influence on the interpolation function of SPRTs in the range. Already before 1990, measurements on possible fixed points better placed in this temperature range have been investigated, such as the triple points of krypton and xenon. However, results have been rather elusive, mainly regarding the rather large melting range of their transition. A turning point was the 2005 paper from the National Research Council (NRC, Canada), where it was established that the relatively high content of krypton was the culprit for the large melting range of the xenon transitions published previously. Indeed, measurements on a xenon sample with very low krypton content produced a very high-quality plateau, of the same level as other ITS-90 fixed points. However, no follow-up measurements have been reported, and thus neither have comparison measurements been reported. Shortly, after the appearance of the NRC paper, Istituto Nazionale di Ricerca Metrologica (INRIM, Italy) acquired a batch of the same high-purity xenon as used by NRC with the aim of preparing a few sealed cells with it and trying to reproduce the NRC results. However, with the start of the Neon Project (Euromet Project 770), the realization of these intentions had to be postponed until now. Last December, three cells of different design have been filled with this high-quality xenon and preliminary results of the measurements on the triple point are reported.

  19. The triple point of sulfur hexafluoride

    NASA Astrophysics Data System (ADS)

    Rourke, P. M. C.

    2016-04-01

    A cryogenic fixed point cell has been filled with high purity (99.999%) sulfur hexafluoride (SF6) and measured in an adiabatic closed-cycle cryostat system. Temperature measurements of the SF6 melting curve were performed using a capsule-type standard platinum resistance thermometer (CSPRT) calibrated over the International Temperature Scale of 1990 (ITS-90) subrange from the triple point of equilibrium hydrogen to the triple point of water. The measured temperatures were corrected by 0.37 mK for the effects of thermometer self-heating, and the liquidus-point temperature estimated by extrapolation to melted fraction F  =  1 of a simple linear regression versus melted fraction F in the range F  =  0.53 to 0.84. Based on this measurement, the temperature of the triple point of sulfur hexafluoride is shown to be 223.555 23(49) K (k  =  1) on the ITS-90. This value is in excellent agreement with the best prior measurements reported in the literature, but with considerably smaller uncertainty. An analysis of the detailed uncertainty budget of this measurement suggests that if the triple point of sulfur hexafluoride were to be included as a defining fixed point of the next revision of the International Temperature Scale, it could do so with a total realization uncertainty of approximately 0.43 mK, slightly larger than the realization uncertainties of the defining fixed points of the ITS-90. Since the combined standard uncertainty of this SF6 triple point temperature determination is dominated by chemical impurity effects, further research exploring gas purification techniques and the influence of specific impurity species on the SF6 triple point temperature may bring the realization uncertainty of SF6 as a fixed point material into the range of the defining fixed points of the ITS-90.

  20. Triple-negative breast cancer: treatment challenges and solutions

    PubMed Central

    Collignon, Joëlle; Lousberg, Laurence; Schroeder, Hélène; Jerusalem, Guy

    2016-01-01

    Triple-negative breast cancers (TNBCs) are defined by the absence of estrogen and progesterone receptors and the absence of HER2 overexpression. These cancers represent a heterogeneous breast cancer subtype with a poor prognosis. Few systemic treatment options exist besides the use of chemotherapy (CT). The heterogeneity of the disease has limited the successful development of targeted therapy in unselected patient populations. Currently, there are no approved targeted therapies for TNBC. However, intense research is ongoing to identify specific targets and develop additional and better systemic treatment options. Standard adjuvant and neoadjuvant regimens include anthracyclines, cyclophosphamide, and taxanes. Platinum-based CT has been proposed as another CT option of interest in TNBC. We review the role of this therapy in general, and particularly in patients carrying BRCA germ-line mutations. Available data concerning the role of platinum-based CT in TNBC were acquired primarily in the neoadjuvant setting. The routine use of platinum-based CT is not yet recommended by available guidelines. Many studies have reported the molecular characterization of TNBCs. Several actionable targets have been identified. Novel therapeutic strategies are currently being tested in clinical trials based on promising results observed in preclinical studies. These targets include androgen receptor, EGFR, PARP, FGFR, and the angiogenic pathway. We review the recent data on experimental drugs in this field. We also discuss the recent data concerning immunologic checkpoint inhibitors. PMID:27284266

  1. Phage display selection of tight specific binding variants from a hyperthermostable Sso7d scaffold protein library.

    PubMed

    Zhao, Ning; Schmitt, Margaret A; Fisk, John D

    2016-04-01

    Antibodies, the quintessential biological recognition molecules, are not ideal for many applications because of their large size, complex modifications, and thermal and chemical instability. Identifying alternative scaffolds that may be evolved into tight, specific binding molecules with improved physical properties is of increasing interest, particularly for biomedical applications in resource-limited environments. Hyperthermophilic organisms, such as Sulfolobus solfataricus, are an attractive source of highly stable proteins that may serve as starting points for alternative molecular recognition scaffolds. We describe the first application of phage display to identify binding proteins based on the S. solfataricus protein Sso7d scaffold. Sso7d is a small cysteine-free DNA-binding protein (approximately 7 kDa, 63 amino acids), with a melting temperature of nearly 100 °C. Tight-binding Sso7d variants were selected for a diverse set of protein targets from a 10(10) member library, demonstrating the versatility of the scaffold. These Sso7d variants are able to discriminate among closely related human, bovine and rabbit serum albumins. Equilibrium dissociation constants in the nanomolar to low micromolar range were measured via competitive ELISA. Importantly, the Sso7d variants continue to bind their targets in the absence of the phage context. Furthermore, phage-displayed Sso7d variants retain their binding affinity after exposure to temperatures up to 70 °C. Taken together, our results suggest that the Sso7d scaffold will be a complementary addition to the range of non-antibody scaffold proteins that may be utilized in phage display. Variants of hyperthermostable binding proteins have potential applications in diagnostics and therapeutics for environments with extreme conditions of storage and deployment. PMID:26835881

  2. MicroRNA let-7d is a target of cannabinoid CB1 receptor and controls cannabinoid signaling.

    PubMed

    Chiarlone, Anna; Börner, Christine; Martín-Gómez, Laura; Jiménez-González, Ada; García-Concejo, Adrián; García-Bermejo, María L; Lorente, Mar; Blázquez, Cristina; García-Taboada, Elena; de Haro, Amador; Martella, Elisa; Höllt, Volker; Rodríguez, Raquel; Galve-Roperh, Ismael; Kraus, Jürgen; Guzmán, Manuel

    2016-09-01

    Cannabinoid CB1 receptor, the molecular target of endocannabinoids and cannabis active components, is one of the most abundant metabotropic receptors in the brain. Cannabis is widely used for both recreational and medicinal purposes. Despite the ever-growing fundamental roles of microRNAs in the brain, the possible molecular connections between the CB1 receptor and microRNAs are surprisingly unknown. Here, by using reporter gene constructs that express interaction sequences for microRNAs in human SH-SY5Y neuroblastoma cells, we show that CB1 receptor activation enhances the expression of several microRNAs, including let-7d. This was confirmed by measuring hsa-let-7d expression levels. Accordingly, knocking-down CB1 receptor in zebrafish reduced dre-let-7d levels, and knocking-out CB1 receptor in mice decreased mmu-let-7d levels in the cortex, striatum and hippocampus. Conversely, knocking-down let-7d increased CB1 receptor mRNA expression in zebrafish, SH-SY5Y cells and primary striatal neurons. Likewise, in primary striatal neurons chronically exposed to a cannabinoid or opioid agonist, a let-7d-inhibiting sequence facilitated not only cannabinoid or opioid signaling but also cannabinoid/opioid cross-signaling. Taken together, these findings provide the first evidence for a bidirectional link between the CB1 receptor and a microRNA, namely let-7d, and thus unveil a new player in the complex process of cannabinoid action. PMID:27179908

  3. 12. TRIPLE WINDOW, FIRST FLOOR, SOUTH SIDE. Typical for all ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. TRIPLE WINDOW, FIRST FLOOR, SOUTH SIDE. Typical for all triple windows on first and second floors. Note single swing jib door - John Joyner Smith House, 400 Wilmington Street, Beaufort, Beaufort County, SC

  4. LncRNAs as new biomarkers to differentiate triple negative breast cancer from non-triple negative breast cancer

    PubMed Central

    Huang, Lei; Li, Wenqu; Lv, Shanshan; Wu, Xiaowei; Zeng, Xin; Shen, Rong; Jia, Xuemei; Yin, Yongmei; Gu, Yun; Yuan, Hongyan; Xie, Hui; Fu, Ziyi

    2016-01-01

    Triple negative breast cancer (TNBC) is an aggressive type of breast cancer with high heterogeneity. To date, there is no efficient therapy for TNBC patients and the prognosis is poor. It is urgent to find new biomarkers for the diagnosis of TNBC or efficient therapy targets. As an area of focus in the post-genome period, long non-coding RNAs (lncRNAs) have been found to play critical roles in many cancers, including TNBC. However, there is little information on differentially expressed lncRNAs between TNBC and non-TNBC. We detected the expression levels of lncRNAs in TNBC and non-TNBC tissues separately. Then we analyzed the lncRNA expression signature of TNBC relative to non-TNBC, and found dysregulated lncRNAs participated in important biological processes though Gene Ontology and Pathway analysis. Finally, we validated these lncRNA expression levels in breast cancer tissues and cells, and then confirmed that 4 lncRNAs (RP11-434D9.1, LINC00052, BC016831, and IGKV) were correlated with TNBC occurrence through receiver operating characteristic curve analysis. This study offers helpful information to understand the initiation and development mechanisms of TNBC comprehensively and suggests potential biomarkers for diagnosis or therapy targets for clinical treatment. PMID:26910840

  5. 49 CFR 380.205 - LCV Triples.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... operate an LCV Triple, a driver-student shall, during the 6 months immediately preceding application for... preceding application, operated the applicable vehicle(s): (i) Group A truck-tractor/semi-trailer combination as described in § 383.91 of this subchapter; or (ii) Group A...

  6. 49 CFR 380.205 - LCV Triples.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... operate an LCV Triple, a driver-student shall, during the 6 months immediately preceding application for... preceding application, operated the applicable vehicle(s): (i) Group A truck-tractor/semi-trailer combination as described in § 383.91 of this subchapter; or (ii) Group A...

  7. Fixed Point Problems for Linear Transformations on Pythagorean Triples

    ERIC Educational Resources Information Center

    Zhan, M.-Q.; Tong, J.-C.; Braza, P.

    2006-01-01

    In this article, an attempt is made to find all linear transformations that map a standard Pythagorean triple (a Pythagorean triple [x y z][superscript T] with y being even) into a standard Pythagorean triple, which have [3 4 5][superscript T] as their fixed point. All such transformations form a monoid S* under matrix product. It is found that S*…

  8. Good publication practices in clinical pharmacology: transparency, evidence-based medicine and the 7-D assessment*

    PubMed Central

    Woodcock, Barry G.; Luger, Veronika

    2015-01-01

    Transparency and evidence-based medicine are cornerstones of good publication practices (GPP), and concern publishers, editors, research investigators, and reviewers alike. Methods for implementing these principles within the framework of GPP are described. The main aspects include obtaining a Manuscript Agreement Contract, a Statement on Transparency of Authorship and a Declaration of Conflicts of Interest from the authors. Assessing whether a manuscript meets the requirements of EBM is demonstrated using the “7-D assessment”. The main purpose of this tool is to established that the (1) right Design, (2) right Diagnosis, (3) right Drug molecule, (4) right Dosage, (5) right Data, (6) right Deductions, and (7) right Documentation have been implemented in order to meet the objectives of the investigation. If the findings from any one of these assessments is questionable, the compliance of the research with EBM principles will be weakened and the reviewers and editors will make recommendations to the publisher accordingly. The guidelines described will help to provide a fair and transparent process of scientific publication and foster the freedom of clinical pharmacological research. PMID:26329349

  9. Triple helical DNA in a duplex context and base pair opening

    PubMed Central

    Esguerra, Mauricio; Nilsson, Lennart; Villa, Alessandra

    2014-01-01

    It is fundamental to explore in atomic detail the behavior of DNA triple helices as a means to understand the role they might play in vivo and to better engineer their use in genetic technologies, such as antigene therapy. To this aim we have performed atomistic simulations of a purine-rich antiparallel triple helix stretch of 10 base triplets flanked by canonical Watson–Crick double helices. At the same time we have explored the thermodynamic behavior of a flipping Watson–Crick base pair in the context of the triple and double helix. The third strand can be accommodated in a B-like duplex conformation. Upon binding, the double helix changes shape, and becomes more rigid. The triple-helical region increases its major groove width mainly by oversliding in the negative direction. The resulting conformations are somewhere between the A and B conformations with base pairs remaining almost perpendicular to the helical axis. The neighboring duplex regions maintain a B DNA conformation. Base pair opening in the duplex regions is more probable than in the triplex and binding of the Hoogsteen strand does not influence base pair breathing in the neighboring duplex region. PMID:25228466

  10. Gauging triple stores with actual biological data

    PubMed Central

    2012-01-01

    Background Semantic Web technologies have been developed to overcome the limitations of the current Web and conventional data integration solutions. The Semantic Web is expected to link all the data present on the Internet instead of linking just documents. One of the foundations of the Semantic Web technologies is the knowledge representation language Resource Description Framework (RDF). Knowledge expressed in RDF is typically stored in so-called triple stores (also known as RDF stores), from which it can be retrieved with SPARQL, a language designed for querying RDF-based models. The Semantic Web technologies should allow federated queries over multiple triple stores. In this paper we compare the efficiency of a set of biologically relevant queries as applied to a number of different triple store implementations. Results Previously we developed a library of queries to guide the use of our knowledge base Cell Cycle Ontology implemented as a triple store. We have now compared the performance of these queries on five non-commercial triple stores: OpenLink Virtuoso (Open-Source Edition), Jena SDB, Jena TDB, SwiftOWLIM and 4Store. We examined three performance aspects: the data uploading time, the query execution time and the scalability. The queries we had chosen addressed diverse ontological or biological questions, and we found that individual store performance was quite query-specific. We identified three groups of queries displaying similar behaviour across the different stores: 1) relatively short response time queries, 2) moderate response time queries and 3) relatively long response time queries. SwiftOWLIM proved to be a winner in the first group, 4Store in the second one and Virtuoso in the third one. Conclusions Our analysis showed that some queries behaved idiosyncratically, in a triple store specific manner, mainly with SwiftOWLIM and 4Store. Virtuoso, as expected, displayed a very balanced performance - its load time and its response time for all the

  11. Do platinum salts fit all triple negative breast cancers?

    PubMed

    Gerratana, L; Fanotto, V; Pelizzari, G; Agostinetto, E; Puglisi, F

    2016-07-01

    Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options and poor prognosis once metastatic. Pre-clinical and clinical data suggest that TNBC could be more sensitive to platinum-based chemotherapy, especially among BRCA1/2-mutated patients. In recent years, several randomised trials have been conducted to evaluate platinum efficacy in both early-stage and advanced TNBC, with conflicting results especially for long-term outcomes. Experimental studies are now focusing on identifying biomarkers of response to help selecting patients who may benefit most from platinum-based therapies, including BRCA1/2 mutational status and genomic instability signatures (such as HRD-LOH or HRD-LST scores). A standard therapy for TNBC is still missing and platinum-based regimens represent an emerging therapeutic option for selected patients with a defect in the homologous recombination repair system. The identification of these patients through validated biomarker assays will be crucial to optimize the use of currently approved agents in TNBC. PMID:27343437

  12. Isotopically enhanced triple-quantum-dot qubit

    PubMed Central

    Eng, Kevin; Ladd, Thaddeus D.; Smith, Aaron; Borselli, Matthew G.; Kiselev, Andrey A.; Fong, Bryan H.; Holabird, Kevin S.; Hazard, Thomas M.; Huang, Biqin; Deelman, Peter W.; Milosavljevic, Ivan; Schmitz, Adele E.; Ross, Richard S.; Gyure, Mark F.; Hunter, Andrew T.

    2015-01-01

    Like modern microprocessors today, future processors of quantum information may be implemented using all-electrical control of silicon-based devices. A semiconductor spin qubit may be controlled without the use of magnetic fields by using three electrons in three tunnel-coupled quantum dots. Triple dots have previously been implemented in GaAs, but this material suffers from intrinsic nuclear magnetic noise. Reduction of this noise is possible by fabricating devices using isotopically purified silicon. We demonstrate universal coherent control of a triple-quantum-dot qubit implemented in an isotopically enhanced Si/SiGe heterostructure. Composite pulses are used to implement spin-echo type sequences, and differential charge sensing enables single-shot state readout. These experiments demonstrate sufficient control with sufficiently low noise to enable the long pulse sequences required for exchange-only two-qubit logic and randomized benchmarking. PMID:26601186

  13. Recombinant hepatitis B triple antigen vaccine: Hepacare.

    PubMed

    Zuckerman, Jane N; Zuckerman, Arie J

    2002-08-01

    Infection with hepatitis B virus is a public health problem throughout the world. Hepatitis B vaccines are now included in national immunization programmes of infants and/or adolescents in 129 countries. Current single antigen vaccines, that are plasma-derived or produced by recombinant DNA technology are highly effective, but between 5-10% or more of healthy immunocompetent subjects do not mount an antihepatitis B surface antibody protective response and others respond poorly (hyporesponders). The inclusion of pre-S1 and -S2 components of hepatitis B surface antigen in addition to the single antigen (triple antigen) in a novel vaccine, Hepacare, Medeva Pharma Plc, Speke, UK, overcomes nonresponsiveness and hyporesponsiveness in a significant number of individuals. The triple antigen is indicated for vaccination of nonresponders (and hyporesponders) to the current single antigen vaccines and for persons who require rapid protection against hepatitis B infection. PMID:12901552

  14. Isotopically enhanced triple-quantum-dot qubit.

    PubMed

    Eng, Kevin; Ladd, Thaddeus D; Smith, Aaron; Borselli, Matthew G; Kiselev, Andrey A; Fong, Bryan H; Holabird, Kevin S; Hazard, Thomas M; Huang, Biqin; Deelman, Peter W; Milosavljevic, Ivan; Schmitz, Adele E; Ross, Richard S; Gyure, Mark F; Hunter, Andrew T

    2015-05-01

    Like modern microprocessors today, future processors of quantum information may be implemented using all-electrical control of silicon-based devices. A semiconductor spin qubit may be controlled without the use of magnetic fields by using three electrons in three tunnel-coupled quantum dots. Triple dots have previously been implemented in GaAs, but this material suffers from intrinsic nuclear magnetic noise. Reduction of this noise is possible by fabricating devices using isotopically purified silicon. We demonstrate universal coherent control of a triple-quantum-dot qubit implemented in an isotopically enhanced Si/SiGe heterostructure. Composite pulses are used to implement spin-echo type sequences, and differential charge sensing enables single-shot state readout. These experiments demonstrate sufficient control with sufficiently low noise to enable the long pulse sequences required for exchange-only two-qubit logic and randomized benchmarking. PMID:26601186

  15. Triple orbital metastases from prostate cancer.

    PubMed

    Tun, Kagan; Bulut, Turgay

    2016-01-01

    Prostate carcinoma, when metastatic, typically involves bone and produces both osteoblastic and osteolytic changes. A 73-year-old man was admitted to our department because of unilateral progressive proptosis and visual blurriness for 3 months. The patient had a history of prostate adenocarcinoma diagnosis 5 years ago. We report a case of orbital involvement presented that intraorbital mass (including periocular structures), temporal bone and temporal muscle from prostate cancer. The mass was removed with total excision. Despite the frequency of bone metastasis in prostatic carcinoma, triple orbital metastases are extremely rare. The best of our knowledge, prostate adenocarcinoma and its triple (temporal bone, temporal muscle and intraorbital mass) orbital metastases have not been published previously. Metastatic orbital tumor secondary to prostate cancer should be considered in patients who have varying degrees of eye symptoms. PMID:27591068

  16. Triple quantum dots as charge rectifiers.

    PubMed

    Busl, M; Platero, G

    2012-04-18

    We theoretically analyze electronic spin transport through a triple quantum dot in series, attached to electrical contacts, where the drain contact is coupled to the central dot. We show that current rectification is observed in the device due to current blockade. The current blocking mechanism is originated by a destructive interference of the electronic wavefunction at the drain dot. There, the electrons are coherently trapped in a singlet two-electron dark state, which is a coherent superposition of the electronic wavefunction in the source dot and in the dot isolated from the contacts. Its formation gives rise to zero current and current rectification as the voltage is swept. We analyze this behavior analytically and numerically for both zero and finite magnetic dc fields. On top of that, we include phenomenologically a finite spin relaxation rate and calculate the current numerically. Our results show that triple dots in series can be designed to behave as quantum charge rectifiers. PMID:22442135

  17. Common base amplifier with 7 - dB gain at 176 GHz in InP mesa DHBT technology

    NASA Technical Reports Server (NTRS)

    Samoska, Lorene; Paidi, V.; Griffith, Z.; Dahlstrom, M.; Wei, Y.; Urteaga, M.; Rodell, M. J. W.; Fung, A.

    2004-01-01

    We report a single stage tunded amplifier that exhibits 7 dB small signal gain at 176 GHz. Common Base topology is chosen as it has the best maximum stable gain (MSG) in this frequency band when compared to common emitter and common collector topologies. The amplifiers are designed and fabricated in InP mesa double heterojunction bipolar transistor (DHBT) technology.

  18. 17 CFR 259.404 - Certificate to be filed pursuant to § 250.7(d) of this chapter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and on... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Certificate to be filed pursuant to § 250.7(d) of this chapter. 259.404 Section 259.404 Commodity and Securities...

  19. 17 CFR 270.7d-1 - Specification of conditions and arrangements for Canadian management investment companies...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.7d-1 Specification of conditions and... management investment company organized under the laws of Canada or any province thereof may obtain an order... company, or its directors, officers or employees, the Charter or By Laws shall state that the applicant...

  20. 17 CFR 270.7d-1 - Specification of conditions and arrangements for Canadian management investment companies...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.7d-1 Specification of conditions and... management investment company organized under the laws of Canada or any province thereof may obtain an order... company, or its directors, officers or employees, the Charter or By Laws shall state that the applicant...

  1. 17 CFR 270.7d-1 - Specification of conditions and arrangements for Canadian management investment companies...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.7d-1 Specification of conditions and... management investment company organized under the laws of Canada or any province thereof may obtain an order... company, or its directors, officers or employees, the Charter or By Laws shall state that the applicant...

  2. 17 CFR 270.7d-1 - Specification of conditions and arrangements for Canadian management investment companies...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.7d-1 Specification of conditions and... management investment company organized under the laws of Canada or any province thereof may obtain an order... company, or its directors, officers or employees, the Charter or By Laws shall state that the applicant...

  3. A 7-d toxicity test for marine pollutants using the Pacific mysid Mysidopsis intii. 1: Culture and protocol development

    SciTech Connect

    Langdon, C.J.; Vance, M.M.; Harmon, V.L.; Kreeger, K.E.; Kreeger, D.A.; Chapman, G.A.

    1996-10-01

    The purpose of this study was to develop a short term (7-d) toxicity test for marine pollutants that is practical to perform at sites remote from a source of test organisms. Laboratory culture methods were developed that allowed successful long-term rearing of populations of the mysid Mysidopsis intii, a species indigenous to the Pacific coast of the United States. Mysidopsis intii was found to have a short life cycle of 20 d at 20 C, making it useful for chronic toxicity tests. A 7-d toxicity test was developed by comparing the sensitivities of various life stages of M. intii to sodium dodecyl sulfate (SDS). The most sensitive end point was found to be growth (final body length) of juveniles during the first 7 d after release. The sensitivity of mysids to SDS decreased with increasing age. To allow for shipping newly released juveniles to remote sites, a 7-d test was evaluated starting with 2-d-old mysids. The median lethal concentration for M. intii exposed to SDS at ages from 2 to 9 d was 4.59 mg/L (95% confidence limits, 4.21--5.00), and the maximum acceptable SDS concentration was 4.99 mg/L for both survival and growth.

  4. Triple plasmon resonance of bimetal nanoshell

    SciTech Connect

    Shirzaditabar, Farzad; Saliminasab, Maryam; Arghavani Nia, Borhan

    2014-07-15

    In this paper, light absorption spectra properties of a bimetal multilayer nanoshell based on quasi-static approach are investigated. Comparing with silver-dielectric-silver and silver-dielectric-gold nanoshells, gold-dielectric-silver nanoshells have three intense and separated plasmon peaks which are more suitable for multiplex biosensing. Calculations show that relatively small thickness of outer silver shell and large dielectric constant of middle dielectric layer of gold-dielectric-silver nanoshell are suitable to obtain the triple plasmon resonance.

  5. Device Maintains Water At The Triple Point

    NASA Technical Reports Server (NTRS)

    West, J. W.; Burkett, C. G.

    1988-01-01

    Inexpensive device maintains water at 0.01 degree C for 10 weeks or longer. New device consists of four basic assemblies; small, commercial chest freezer containing insulated water tank; insulated copper cell holder; "ice switch" for cycling freezer compressor and externally-mounted air pump for circulation. Access hole in freezer lid allows triple point measurements without opening lid. Modified freezer used to calibrate standard platinum resistance thermomenters.

  6. On the Triple Origin of Blue Stragglers

    NASA Astrophysics Data System (ADS)

    Perets, Hagai B.; Fabrycky, Daniel C.

    2009-06-01

    Blue straggler stars (BSSs) are stars observed to be hotter and bluer than other stars with the same luminosity in their environment. As such they appear to be much younger than the rest of the stellar population. Two main channels have been suggested to produce such stars: (1) collisions between stars in clusters or (2) mass transfer between, or merger of, the components of primordial short-period binaries. Here we suggest a third scenario, in which the progenitors of BSSs are formed in primordial (or dynamically formed) hierarchical triple stars. In such configurations, the dynamical evolution of the triples through the Kozai mechanism and tidal friction can induce the formation of very close inner binaries. Angular momentum loss in a magnetized wind or stellar evolution could then lead to the merger of these binaries (or to mass transfer between them) and produce BSSs in binary (or triple) systems. We study this mechanism and its implications and show that it could naturally explain many of the characteristics of the BSS population in clusters, most notably the large binary fraction of long-period BSS binaries; their unique period-eccentricity distribution (with typical periods > 700 days); and the typical location of these BSSs in the color-magnitude diagram, far from the cluster turnoff point of their host clusters. We suggest that this scenario has a major (possibly dominant) role in the formation of BSSs in open clusters and give specific predictions for the BSSs population formed in this manner. We also note that triple systems may be the progenitors of the brightest planetary nebulae in old elliptical galaxies, which possibly evolved from BSSs.

  7. A Tulczyjew triple for classical fields

    NASA Astrophysics Data System (ADS)

    Grabowska, Katarzyna

    2012-04-01

    The geometrical structure known as the Tulczyjew triple has proved to be very useful in describing mechanical systems, even those with singular Lagrangians or subject to constraints. Starting from basic concepts of the variational calculus, we construct the Tulczyjew triple for first-order field theory. The important feature of our approach is that we do not postulate ad hoc the ingredients of the theory, but obtain them as unavoidable consequences of the variational calculus. This picture of field theory is covariant and complete, containing not only the Lagrangian formalism and Euler-Lagrange equations but also the phase space, the phase dynamics and the Hamiltonian formalism. Since the configuration space turns out to be an affine bundle, we have to use affine geometry, in particular the notion of the affine duality. In our formulation, the two maps α and β which constitute the Tulczyjew triple are morphisms of double structures of affine-vector bundles. We also discuss the Legendre transformation, i.e. the transition between the Lagrangian and the Hamiltonian formulation of the first-order field theory.

  8. Oral Tranexamic Acid with Fluocinolone-Based Triple Combination Cream Versus Fluocinolone-Based Triple Combination Cream Alone in Melasma: An Open Labeled Randomized Comparative Trial

    PubMed Central

    Padhi, Tanmay; Pradhan, Swetalina

    2015-01-01

    Background: Melasma is a common acquired cause of facial hyperpigmentation with no definitive therapy. Tranexamic acid, a plasmin inhibitor, has demonstrated depigmenting properties and combining this oral drug with other modalities of treatment has shown promising results. Objectives: To compare the efficacy of a combination of oral tranexamic acid and fluocinolone-based triple combination cream with that of fluocinolone-based triple combination cream alone in melasma among Indian patients. Materials and Methods: 40 patients of melasma of either sex attending to dermatology OPD were enrolled in this study. Participants were randomly divided into two groups with 20 patients in each group. Group A patients were asked to apply the cream only and Group B patients received oral tranexamic acid 250 mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01%, tretinoin 0.05%, and hydroquinone 2% once daily for 8 weeks. Response was evaluated using melasma area severity index (MASI) at baseline, 4 weeks, and 8 weeks. Results: 40 patients completed the study. The MASI scores at baseline, 4 weeks and 8 weeks in group A were 15.425 + 1.09, 11.075 + 9.167 and 6.995 + 6.056 respectively and in group B 18.243 + 1.05, 6.135 + 4.94 and 2.19 + 3.38. Intergroup comparison showed a faster reduction in pigmentation in Group B as compared to Group A and the results were statistically significant at 4 weeks (P value 0.014) and 8 weeks (P value 0.000). The efficacy was maintained throughout the 6-month follow-up period. Conclusion: Addition of oral tranexamic acid to fluocinolone-based triple combination cream results in a faster and sustained improvement in the treatment of melasma. PMID:26538719

  9. Triple dye plus rubbing alcohol versus triple dye alone for umbilical cord care.

    PubMed

    Suliman, Alawia K; Watts, Heidi; Beiler, Jessica; King, Tonya S; Khan, Sana; Carnuccio, Marybeth; Paul, Ian M

    2010-01-01

    Current practices for umbilical cord care vary across centers, but the evidence regarding these practices and their impact on cord separation, complications, and health care use are limited. The objective of this study was to compare the effect of triple dye alone (brilliant green, crystal violet, and proflavine hemisulfate) versus triple dye plus rubbing alcohol (isopropyl alcohol) twice daily on time to umbilical cord separation, complications, and health care use. For the 90 newborns who completed the study, there were no significant differences between treatment groups for time to cord separation, cord-related morbidities, or cord-related urgent care. Based on these study results, there does not appear to be significant benefit to the addition of twice daily applications of rubbing alcohol to neonatal umbilical cords following triple dye treatment after birth. PMID:20034947

  10. Polygonal triples and the double ruling of a hyperboloid

    NASA Astrophysics Data System (ADS)

    Yiu, Paul

    2012-09-01

    For a given positive integer k ≠ 4, let P k,n denote the n-th k-gonal number. We study k-gonal triples (a, b, c) satisfying A k-gonal triple corresponds to a rational point on the rectangular hyperboloid x 2 + y 2 = z 2 + 1. The simple observation that this is a doubly ruled surface leads to an easy, complete determination of k-gonal triples. The main result is expressed in terms of primitive Pythagorean triples. We also establish a correspondence between (2h + 1)-gonal triples and 4h-gonal triples.

  11. Triple-energy contrast enhanced digital mammography

    NASA Astrophysics Data System (ADS)

    Puong, Sylvie; Milioni de Carvalho, Pablo; Muller, Serge

    2010-04-01

    With the injection of iodine, Contrast Enhanced Digital Mammography (CEDM) provides functional information about breast tumour angiogenesis that can potentially help in cancer diagnosis. In order to generate iodine images in which the gray level is proportional to the iodine thickness, temporal and dual-energy approaches have already been considered. The dual-energy method offers the advantage of less patient motion artifacts and better comfort during the exam. However, this approach requires knowledge of the breast thickness at each pixel. Generally, as compression is applied, the breast thickness at each pixel is taken as the compression thickness. Nevertheless, in the breast border region, this assumption is not correct anymore and this causes inaccuracies in the iodine image. Triple-Energy CEDM could overcome these limitations by providing supplemental information in the form of a third image acquired with a different spectrum than the other two. This precludes the need of a priori knowledge of the breast thickness. Moreover, with Triple-Energy CEDM, breast thickness and glandularity maps could potentially be derived. In this study, we first focused on the method to recombine the three images in order to generate the iodine image, analyzing the performance of either quadratic, cubic or conic recombination functions. Then, we studied the optimal acquisition spectra in order to maximize the iodine SDNR in the recombined image for a given target total glandular dose. The concept of Triple-Energy CEDM was validated on simulated textured images and poly-energetic images acquired with a conventional X-ray mammography tube.

  12. Relative measurement of the photoionization cross section of the 7D5/2 state of cesium

    NASA Astrophysics Data System (ADS)

    Armstrong, D. J.; Westling, L. A.; Smith, S. J.

    1991-06-01

    We have carried out a relative measurement of the total photoionization cross section of the excited 7D5/2 state of cesium for photoelectron energies in the range 0.103-0.127 Ry above the ionization threshold. Separate measurements were made using two different combinations of laser sources to populate and photoionize the 7D5/2 state. The first measurement was made with a cw diode laser and two pulsed dye lasers, while the second was made with three pulsed dye lasers. The measured cross section was found to vary slowly within experimental uncertainty over this energy range but was otherwise featureless. This result disagrees with the cross section predicted by a Hartree-Slater calculation [J. Lahiri and S. T. Manson, Phys. Rev. A 33, 3151 (1986)], which displayed a deep minimum in this spectral region.

  13. Triple-negative breast cancer: bridging the gap from cancer genomics to predictive biomarkers

    PubMed Central

    Davis, S. Lindsey; Eckhardt, S. Gail; Tentler, John J.

    2014-01-01

    Triple-negative breast cancer (TNBC) represents a challenge clinically due to a lack of response to hormonal and HER2-targeted agents coupled with an aggressive disease course. As the biology of this breast cancer subtype is better understood, it is clear that TNBC is a heterogeneous disease and one targeted therapy is unlikely to be active in all patients. Biomarkers predictive of response to treatment are thus of great importance in TNBC. This review outlines studies evaluating biomarkers predictive of response to neoadjuvant chemotherapy and to targeted therapies in the advanced setting. The development of validated biomarkers in conjunction with novel targeted therapies represents an opportunity to improve patient outcomes in TNBC. PMID:24790649

  14. Triple X syndrome with rare phenotypic presentation.

    PubMed

    Jagadeesh, Sujatha; Jabeen, Gazala; Bhat, Lathaa; Vasikarla, Madhavi; Suresh, Arvind; Seshadri, Suresh; Lata, S

    2008-06-01

    Triple X syndrome is a rare numerical chromosomal anomaly, occurring as a result of non dysjunction in meiosis I. Most cases have neurodevelopmental defects and functional problems. We report two cases diagnosed in our centre. The first was a fetus with cleft lip and palate, 47, XXX was identified by Fetal Blood Sampling. The second was a child with multisystem anomaly including cleft lip and palate, whose karyotype also revealed 47, XXX. Though isolated cases of associated abnormalities have been reported there have not been consistent phenotypic changes reported with this condition. PMID:18759093

  15. Superexchange blockade in triple quantum dots

    NASA Astrophysics Data System (ADS)

    Sánchez, Rafael; Gallego-Marcos, Fernando; Platero, Gloria

    2014-04-01

    We propose the interaction of two electrons in a triple quantum dot as a minimal system to control long-range superexchange transitions. These are probed by transport spectroscopy. Narrow resonances appear indicating the transfer of charge from one side of the sample to the other with the central one being occupied only virtually. We predict that two different intermediate states establish the two arms of a one-dimensional interferometer. We find configurations where destructive interference of the two superexchange trajectories totally blocks the current through the system. We emphasize the role of spin correlations giving rise to lifetime-enhanced resonances.

  16. Determination of the Latent Heats and Triple Point of Perfluorocyclobutane

    ERIC Educational Resources Information Center

    Briggs, A. G.; Strachan, A. N.

    1977-01-01

    Proposes the use of Perfluorocyclobutane in physical chemistry courses to conduct experiments on latent heat, triple point temperatures and pressures, boiling points, and entropy of vaporization. (SL)

  17. Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein

    SciTech Connect

    Su, Hua-Poo; Golden, Joseph W.; Gittis, Apostolos G.; Hooper, Jay W.; Garboczi, David N.

    2007-11-25

    Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L1 protein, encoded by the L1R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D11, mAb-10F5) with potent neutralizing activity bind L1 in a conformation-specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L1 will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics.

  18. A possible family of B-like triple helix structures: comparison with the Arnott A-like triple helix.

    PubMed

    Ouali, M; Letellier, R; Adnet, F; Liquier, J; Sun, J S; Lavery, R; Taillandier, E

    1993-03-01

    Recent experimental studies of the structure of triple helices show that their conformation in solution differs from the A-like structure derived from diffraction data on triple helix fibers by Arnott and co-workers. Here we show by means of molecular modeling that a family of triple helix structures may exist with similar conformational energies, but with a variety of sugar puckers. The characteristics of these putative triple helices are analyzed for three different base sequences: (T.AxT)n, (C.GxC+)n, and alternating (C.GxC+/T.AxT)n. In the case of (C.GxC+)n triple helix, infrared and Raman spectra have been obtained and clearly reveal the existence of both N- and S-type sugars in solution. The molecular mechanics calculations allow us to propose a stereochemically reasonable model for this triple helix, in good agreement with the vibrational spectroscopy results. PMID:8448168

  19. Vectorized data acquisition and fast triple-correlation integrals for Fluorescence Triple Correlation Spectroscopy

    PubMed Central

    Ridgeway, William K; Millar, David P; Williamson, James R

    2013-01-01

    Fluorescence Correlation Spectroscopy (FCS) is widely used to quantitate reaction rates and concentrations of molecules in vitro and in vivo. We recently reported Fluorescence Triple Correlation Spectroscopy (F3CS), which correlates three signals together instead of two. F3CS can analyze the stoichiometries of complex mixtures and detect irreversible processes by identifying time-reversal asymmetries. Here we report the computational developments that were required for the realization of F3CS and present the results as the Triple Correlation Toolbox suite of programs. Triple Correlation Toolbox is a complete data analysis pipeline capable of acquiring, correlating and fitting large data sets. Each segment of the pipeline handles error estimates for accurate error-weighted global fitting. Data acquisition was accelerated with a combination of off-the-shelf counter-timer chips and vectorized operations on 128-bit registers. This allows desktop computers with inexpensive data acquisition cards to acquire hours of multiple-channel data with sub-microsecond time resolution. Off-line correlation integrals were implemented as a two delay time multiple-tau scheme that scales efficiently with multiple processors and provides an unprecedented view of linked dynamics. Global fitting routines are provided to fit FCS and F3CS data to models containing up to ten species. Triple Correlation Toolbox is a complete package that enables F3CS to be performed on existing microscopes. PMID:23525193

  20. A 7-d toxicity test for marine pollutants using the Pacific mysid Mysidopsis intii. 2: Protocol evaluation

    SciTech Connect

    Harmon, V.L.; Langdon, C.J.

    1996-10-01

    The sensitivity of the Pacific coast mysid Mysidopsis intii to pollutants was compared in 7-d toxicity tests with that of the Gulf coast mysid M. bahia and the Pacific coast mysid Holmesimysis costata. Survival and growth responses of M. intii to zinc (maximum acceptable toxicant concentration [MATC] survival and growth, 152 {micro}g/L) were as sensitive as survival of both M. bahia (MATC survival, 152 {micro}g/L) and H. costata (MATC survival, 152 {micro}g/L). In contrast, the 7-d test for M. intii was less sensitive (MATC growth and survival, 4.99 mg/L) than the test for H. costata (MATC survival, 1.99 mg/L) when sodium dodecyl sulfate (SDS) was used as the toxicant. Interlaboratory evaluation of the 7-d test for M. intii exposed to SDS indicated that the test was reliable. The mean test results for the group of participating laboratories were not significantly different from those of a group of three in-house tests, indicating that shipping and handling did not affect mysid sensitivity to SDS. Mysid growth was not as sensitive to SDS as survival in the interlaboratory tests. Although there were significant differences in median lethal concentration (LC50) values among participating laboratories, coefficients of variation of LC50 and MATC survival values among laboratories were 10.3 and 37%, respectively. These coefficients were comparable to those reported for interlaboratory tests with H. costata.

  1. New targets for triple-negative breast cancer.

    PubMed

    Herold, Christina I; Anders, Carey K

    2013-09-01

    Triple-negative breast cancer (TNBC) lacks the three most commonly targeted receptors in human breast cancer--the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)/neu--and it is associated with an aggressive natural history. More recently, TNBC has been further dissected into smaller, distinct subsets with unique molecular alterations and response to therapy. Large-scale genomic projects have yielded new knowledge about the molecular characteristics of TNBC, including similarities with high-grade serous ovarian cancers, suggesting a possible coordinated treatment algorithm for these malignancies. Moreover, translation of preclinical findings has led to clinical trials testing a plethora of targets and pathways in TNBC, which will be reviewed here; these include epidermal growth factor receptor (EGFR), angiogenesis, DNA repair capacity, epigenetic regulation, androgen receptor (AR) and folate receptor (FR) signaling, cell-cycle control, and cell survival. Given the complexity of TNBC biology and the lack of "traditional" therapeutic targets, the advancement of care for women with TNBC will require a true partnership between clinicians, translational investigators, and basic scientists. PMID:24282978

  2. The fate of chemoresistance in triple negative breast cancer (TNBC)

    PubMed Central

    O’Reilly, Elma A.; Gubbins, Luke; Sharma, Shiva; Tully, Riona; Guang, Matthew Ho Zhing; Weiner-Gorzel, Karolina; McCaffrey, John; Harrison, Michele; Furlong, Fiona; Kell, Malcolm; McCann, Amanda

    2015-01-01

    Background Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. Scope of Review How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. Major conclusions Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. General Significance Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy. PMID:26676166

  3. The triple threat of HIV-1 protease inhibitors.

    PubMed

    Potempa, Marc; Lee, Sook-Kyung; Wolfenden, Richard; Swanstrom, Ronald

    2015-01-01

    Newly released human immunodeficiency virus type 1 (HIV-1) particles obligatorily undergo a maturation process to become infectious. The HIV-1 protease (PR) initiates this step, catalyzing the cleavage of the Gag and Gag-Pro-Pol structural polyproteins. Proper organization of the mature virus core requires that cleavage of these polyprotein substrates proceeds in a highly regulated, specific series of events. The vital role the HIV-1 PR plays in the viral life cycle has made it an extremely attractive target for inhibition and has accordingly fostered the development of a number of highly potent substrate-analog inhibitors. Though the PR inhibitors (PIs) inhibit only the HIV-1 PR, their effects manifest at multiple different stages in the life cycle due to the critical importance of the PR in preparing the virus for these subsequent events. Effectively, PIs masquerade as entry inhibitors, reverse transcription inhibitors, and potentially even inhibitors of post-reverse transcription steps. In this chapter, we review the triple threat of PIs: the intermolecular cooperativity in the form of a cooperative dose-response for inhibition in which the apparent potency increases with increasing inhibition; the pleiotropic effects of HIV-1 PR inhibition on entry, reverse transcription, and post-reverse transcription steps; and their potency as transition state analogs that have the potential for further improvement that could lead to an inability of the virus to evolve resistance in the context of single drug therapy. PMID:25778681

  4. Mesothelin, a novel immunotherapy target for triple negative breast cancer

    PubMed Central

    Tchou, Julia; Wang, Liang-Chuan; Selven, Ben; Zhang, Hongtao; Conejo-Garcia, Jose; Borghaei, Hossein; Vondeheide, Robert H; Albelda, Steven M.; June, Carl H; Zhang, Paul J

    2016-01-01

    Mesothelin is a cell-surface glycoprotein present on mesothelial cells and elicits T-cell responses in a variety of cancers including pancreatic and ovarian cancer. Breast cancer is not known to express mesothelin. We postulated that mesothelin may be a unique tumor associated antigen in triple negative breast cancer (TNBC), a less common breast cancer subtype which may have been underrepresented in prior studies that characterized mesothelin expression. Therefore, we screened 99 primary breast cancer samples by immunohistochemistry analysis using formalin fixed paraffin embedded archival tumor tissues subtypes and confirmed that mesothelin was overexpressed in the majority of TNBC (67%) but only rarely in < 5% ER(+) or Her2-neu (+) breast cancer respectively. To determine whether mesothelin may be exploited as a novel immunotherapy target in breast cancer, an in vitro cell killing assay was performed to compare the ability of genetically modified T cells expressing a chimeric antibody receptor (CAR) specific for mesothelin (mesoCAR T-cells) or non-transduced T-cells to kill mesothelin-expressing primary breast cancer cells. A significantly higher anti-tumor cytotoxicity by mesoCAR T-cells was observed (31.7% vs. 8.7%, p<0.001). Our results suggest that mesothelin has promise as a novel immunotherapy target for TNBC for which effective targeted therapy is lacking to date. PMID:22418702

  5. Triple galaxies and a hidden mass problem

    NASA Technical Reports Server (NTRS)

    Karachentsev, I. D.; Karachentseva, V. E.; Lebedev, V. S.

    1990-01-01

    The authors consider a homogeneous sample of 84 triple systems of galaxies with components brighter than m = 15.7, located in the northern sky and satisfying an isolation criterion with respect to neighboring galaxies in projection. The distributions of basic dynamical parameters for triplets have median values as follows: radial velocity dispersion 133 km/s, mean harmonic radius 63 kpc, absolute magnitude of galaxies M sub B equals -20.38, crossing time tau = 0.04 H(sup minus 1). For different ways of estimation the median mass-to-luminosity ratio is (20 - 30). A comparison of the last value with the ones for single and binary galaxies shows the presence of a virial mass excess for triplets by a factor 4. The mass-to-luminosity ratio is practically uncorrelated with linear size of triplets or with morphological types of their components. We note that a significant part of the virial excess may be explained by the presence of nonisolated triple configurations in the sample, which are produced by debris of more populous groups of galaxies.

  6. Mergers and Obliquities in Stellar Triples

    NASA Astrophysics Data System (ADS)

    Naoz, Smadar; Fabrycky, Daniel C.

    2014-10-01

    Many close stellar binaries are accompanied by a faraway star. The "eccentric Kozai-Lidov" (EKL) mechanism can cause dramatic inclination and eccentricity fluctuations, resulting in tidal tightening of inner binaries of triple stars. We run a large set of Monte Carlo simulations, including the secular evolution of the orbits, general relativistic precession, and tides, and we determine the semimajor axis, eccentricity, inclination, and spin-orbit angle distributions of the final configurations. We find that the efficiency of forming tight binaries (lsim 16 days) when taking the EKL mechanism into account is ~21%, and about 4% of all simulated systems ended up in a merger event. These merger events can lead to the formation of blue stragglers. Furthermore, we find that the spin-orbit angle distribution of the inner binaries carries a signature of the initial setup of the system; thus, observations can be used to disentangle close binaries' birth configuration. The resulting inner and outer final orbits' period distributions and their estimated fraction suggest that secular dynamics may be a significant channel for the formation of close binaries in triples and even blue stragglers.

  7. Mergers and obliquities in stellar triples

    SciTech Connect

    Naoz, Smadar; Fabrycky, Daniel C.

    2014-10-01

    Many close stellar binaries are accompanied by a faraway star. The 'eccentric Kozai-Lidov' (EKL) mechanism can cause dramatic inclination and eccentricity fluctuations, resulting in tidal tightening of inner binaries of triple stars. We run a large set of Monte Carlo simulations, including the secular evolution of the orbits, general relativistic precession, and tides, and we determine the semimajor axis, eccentricity, inclination, and spin-orbit angle distributions of the final configurations. We find that the efficiency of forming tight binaries (≲ 16 days) when taking the EKL mechanism into account is ∼21%, and about 4% of all simulated systems ended up in a merger event. These merger events can lead to the formation of blue stragglers. Furthermore, we find that the spin-orbit angle distribution of the inner binaries carries a signature of the initial setup of the system; thus, observations can be used to disentangle close binaries' birth configuration. The resulting inner and outer final orbits' period distributions and their estimated fraction suggest that secular dynamics may be a significant channel for the formation of close binaries in triples and even blue stragglers.

  8. Triple Oxygen Isotopes: Fundamental Relationships and Applications

    NASA Astrophysics Data System (ADS)

    Bao, Huiming; Cao, Xiaobin; Hayles, Justin A.

    2016-06-01

    The element oxygen has three stable isotopes: 16O, 17O, and 18O. For a defined process, a change in 18O/16O scales with the corresponding change in 17O/16O, or the fractionation factors 18α and 17α have a relationship of θ = ln17α/ln18α, in which the triple oxygen isotope exponent θ is relatively fixed but does vary with reaction path, temperature, and species involved. When the small variation is of interest, the distinction of three concepts—θ, S (a slope through data points in δ17O–δ18O space), and C (an arbitrary referencing number for the degree of 17O deviation)—becomes important. Triple oxygen isotope variations can be measured by modern instruments and thus offer an additional line of information on the underlying reaction processes and conditions. Analytical methods and Earth science applications have recently been developed for air oxygen, carbon dioxide, water, silicates, oxides, sulfates, carbonates, and phosphates.

  9. Triple-activated blast furnace slag

    SciTech Connect

    Clarke, W.J.

    1995-12-31

    The current shortage of portland cement in the world will require the use of Ground Granulated Blast Furnace Slag (GGBFS) to fill demands in many industrialized countries. Therefore, an extensive series of triple-activated slag experiments have been undertaken to optimize an economical combination of mechanical properties for alkali-activated slags. Na{sub 2}OSiO{sub 2} (N Grade), Ca(OH){sub 2}, H{sub 2}O and Na{sub 2}CO{sub 3} have been added as activators in 5 to 10, 0 to 5 and 0 to 5 weight percentages of water and slag in a mix with a water:cement ratio of 1:1. Silica Fume and Sika 10 superplasticizer have been added as 1 and 10 weight percent of slag. Set times, initial hardening times and compressive strengths at percentages of the mix to identify more refined formulations. Finally, the resulting aggregate to develop a triple-activated slag formulation with the ultimate objective of contributing toward satisfying the world shortage of high performance concrete.

  10. IMMUNOHISTOCHEMICAL DIFFERENTIATION OF TRIPLE NEGATIVE BREAST CANCER.

    PubMed

    Lesar, Miroslav; Stanec, Mladen; Lesar, Nikola; Vrdoljak, Danko Velimir; Zore, Zvonimir; Banović, Marija; Brozović, Gordana

    2016-03-01

    Based on immunohistochemical staining for the basal markers cytokeratin 5/6 (CK 5/6), cytokeratin 14 (CK 14) and P-cadherin, triple negative tumors (TNT) are divided into two groups: 1) basal-like (BL) positive for one or all three markers; and 2) non basal-like (NBL) negative for all three markers. Even though the different origin of the cells of these two types of tumors implies different biological properties, they had been treated as one entity until recently. This paper analyzes TNT collected from 150 patients and distributed into two groups according to the results of immunohistochemical analysis, i.e. BL 116 (77.3%) and NBL 34 (22.67%). In this study, CK 5/6, CK 14 and P-cadherin were used as markers for identifying BL tumors. The immunohistochemical reaction was positive for CK 5/6 in 37%, for CK 14 in 50.86% and for P-cadherin in 68.34% of cases. The subclassification of triple negative breast cancer using the basal markers CK 5/6, CK 14 and P-cadherin has enabled identification of BL and NBL breast cancers in a proportion that is in line with the only accurate analysis of TNT gene expression. Using the mentioned combination of markers in daily practice is easy to perform and economically affordable. PMID:27333711

  11. Recovery and normalization of triple coincidences in PET

    SciTech Connect

    Lage, Eduardo Parot, Vicente; Dave, Shivang R.; Herraiz, Joaquin L.; Moore, Stephen C.; Sitek, Arkadiusz; Park, Mi-Ae; Udías, Jose M.; Vaquero, Juan J.

    2015-03-15

    Purpose: Triple coincidences in positron emission tomography (PET) are events in which three γ-rays are detected simultaneously. These events, though potentially useful for enhancing the sensitivity of PET scanners, are discarded or processed without special consideration in current systems, because there is not a clear criterion for assigning them to a unique line-of-response (LOR). Methods proposed for recovering such events usually rely on the use of highly specialized detection systems, hampering general adoption, and/or are based on Compton-scatter kinematics and, consequently, are limited in accuracy by the energy resolution of standard PET detectors. In this work, the authors propose a simple and general solution for recovering triple coincidences, which does not require specialized detectors or additional energy resolution requirements. Methods: To recover triple coincidences, the authors’ method distributes such events among their possible LORs using the relative proportions of double coincidences in these LORs. The authors show analytically that this assignment scheme represents the maximum-likelihood solution for the triple-coincidence distribution problem. The PET component of a preclinical PET/CT scanner was adapted to enable the acquisition and processing of triple coincidences. Since the efficiencies for detecting double and triple events were found to be different throughout the scanner field-of-view, a normalization procedure specific for triple coincidences was also developed. The effect of including triple coincidences using their method was compared against the cases of equally weighting the triples among their possible LORs and discarding all the triple events. The authors used as figures of merit for this comparison sensitivity, noise-equivalent count (NEC) rates and image quality calculated as described in the NEMA NU-4 protocol for the assessment of preclinical PET scanners. Results: The addition of triple-coincidence events with the

  12. Brown Dwarf Binaries from Disintegrating Triple Systems

    NASA Astrophysics Data System (ADS)

    Reipurth, Bo; Mikkola, Seppo

    2015-04-01

    Binaries in which both components are brown dwarfs (BDs) are being discovered at an increasing rate, and their properties may hold clues to their origin. We have carried out 200,000 N-body simulations of three identical stellar embryos with masses drawn from a Chabrier IMF and embedded in a molecular core. The bodies are initially non-hierarchical and undergo chaotic motions within the cloud core, while accreting using Bondi-Hoyle accretion. The coupling of dynamics and accretion often leads to one or two dominant bodies controlling the center of the cloud core, while banishing the other(s) to the lower-density outskirts, leading to stunted growth. Eventually each system transforms either to a bound hierarchical configuration or breaks apart into separate single and binary components. The orbital motion is followed for 100 Myr. In order to illustrate 200,000 end-states of such dynamical evolution with accretion, we introduce the “triple diagnostic diagram,” which plots two dimensionless numbers against each other, representing the binary mass ratio and the mass ratio of the third body to the total system mass. Numerous freefloating BD binaries are formed in these simulations, and statistical properties are derived. The separation distribution function is in good correspondence with observations, showing a steep rise at close separations, peaking around 13 AU and declining more gently, reaching zero at separations greater than 200 AU. Unresolved BD triple systems may appear as wider BD binaries. Mass ratios are strongly peaked toward unity, as observed, but this is partially due to the initial assumptions. Eccentricities gradually increase toward higher values, due to the lack of viscous interactions in the simulations, which would both shrink the orbits and decrease their eccentricities. Most newborn triple systems are unstable and while there are 9209 ejected BD binaries at 1 Myr, corresponding to about 4% of the 200,000 simulations, this number has grown to

  13. Triple Negative Breast Cancer: Role of Specific Chemotherapy Agents

    PubMed Central

    Isakoff, Steven J.

    2010-01-01

    Cytotoxic chemotherapy remains the mainstay of treatment for triple negative breast cancer (TNBC) despite the promise of new targeted and biologic agents. Many studies have shown significant benefit of chemotherapy in the neoadjuvant, adjuvant and metastatic treatment of TNBC. Neoadjuvant chemotherapy studies have consistently reported higher response rates in TNBC than non-TNBC, and pathologic complete response has been shown to predict improved long term outcomes for TNBC. Although the specific adjuvant regimens that may be most effective for TNBC are still being determined, third generation chemotherapy regimens utilizing dose dense or metronomic polychemotherapy are among the most effective tools presently available. The role of specific chemotherapy agents in the treatment of TNBC remains incompletely defined and warrants careful review to ensure the most effective therapy is delivered while minimizing unnecessary toxicity. Platinum agents have seen renewed interest in TNBC based on a growing body of preclinical and clinical data suggesting encouraging activity. Taxanes and anthracyclines are active in TNBC and remain important agents, but have not shown specific benefit over non-TNBC. Capecitabine has limited reported data in TNBC, but some reports suggest differential activity in TNBC compared to hormone receptor positive breast cancer. TNBC is itself a heterogeneous group in which subgroups such as BRCA1 mutation carriers may have particular sensitivity to platinum agents and relatively less sensitivity to taxanes. Therefore, the identification of additional molecular biomarkers to predict response to specific chemotherapy is required to further improve treatment strategies with the current menu of chemotherapy options and future combinations with targeted therapies. PMID:20164691

  14. Triple-responsive Expansile Nanogel for Tumor and Mitochondria Targeted Photosensitizer Delivery

    PubMed Central

    He, Huacheng; Cattran, Alexander W.; Nguyen, Tu; Nieminen, Anna-Liisa

    2014-01-01

    A pH, thermal, and redox potential triple-responsive expansile nanogel system (TRN), which swells at acidic pH, temperature higher than its transition temperature, and reducing environment, has been developed. TRN quickly expands from 108 nm to over 1200 nm (in diameter), achieving more than 1000-fold size enlargement (in volume), within 2 h in a reducing environment at body temperature. Sigma-2 receptor targeting-ligand functionalized TRN can effectively target head and neck tumor, and help Pc 4 targeting mitochondria inside cancer cells to achieve enhanced photodynamic therapy efficacy. PMID:25154666

  15. Regional Dimensions of the Triple Helix Model: Setting the Context

    ERIC Educational Resources Information Center

    Todeva, Emanuela; Danson, Mike

    2016-01-01

    This paper introduces the rationale for the special issue and its contributions, which bridge the literature on regional development and the Triple Helix model. The concept of the Triple Helix at the sub-national, and specifically regional, level is established and examined, with special regard to regional economic development founded on…

  16. A triple-color fluorescent probe for multiple nuclease assays.

    PubMed

    Xu, Qinfeng; Zhang, Yihong; Zhang, Chun-yang

    2015-06-01

    We develop a triple-color fluorescent probe which may function as a lab-on-a-DNA-molecule for simultaneous detection of multiple exonucleases/restriction endonucleases. This triple-color fluorescent probe can be further applied for the discrimination of seven exonucleases and four cell lines as well as the screening of various nuclease inhibitors. PMID:25940190

  17. Government and Governance of Regional Triple Helix Interactions

    ERIC Educational Resources Information Center

    Danson, Mike; Todeva, Emanuela

    2016-01-01

    This conceptual paper contributes to the discussion of the role of regional government and regional Triple Helix constellations driving economic development and growth within regional boundaries. The impact of regionalism and subsidiarity on regional Triple Helix constellations, and the questions of governmentality, governance and institutional…

  18. Spin waves in triple-q structures: Application to USb

    SciTech Connect

    Jensen, J.; Bak, P.

    1981-06-01

    The spin-wave spectrum in a system with triple-q magnetic structure is calculated. The spin waves differ distinctly from those in the corresponding single-q structure, but agree with the excitations observed by Lander and Stirling in uranium antimonide (USb). Their experiments thus directly verify that the spins in USb are ordered in the triple-q structure.

  19. Photoelectric UBV-photometry of triple-star components

    NASA Astrophysics Data System (ADS)

    Anosova, Zh. P.; Sudakov, S. V.

    Photoelectric UBV photometry has been obtained for components of 30 bright and nearby (V ⪉ 10m, r ⪉ 100 pc) triple stars for purposes of finding physically linked triple systems, their distances and the subsequent investigation of their dynamical evolution. For every component colour excesses EB-V and EU-B are determined and photometric parallaxes πph are calculated.

  20. 22. DETAIL OF TRIPLE WINDOW, SOUTHEAST ROOM, FIRST FLOOR. Typical ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. DETAIL OF TRIPLE WINDOW, SOUTHEAST ROOM, FIRST FLOOR. Typical for all triple windows on first and second floors. Single swing jib door under center sash opening out. Door thickness measures from flush with exterior siding to 3/4' inside bottom sash. See also Photo 12. SC-291-12. - John Joyner Smith House, 400 Wilmington Street, Beaufort, Beaufort County, SC

  1. Outcome Measures of Triple Board Graduates, 1991-2003

    ERIC Educational Resources Information Center

    Warren, Marla J.; Dunn, David W.; Rushton, Jerry

    2006-01-01

    Objective: To describe program outcomes for the Combined Training Program in Child and Adolescent Psychiatry, Pediatrics, and Psychiatry (Triple Board Program). Method: All Triple Board Program graduates to date (1991-2003) were asked to participate in a 37-item written survey from February to April 2004. Results: The response rate was 80.7%. Most…

  2. Rankin triple products and quantum chaos

    NASA Astrophysics Data System (ADS)

    Watson, Thomas Crawford

    2002-01-01

    In this dissertation we demonstrate the chaotic nature of some archetypical quantum dynamical systems, using machinery from analytic number theory. We consider the quantized geodesic flow on finite-volume hyperbolic surfaces G/H , with G⊂SL2R consisting of the norm-1 units of an Eichler order in an indefinite quaternion algebra B over Q . For G=SL2Z , we prove that high-energy bound eigen-states obey the Random Wave conjecture of Berry/Hejhal for third moments. In fact we show that the third moment of a wave's amplitude distribution decays like E-112+e . In the more general case of maximal orders, we reduce an optimal quantitative version of the Quantum Unique Ergodicity conjecture of Rudnick-Sarnak to the Lindelof Hypothesis for particular families of automorphic L-functions. Furthermore, our analysis shows that any lowering of the exponent in the Phragmen-Lindelof convexity bound implies QUE. In the moment problem as well, the maximum non-trivial exponents precisely agree when translated between physical and arithmetical formulations. We accomplish this translation by proving identities expressing triple-correlation integrals of eigenforms in terms of central values of the corresponding Rankin triple-product L-functions. Very general forms of such identities were proved by Harris-Kudla, and in using their method to prove our own classical identities, we have to solve two main problems. The first is to explicitly compute the adjoint of Shimizu's theta lift, which realizes the Jacquet-Langlands correspondence by transferring automorphic forms from GL2 to GO( B). We accomplish this for oldforms and newforms of square-free level, with (possibly imprimitive) neben-characters. As a byproduct of these calculations, we obtain explicit formulas for all relevant GL2 Whittaker functions. These play an important role in our second main problem: evaluation of Garrett/Rallis-Piatetsky-Shapiro local zeta integrals in terms of the standard functorial triple-product L

  3. Maximiscin Induces DNA Damage, Activates DNA Damage Response Pathways, and Has Selective Cytotoxic Activity against a Subtype of Triple-Negative Breast Cancer.

    PubMed

    Robles, Andrew J; Du, Lin; Cichewicz, Robert H; Mooberry, Susan L

    2016-07-22

    Triple-negative breast cancers are highly aggressive, and patients with these types of tumors have poor long-term survival. These breast cancers do not express estrogen or progesterone receptors and do not have gene amplification of human epidermal growth factor receptor 2; therefore, they do not respond to available targeted therapies. The lack of targeted therapies for triple-negative breast cancers stems from their heterogeneous nature and lack of a clear definition of driver defects. Studies have recently identified triple-negative breast cancer molecular subtypes based on gene expression profiling and representative cell lines, allowing for the identification of subtype-specific drug leads and molecular targets. We previously reported the identification of a new fungal metabolite named maximiscin (1) identified through a crowdsourcing program. New results show that 1 has selective cytotoxic efficacy against basal-like 1 MDA-MB-468 cells compared to cell lines modeling other triple-negative breast cancer molecular subtypes. This compound also exhibited antitumor efficacy in a xenograft mouse model. The mechanisms of action of 1 in MDA-MB-468 cells were investigated to identify potential molecular targets and affected pathways. Compound 1 caused accumulation of cells in the G1 phase of the cell cycle, suggesting induction of DNA damage. Indeed, treatment with 1 caused DNA double-strand breaks with concomitant activation of the DNA damage response pathways, indicated by phosphorylation of p53, Chk1, and Chk2. Collectively, these results suggest basal-like triple-negative breast cancer may be inherently sensitive to DNA-damaging agents relative to other triple-negative breast cancer subtypes. These results also demonstrate the potential of our citizen crowdsourcing program to identify new lead molecules for treating the subtypes of triple-negative breast cancer. PMID:27310425

  4. HD 207651: A composite spectrum triple system

    SciTech Connect

    Fekel, Francis C.

    2015-02-01

    From numerous radial velocities obtained at KPNO and Fairborn Observatory, we have determined the orbital elements of the composite spectrum triple system HD 207651. This system consists of a broad-lined A8 V star and an unseen M dwarf companion in a 1.470739 days orbit. Variations of the center-of-mass velocity of this short-period system and velocity variations of a narrow-lined F7: V star have an orbital period of 724.1 days or 1.98 yr and an eccentricity of 0.39. The revised Hipparcos parallax, corresponding to a distance of 255 pc, appears to be too small to yield consistent properties. Instead, we adopt a distance of 150 pc.

  5. On the uncontrollable damped triple inverted pendulum

    NASA Astrophysics Data System (ADS)

    Su, H.; Woodham, C. A.

    2003-02-01

    In this paper, the controllability of the damped triple inverted pendulum is investigated. The work is concerned with the form of the cancelling pole and zero which appear in the transfer functions of an uncontrollable system, and follows on from earlier work on the damped double inverted pendulum. The investigation considers first the cases where only one of the three arm frictions is non-zero, and then explores the cases when two of the three arm frictions are non-zero. Due to the complexity of this problem, and the difficulties with the symbolic manipulation software, exploratory numerical investigations have been carried out to facilitate the symbolic investigations, all of which are reported here.

  6. Triple grating polychromator for Thomson scattering.

    PubMed

    Greenwald, M; Smith, W I

    1977-03-01

    A high rejection, high transmission, triple grating polychromator with crossed dispersion has been designed and constructed for Thomson scattering plasma diagnostics. Identical gratings, collimating, and field lenses were used for all three stages. A mechanically convenient arrangement was made possible by using the field lenses to adjust the dispersion of the second stage to the required design value. The transmission in the passband for light polarized perpendicular to the rulings of the grating was measured at 33% for the instrument itself, and at 15% through the instrument and 1.8 m of attached fiber optics. With the 30-nm passband set 4-34-nm wavelengths away from the ruby laser line, the order of 10(-11) of 694-nm light incident in the input slit was present in each 3-nm wide output channel, giving a relative rejection factor of 10(-10). PMID:20168547

  7. Triple flames in microgravity flame spread

    NASA Technical Reports Server (NTRS)

    Wichman, Indrek S.

    1995-01-01

    The purpose of this project is to examine in detail the influence of the triple flame structure on the flame spread problem. It is with an eye to the practical implications that this fundamental research project must be carried out. The microgravity configuration is preferable because buoyancy-induced stratification and vorticity generation are suppressed. A more convincing case can be made for comparing our predictions, which are zero-g, and any projected experiments. Our research into the basic aspects will employ two models. In one, flows of fuel and oxidizer from the lower wall are not considered. In the other, a convective flow is allowed. The non-flow model allows us to develop combined analytical and numerical solution methods that may be used in the more complicated convective-flow model.

  8. Lie Triple Derivations of CSL Algebras

    NASA Astrophysics Data System (ADS)

    Yu, Weiyan; Zhang, Jianhua

    2013-06-01

    Let [InlineEquation not available: see fulltext.] be a commutative subspace lattice generated by finite many commuting independent nests on a complex separable Hilbert space [InlineEquation not available: see fulltext.] with [InlineEquation not available: see fulltext.], and [InlineEquation not available: see fulltext.] the associated CSL algebra. It is proved that every Lie triple derivation from [InlineEquation not available: see fulltext.] into any σ-weakly closed algebra [InlineEquation not available: see fulltext.] containing [InlineEquation not available: see fulltext.] is of the form X→ XT- TX+ h( X) I, where [InlineEquation not available: see fulltext.] and h is a linear mapping from [InlineEquation not available: see fulltext.] into ℂ such that h([[ A, B], C])=0 for all [InlineEquation not available: see fulltext.].

  9. Neutron triples counting data for uranium

    NASA Astrophysics Data System (ADS)

    Croft, Stephen; LaFleur, Adrienne M.; McElroy, Robert D.; Swinhoe, Martyn T.

    2015-06-01

    Correlated neutron counting using multiplicity shift register logic extracts the first three factorial moments from the detected neutron pulse train. The descriptive properties of the measurement item (mass, the ratio of (α,n) to spontaneous fission neutron production, and leakage self-multiplication) are related to the observed singles (S), doubles (D) and triples (T) rates, and this is the basis of the widely used multiplicity counting assay method. The factorial moments required to interpret and invert the measurement data in the framework of the point kinetics model may be calculated from the spontaneous fission prompt neutron multiplicity distribution P(ν). In the case of 238U very few measurements of P(ν) are available and the derived values, especially for the higher factorial moments, are not known with high accuracy. In this work, we report the measurement of the triples rate per gram of 238U based on the analysis of a set of measurements in which a collection of 10 cylinders of UO2F2, each containing about 230 g of compound, were measured individually and in groups. Special care was taken to understand and compensate the recorded multiplicity histograms for the effect of random cosmic-ray induced background neutrons, which, because they also come in bursts and mimic fissions but with a different and harder multiplicity distribution. We compare our fully corrected (deadtime, background, efficiency, multiplication) experimental results with first principles expectations based on evaluated nuclear data. Based on our results we suspect that the current evaluated nuclear data is biased, which points to a need to undertake new basic measurements of the 238U prompt neutron multiplicity distribution.

  10. Transcriptional gene silencing of dopamine D3 receptor caused by let-7d mimics in immortalized renal proximal tubule cells of rats.

    PubMed

    Zhang, Ye; Cheng, Caiyu; He, Duofen; Shi, Weibin; Fu, Chunjiang; Wang, Xukai; Zeng, Chunyu

    2016-04-15

    Transcriptional gene silencing (TGS) induced by synthetic exogenous short interfering RNAs (siRNAs) that are fully complementary to gene promoters has been demonstrated in mammalian cells. However, it remains unclear whether microRNAs (miRNAs), which are endogenous small regulatory RNAs, can also silence gene transcription. We investigated the regulation mechanism of let-7d on dopamine D3 receptor (DRD3) in immortalized renal proximal tubule (RPT) cells of rats, where let-7d has a predicted homologous target site within DRD3 promoter. We found that let-7d mimics repressed DRD3 expression at the transcription level in RPT cells. Let-7d induced DRD3 inhibition via DNA-methyltransferase 1 (DNMT1) and DNA-methyltransferase 3b (DNMT3b) dependent DNA methylation and the inhibition could be abolished by 5'-aza-2'-deoxycytidine (5-aza-dc), a DNA methylation inhibitor. Let-7d induced DRD3 repression was associated with the recruitment of Argonaute 2 (AGO2) protein. Histone 3 lysine 9 dimethylation (H3K9me2) was involved in the let-7d induced DRD3 TGS, indicating the chromatin-level silencing. In conclusion, our results demonstrated that let-7d may induce DRD3 repression in a transcriptional manner by means of DNMTs dependent DNA methylation and histone modification. It is suggested that miRNAs may act as a transcriptional gene regulator via the recognition of the homologous target site within the gene promoter. PMID:26802971

  11. [Period-tripling in Multiscale Physical and Biological Events].

    PubMed

    Bondar, A T; Fedorov, M V; Kolombet, V A

    2015-01-01

    A recent paper by S.J. Puetz et al. (Chaos, Solitons -& Fractals, v. 62-63, p. 55, 2014) described a fundamental period-tripled model. It involves periods of different astronomical (quasars, Sun), geophysical (geomagnetic, climatic, volcanic) and some biological processes. This work contains statistics for sixteen pairs of a period-tripled sequence. These periods range from -50 years to 1.5 billion years and no signs of the timescale limitations are found. We believe that the universal scope of the fundamental period-tripled model can be used for the development of new methodology of research data analysis: the main idea is that the spectrum of the periods of the studied event should be tested for the similarity with the spectrum of fundamental period-tripling pattern (because of the fundamental nature of the period-tripled model). Using this method, in this study we complement an already described period-tripled model with periods of human memory performance ranging from one minute to one month also adding seven relevant periods/frequencies of the period-tripled model in the range of human hearing. We make a conclusion that these characteristic frequencies may form the basis for music and singing phenomena. The new methodology is particularly appropriate for being applied in medicine and engineering. PMID:26841519

  12. The effects of complex chemistry on triple flames

    NASA Technical Reports Server (NTRS)

    Echekki, T.; Chen, J. H.

    1996-01-01

    The structure, ignition, and stabilization mechanisms for a methanol (CH3OH)-air triple flame are studied using Direct Numerical Simulations (DNS). The methanol (CH3OH)-air triple flame is found to burn with an asymmetric shape due to the different chemical and transport processes characterizing the mixture. The excess fuel, methanol (CH3OH), on the rich premixed flame branch is replaced by more stable fuels CO and H2, which burn at the diffusion flame. On the lean premixed flame side, a higher concentration of O2 leaks through to the diffusion flame. The general structure of the triple point features the contribution of both differential diffusion of radicals and heat. A mixture fraction-temperature phase plane description of the triple flame structure is proposed to highlight some interesting features in partially premixed combustion. The effects of differential diffusion at the triple point add to the contribution of hydrodynamic effects in the stabilization of the triple flame. Differential diffusion effects are measured using two methods: a direct computation using diffusion velocities and an indirect computation based on the difference between the normalized mixture fractions of C and H. The mixture fraction approach does not clearly identify the effects of differential diffusion, in particular at the curved triple point, because of ambiguities in the contribution of carbon and hydrogen atoms' carrying species.

  13. A Novel Triple Medicine Combination Injection for the Resolution of Keloids and Hypertrophic Scars

    PubMed Central

    Gold, Michael H.

    2014-01-01

    Keloids and hypertrophic scars remain one of the more difficult treatment concerns for clinicians. A variety of therapies have been used in the past with moderate success. On occasion, combination therapy has been used to treat these lesion, in an attempt to lessen the symptoms of pain and pruritus that often accompanies keloids and hypertrophic scars, as well as treating the actual lesions themselves. A novel triple combination injection process is introduced here in an attempt to further reduce the signs and symptoms of these lesions. The combination includes 5-fluoruracil, triamcinolone acetonide, and hyaluronidase. All three work in concert to treat keloids and hypertrophic scars, and this is the first work at looking at these medicines given together, at the same time, in a series of recalcitrant keloids and hypertrophic scars. The positive results warrant further investigation and hope for those with keloids and hypertrophic scars. PMID:25489380

  14. Effects of Gravity on Triple Flame Propagation and Stability

    NASA Technical Reports Server (NTRS)

    Chen, J.-Y.; Echekki, Tarek; Hugde, Uday

    2001-01-01

    Numerical simulations of 2-D triple flames under gravity force have been implemented to identify the effects of gravity on triple flame structure and propagation properties and to understand the mechanisms of instabilities resulting from both heat release and buoyancy effects. A wide range of gravity conditions, heat release and mixing widths for a scalar mixing layer are computed for downward-propagating (in the same direction with the gravity vector) and upward-propagating (in the opposite direction of the gravity vector) triple flames.

  15. Triple helix structures: sequence dependence, flexibility and mismatch effects.

    PubMed

    Sun, J S; Mergny, J L; Lavery, R; Montenay-Garestier, T; Hélène, C

    1991-12-01

    By means of molecular modelling, electrostatic interactions are shown to play an important role in the sequence-dependent structure of triple helices formed by a homopyrimidine oligonucleotide bound to a homopurine. homopyrimidine sequence on DNA. This is caused by the presence of positive charges due to the protonation of cytosines in the Hoogsteen-bonded strand, required in order to form C.GxC+ triplets. Energetic and conformational characteristics of triple helices with different sequences are analyzed and discussed. The effects of duplex mismatches on the triple helix stability are investigated via thermal dissociation using UV absorption. PMID:1815635

  16. Spectroscopic properties of the triple bond carotenoid alloxanthin

    NASA Astrophysics Data System (ADS)

    West, Robert; Keşan, Gürkan; Trsková, Eliška; Sobotka, Roman; Kaňa, Radek; Fuciman, Marcel; Polívka, Tomáš

    2016-06-01

    Alloxanthin, which has two triple bonds within its backbone, was studied by steady-state and femtosecond transient absorption spectroscopies. Alloxanthin demonstrates an S2 energy comparable to its non-triple bond homolog, zeaxanthin, while the S1 lifetime of 19 ps is markedly longer than that of zeaxanthin (9 ps). Along with corroborating quantum chemistry calculations, the results show that the long-lived S1 state of alloxanthin, which typically corresponds to the dynamic of a shorter carotenoid backbone, implies the triple bond isolates the conjugation of the backbone, increasing the S1 state energy and diminishing the S1-S2 energy gap.

  17. Repair and recombination induced by triple helix DNA.

    PubMed

    Chin, Joanna Y; Schleifman, Erica B; Glazer, Peter M

    2007-01-01

    Triple-helix DNA structures can form endogenously at mirror repeat polypurine/polypyrimidine sequences or by introduction of triplex-forming oligonucleotides (TFOs). Recent evidence suggests that triple helices are sources of genetic instability, and are subject to increased rates of mutagenesis and recruitment of repair factors. Indeed, observations using TFOs suggest that triple helices provoke a variety of biological processes which can be harnessed to modulate gene expression and induce heritable changes in targeted genes. This review surveys the biological applications of TFOs, with particular attention to their recombinogenic and mutagenic potential, and summarizes available evidence for the mechanism of triplex and triplex-associated repair. PMID:17485375

  18. Complicated triple gallbladder: clinical presentation and surgical approach.

    PubMed

    Copeland-Halperin, Libby R; Kapoor, Kunal; Piper, James B

    2016-01-01

    We report a patient with previous biliary symptoms and endoscopic interventions who presented with clinical features suggestive of choledocholithiasis. Open surgical exploration disclosed three gallbladders with copious stones and varying degrees of acute and chronic inflammation. Literature review revealed only 16 previously reported cases. We review the aetiology of triple gallbladder as being due to failure of rudimentary bile ducts to regress during embryological development, as well as the classification scheme of triple gallbladder based on size, location and number. We also discuss the clinical evaluation and appropriate surgical management of this entity, as triple gallbladders can be associated with cholecystitis or carcinoma. PMID:27435847

  19. Zeroing the Baseball Indicator and the Chirality of Triples

    NASA Astrophysics Data System (ADS)

    Simons, Christopher S.; Wright, Marcus

    2004-03-01

    Starting with a common baseball umpire indicator, we consider the zeroing number for two-wheel indicators with states (a,b) and three-wheel indicators with states (a,b,c). Elementary number theory yields formulae for the zeroing number. The solution in the three-wheel case involves a curiously nontrivial minimization problem whose solution determines the chirality of the ordered triple (a,b,c) of pairwise relatively prime numbers. We prove that chirality is in fact an invariant of the unordered triple {a,b,c }. We also show that the chirality of Fibonacci triples alternates between 1 and 2.

  20. Comparison of Ciprofloxacin-Based Triple Therapy with Conventional Triple Regimen for Helicobacter pylori Eradication in Children.

    PubMed

    Farahmand, Fatemeh; Mohammadi, Tayebeh; Najafi, Mehri; Fallahi, Gholamhosein; Khodadad, Ahmad; Motamed, Farzaneh; Mahdi Marashi, Sayed; Shoaran, Maryam; Nabavizadeh Rafsanjani, Raheleh

    2016-06-01

    Helicobacter pylori infection is a prevalent disease among Iranian children. The purpose of this study was to compare the effect of ciprofloxacin and furazolidone on eradicating helicobacter pylori in Iranian children in combination with amoxicillin and omeprazole. In this cohort study, helicobacter pylori infection was confirmed by gastroscopy, rapid urease test or pathologic assessments. A total of 66 children were randomly enrolled; based on the random number table, and were divided into two groups; first, a combination regimen consisting of ciprofloxacin, amoxicillin, and omeprazole; second, a three-medication regimen consisting of amoxicillin, furazolidone, and omeprazole. The effect of both medical regimens on the successful eradication of helicobacter pylori infection was assessed and compared. Chi-square test was used for evaluating the association between quantitative variables. All comparisons were made at the significance of P<0.05. Endoscopic tests prior to initiating treatments showed that 66.7% of the patients had a degree of nodularity while peptic ulcer was only observed in one patient. One month after the end of the treatments, eradication of the helicobacter pylori infection was reported 87.9% (29/33) in the first group (CAO) and 60.6% (20.33) in the second group (FAO) (P=0.011). It appears that a major advantage of our proposed regimen over others is a lack of wide use of fluoroquinolones for treating children's diseases. Given FDA's recommendation about the possibility of prescribing ciprofloxacin for infected patients with multidrug resistance, we can use the regimen proposed in this study in patients with resistance to standard treatments. PMID:27306347

  1. DNA repair genes implicated in triple negative familial non-BRCA1/2 breast cancer predisposition

    PubMed Central

    Ollier, Marie; Radosevic-Robin, Nina; Kwiatkowski, Fabrice; Ponelle, Flora; Viala, Sandrine; Privat, Maud; Uhrhammer, Nancy; Bernard-Gallon, Dominique; Penault-Llorca, Frédérique; Bignon, Yves-Jean; Bidet, Yannick

    2015-01-01

    Among breast cancers, 10 to 15% of cases would be due to hereditary risk. In these familial cases, mutations in BRCA1 and BRCA2 are found in only 15% to 20%, meaning that new susceptibility genes remain to be found. Triple-negative breast cancers represent 15% of all breast cancers, and are generally aggressive tumours without targeted therapies available. Our hypothesis is that some patients with triple negative breast cancer could share a genetic susceptibility different from other types of breast cancers. We screened 36 candidate genes, using pyrosequencing, in all the 50 triple negative breast cancer patients with familial history of cancer but no BRCA1 or BRCA2 mutation of a population of 3000 families who had consulted for a familial breast cancer between 2005 and 2013. Any mutations were also sequenced in available relatives of cases. Protein expression and loss of heterozygosity were explored in tumours. Seven deleterious mutations in 6 different genes (RAD51D, MRE11A, CHEK2, MLH1, MSH6, PALB2) were observed in one patient each, except the RAD51D mutation found in two cases. Loss of heterozygosity in the tumour was found for 2 of the 7 mutations. Protein expression was absent in tumour tissue for 5 mutations. Taking into consideration a specific subtype of tumour has revealed susceptibility genes, most of them in the homologous recombination DNA repair pathway. This may provide new possibilities for targeted therapies, along with better screening and care of patients. PMID:26328243

  2. Triple parton scattering in collinear approximation of perturbative QCD

    NASA Astrophysics Data System (ADS)

    Snigirev, A. M.

    2016-08-01

    Revised formulas for the inclusive cross section of a triple parton scattering process in a hadron collision are suggested based on the modified collinear three-parton distributions. The possible phenomenological issues are discussed.

  3. 42. DETAIL VIEW OF TRIPLED, HEAVY TIMBER TRUSSES IN FOUNDRY. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. DETAIL VIEW OF TRIPLED, HEAVY TIMBER TRUSSES IN FOUNDRY. - Baltimore & Ohio Railroad, Mount Clare Shops, South side of Pratt Street between Carey & Poppleton Streets, Baltimore, Independent City, MD

  4. 41. DETAIL VIEW OF TRIPLED, HEAVY TIMBER TRUSSES IN FOUNDRY. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. DETAIL VIEW OF TRIPLED, HEAVY TIMBER TRUSSES IN FOUNDRY. - Baltimore & Ohio Railroad, Mount Clare Shops, South side of Pratt Street between Carey & Poppleton Streets, Baltimore, Independent City, MD

  5. 43. DETAIL VIEW OF TRIPLED, HEAVY TIMBER TRUSSES IN FOUNDRY. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    43. DETAIL VIEW OF TRIPLED, HEAVY TIMBER TRUSSES IN FOUNDRY. - Baltimore & Ohio Railroad, Mount Clare Shops, South side of Pratt Street between Carey & Poppleton Streets, Baltimore, Independent City, MD

  6. Northwest corner, showing arcade at ground level, and triple leaded ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Northwest corner, showing arcade at ground level, and triple leaded glass windows of bender room high on north elevation. - Stanford University Library, Stanford University, Palo Alto, Santa Clara County, CA

  7. Detail of triple casement windows with operable transoms in north ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of triple casement windows with operable transoms in north wall of garage, facing north. - Marine Barracks, Panama Canal, Officers' Quarters, 800' West of Bruja Road, Balboa, Former Panama Canal Zone, CZ

  8. 4. DETAIL VIEW OF TRIPLE TONGUE AND GROOVE CRIBBING USED ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. DETAIL VIEW OF TRIPLE TONGUE AND GROOVE CRIBBING USED IN DAM CONSTRUCTION, NORTH EAST OF EAST DAM, LOOKING NORTH - Three Bears Lake & Dams, East Dam, North of Marias Pass, East Glacier Park, Glacier County, MT

  9. Elevation of north facades of #156158 (triple wards) National ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Elevation of north facades of #156-158 (triple wards) - National Home for Disabled Volunteer Soldiers, Pacific Branch, Mental Health Buildings, 11301 Wilshire Boulevard, West Los Angeles, Los Angeles County, CA

  10. 42. DETAIL OF TRIPLE WINDOW ELEMENT WITH DECORATIVE BRICK SURROUND, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    42. DETAIL OF TRIPLE WINDOW ELEMENT WITH DECORATIVE BRICK SURROUND, ON EAST SIDE OF 1931 SECTION, TAKEN FROM THE EAST. - James Russell Lowell Elementary School, 4501 Crittenden Drive, Louisville, Jefferson County, KY

  11. Triple simultaneous primary invasive gynecological malignancies: a case report.

    PubMed

    Takatori, Eriko; Shoji, Tadahiro; Miura, Yuki; Takeuchi, Satoshi; Uesugi, Noriyuki; Sugiyama, Toru

    2014-02-01

    Double gynecologic cancer (primary cancers in two organs) is relatively rare. However, triple gynecologic cancer (primary cancers in three organs) is extremely rare. We experienced a case of triple cancer, with primary cervical, endometrial and ovarian cancers, each showing different histopathological features. A 50-year-old woman with a preoperative diagnosis of cervical cancer stage Ib1 with a pathological diagnosis of mucinous adenocarcinoma underwent radical hysterectomy. The pathological diagnoses of the extracted masses were endometrioid adenocarcinoma in the uterine corpus and serous adenocarcinoma in the left ovary. Consequently, triple cancer was diagnosed. After the operation, six cycles of a paclitaxel/carboplatin regimen were administered, and no relapse of the cancers has been observed to date. To our knowledge, this is only the second case report in the international literature of concurrent gynecologic triple cancers of epithelial origin; that is, invasive cervical, endometrial and ovarian cancers, each with different histopathological features. PMID:24147606

  12. Radiological evidence for the triple bundle anterior cruciate ligament.

    PubMed

    MacKay, James W; Whitehead, Harry; Toms, Andoni P

    2014-10-01

    The anterior cruciate ligament (ACL) has traditionally been described as having two bundles--one anteromedial and one posterolateral. This has been challenged by studies proposing the existence of a third, intermediate, bundle with distinct functional significance, an arrangement that has been described in a number of domesticated animal species. No radiological evidence for the triple bundle ACL has previously been described. A prevalence study was carried out on 73 consecutive human knee magnetic resonance (MR) studies to determine the number of visible bundles, excluding individuals with a history of ACL injury or mucoid degeneration. A triple bundle ACL was demonstrated in 15 out of 73 human knees (20.5%, 95% confidence interval 12.9-31.2%). This is the first radiological description of the human triple bundle ACL. There was MR imaging evidence of a triple bundle ACL in approximately one fifth of human knees in this study. PMID:24890455

  13. Morita equivalence and spectral triples on noncommutative orbifolds

    NASA Astrophysics Data System (ADS)

    Harju, Antti J.

    2016-08-01

    Let G be a finite group. Noncommutative geometry of unital G-algebras is studied. A geometric structure is determined by a spectral triple on the crossed product algebra associated with the group action. This structure is to be viewed as a representative of a noncommutative orbifold. Based on a study of classical orbifold groupoids, a Morita equivalence for the crossed product spectral triples is developed. Noncommutative orbifolds are Morita equivalence classes of the crossed product spectral triples. As a special case of this Morita theory one can study freeness of the G-action on the noncommutative level. In the case of a free action, the crossed product formalism reduced to the usual spectral triple formalism on the algebra of G-invariant functions.

  14. A Study of Neoadjuvant Paclitaxel in Combination With Bavituximab in Early- Stage Triple- Negative Breast Cancer

    ClinicalTrials.gov

    2016-02-12

    Breast Cancer; Triple Negative Breast Neoplasms; Triple-Negative Breast Neoplasm; Triple-Negative Breast Cancer; Triple Negative Breast Cancer; ER-Negative PR-Negative HER2-Negative Breast Neoplasms; ER-Negative PR-Negative HER2-Negative Breast Cancer

  15. MicroRNA let-7d regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis

    PubMed Central

    Zhao, Chunnian; Sun, GuoQiang; Ye, Peng; Li, Shengxiu; Shi, Yanhong

    2013-01-01

    MicroRNAs have important functions in the nervous system through post-transcriptional regulation of neurogenesis genes. Here we show that microRNA let-7d, which has been implicated in cocaine addiction and other neurological disorders, targets the neural stem cell regulator TLX. Overexpression of let-7d in vivo reduced neural stem cell proliferation and promoted premature neuronal differentiation and migration, a phenotype similar to those induced by TLX knockdown or overexpression of its negatively-regulated target, microRNA-9. We found a let-7d binding sequence in the tlx 3′ UTR and demonstrated that let-7d reduced TLX expression levels in neural stem cells, which in turn, up-regulated miR-9 expression. Moreover, co-expression of let-7d and TLX lacking its 3′ UTR in vivo restored neural stem cell proliferation and reversed the premature neuronal differentiation and migration. Therefore, manipulating let-7d and its downstream targets could be a novel strategy to unravel neurogenic signaling pathways and identify potential interventions for relevant neurological disorders. PMID:23435502

  16. Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group

    PubMed Central

    Matloub, Yousif; Lindemulder, Susan; Gaynon, Paul S.; Sather, Harland; La, Mei; Broxson, Emmett; Yanofsky, Rochelle; Hutchinson, Raymond; Heerema, Nyla A.; Nachman, James; Blake, Marilyn; Wells, Linda M.; Sorrell, April D.; Masterson, Margaret; Kelleher, John F.; Stork, Linda C.

    2006-01-01

    The Children's Cancer Group (CCG) 1952 clinical trial for children with standard-risk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT) methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% ± 1.0% for ITT and 5.9% ± 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% ± 1.9% and 82.5% ± 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% ± 1.5% versus 94.4% ± 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome. PMID:16609069

  17. Inventory of veterinary syndromic surveillance initiatives in Europe (Triple-S project): current situation and perspectives.

    PubMed

    Dupuy, Céline; Bronner, Anne; Watson, Eamon; Wuyckhuise-Sjouke, Linda; Reist, Martin; Fouillet, Anne; Calavas, Didier; Hendrikx, Pascal; Perrin, Jean-Baptiste

    2013-09-01

    Within the current context that favours the emergence of new diseases, syndromic surveillance (SyS) appears increasingly more relevant tool for the early detection of unexpected health events. The Triple-S project (Syndromic Surveillance Systems in Europe), co-financed by the European Commission, was launched in September 2010 for a three year period to promote both human and animal health SyS in European countries. Objectives of the project included performing an inventory of current and planned European animal health SyS systems and promoting knowledge transfer between SyS experts. This study presents and discusses the results of the Triple-S inventory of European veterinary SyS initiatives. European SyS systems were identified through an active process based on a questionnaire sent to animal health experts involved in SyS in Europe. Results were analyzed through a descriptive analysis and a multiple factor analysis (MFA) in order to establish a typology of the European SyS initiatives. Twenty seven European SyS systems were identified from twelve countries, at different levels of development, from project phase to active systems. Results of this inventory showed a real interest of European countries for SyS but also highlighted the novelty of this field. This survey highlighted the diversity of SyS systems in Europe in terms of objectives, population targeted, data providers, indicators monitored. For most SyS initiatives, statistical analysis of surveillance results was identified as a limitation in using the data. MFA results distinguished two types of systems. The first one belonged to the private sector, focused on companion animals and had reached a higher degree of achievement. The second one was based on mandatory collected data, targeted livestock species and is still in an early project phase. The exchange of knowledge between human and animal health sectors was considered useful to enhance SyS. In the same way that SyS is complementary to traditional

  18. Neutral triple and quartic gauge couplings at LEP

    NASA Astrophysics Data System (ADS)

    Ofierzynski, R.

    2002-06-01

    The possible existence of neutral triple ZZZ, ZZγ and Zγγ and quartic ZZγγ gauge boson couplings is investigated. Based on data collected at LEP2 at centre-of-mass energies up to 208 GeV no evidence has been found for such couplings. Preliminary limits for neutral triple gauge couplings as obtained from the combination of the LEP experiments are presented.

  19. Double and triple photoionization of Li and Be

    SciTech Connect

    Colgan, J.; Pindzola, M.S.; Robicheaux, F.

    2005-08-15

    We present calculations for the double photoionization (with excitation) and the triple photoionization of Li and Be. We extend and more fully discuss the previous calculations made for Li by Colgan et al. [Phys. Rev. Lett. 93, 053201 (2004)] and present calculations for Be. The Be triple photoionization cross sections are compared with previous double shake-off model calculations of Kheifets and Bray [J. Phys. B 36, L211 (2003)], and our calculations are found to be significantly lower.

  20. Double and triple photoionization of Li and Be

    NASA Astrophysics Data System (ADS)

    Colgan, J.; Pindzola, M. S.; Robicheaux, F.

    2005-08-01

    We present calculations for the double photoionization (with excitation) and the triple photoionization of Li and Be. We extend and more fully discuss the previous calculations made for Li by Colgan et al. [Phys. Rev. Lett. 93, 053201 (2004)] and present calculations for Be. The Be triple photoionization cross sections are compared with previous double shake-off model calculations of Kheifets and Bray [J. Phys. B 36, L211 (2003)], and our calculations are found to be significantly lower.

  1. Polygonal Triples and the Double Ruling of a Hyperboloid

    ERIC Educational Resources Information Center

    Yiu, Paul

    2012-01-01

    For a given positive integer k [not equal] 4, let "P[subscript k,n]" denote the "n"-th "k"-gonal number. We study "k"-gonal triples ("a", "b", "c") satisfying P[subscript k,a] + P[subscript k,b] = P[subscript k,c]. A "k"-gonal triple corresponds to a rational point on the rectangular hyperboloid x[squared] + y[squared] = z[squared] + 1. The simple…

  2. Boundedness of completely additive measures with application to 2-local triple derivations

    NASA Astrophysics Data System (ADS)

    Hamhalter, Jan; Kudaybergenov, Karimbergen; Peralta, Antonio M.; Russo, Bernard

    2016-02-01

    We prove a Jordan version of Dorofeev's boundedness theorem for completely additive measures and use it to show that every (not necessarily linear nor continuous) 2-local triple derivation on a continuous JBW∗-triple is a triple derivation. 2-local triple derivations are well understood on von Neumann algebras. JBW*-triples, which are properly defined in Section I, are intimately related to infinite dimensional holomorphy and include von Neumann algebras as special cases. In particular, continuous JBW∗-triples can be realized as subspaces of continuous von Neumann algebras which are stable for the triple product xy∗z + zy∗x and closed in the weak operator topology.

  3. A directional nucleation-zipping mechanism for triple helix formation

    PubMed Central

    Alberti, Patrizia; Arimondo, Paola B.; Mergny, Jean-Louis; Garestier, Thérèse; Hélène, Claude; Sun, Jian-Sheng

    2002-01-01

    A detailed kinetic study of triple helix formation was performed by surface plasmon resonance. Three systems were investigated involving 15mer pyrimidine oligonucleotides as third strands. Rate constants and activation energies were validated by comparison with thermodynamic values calculated from UV-melting analysis. Replacement of a T·A base pair by a C·G pair at either the 5′ or the 3′ end of the target sequence allowed us to assess mismatch effects and to delineate the mechanism of triple helix formation. Our data show that the association rate constant is governed by the sequence of base triplets on the 5′ side of the triplex (referred to as the 5′ side of the target oligopurine strand) and provides evidence that the reaction pathway for triple helix formation in the pyrimidine motif proceeds from the 5′ end to the 3′ end of the triplex according to the nucleation-zipping model. It seems that this is a general feature for all triple helices formation, probably due to the right-handedness of the DNA double helix that provides a stronger base stacking at the 5′ than at the 3′ duplex–triplex junction. Understanding the mechanism of triple helix formation is not only of fundamental interest, but may also help in designing better triple helix-forming oligonucleotides for gene targeting and control of gene expression. PMID:12490709

  4. Triple loop heat exchanger for an absorption refrigeration system

    DOEpatents

    Reimann, Robert C.

    1984-01-01

    A triple loop heat exchanger for an absorption refrigeration system is disclosed. The triple loop heat exchanger comprises portions of a strong solution line for conducting relatively hot, strong solution from a generator to a solution heat exchanger of the absorption refrigeration system, conduit means for conducting relatively cool, weak solution from the solution heat exchanger to the generator, and a bypass system for conducting strong solution from the generator around the strong solution line and around the solution heat exchanger to an absorber of the refrigeration system when strong solution builds up in the generator to an undesirable level. The strong solution line and the conduit means are in heat exchange relationship with each other in the triple loop heat exchanger so that, during normal operation of the refrigeration system, heat is exchanged between the relatively hot, strong solution flowing through the strong solution line and the relatively cool, weak solution flowing through the conduit means. Also, the strong solution line and the bypass system are in heat exchange relationship in the triple loop heat exchanger so that if the normal flow path of relatively hot, strong solution flowing from the generator to an absorber is blocked, then this relatively, hot strong solution which will then be flowing through the bypass system in the triple loop heat exchanger, is brought into heat exchange relationship with any strong solution which may have solidified in the strong solution line in the triple loop heat exchanger to thereby aid in desolidifying any such solidified strong solution.

  5. Triple X syndrome: a review of the literature.

    PubMed

    Otter, Maarten; Schrander-Stumpel, Constance T R M; Curfs, Leopold M G

    2010-03-01

    The developmental and clinical aspects in the literature on triple X syndrome are reviewed. Prenatal diagnosis depends on karyotyping. The incidence is 1 of 1000 females. At birth, 47,XXX girls have a lower mean birth weight and a smaller head circumference. Triple X diagnosis was not suspected at birth. The maternal age seems to be increased. Toddlers with triple X syndrome show delayed language development. The youngest girls show accelerated growth until puberty. EEG abnormalities seem to be rather common. Many girls show motor-coordination problems and auditory-processing disorders are not rare. Scoliosis is probably more common in adolescent cases. The IQ levels are 20 points below that of controls, and verbal IQ is lowest. The girls struggle with low self-esteem and they need psychological, behavioural and educational support. They perform best in stable families. After leaving school they seem to feel better. In adults, premature ovarian failure seems to be more prevalent than in controls. MRIs of the brain seem to show decreased brain volumes. The 47,XXX women most often find jobs that reflect their performance abilities. Psychotic illness seems to be more prevalent in triple X adult women than in controls. Psychotic disorders respond well to psychotropic drugs. Triple X adults suffer more frequently from cyclothymic and labile personality traits. Research on triple X syndrome may yield more insight into brain and behaviour relations, developmental psychopathology, auditory-processing disorders, EEG disorders, personality and psychotic disorders, etc. PMID:19568271

  6. Triple X syndrome: a review of the literature

    PubMed Central

    Otter, Maarten; Schrander-Stumpel, Constance TRM; Curfs, Leopold MG

    2010-01-01

    The developmental and clinical aspects in the literature on triple X syndrome are reviewed. Prenatal diagnosis depends on karyotyping. The incidence is 1 of 1000 females. At birth, 47,XXX girls have a lower mean birth weight and a smaller head circumference. Triple X diagnosis was not suspected at birth. The maternal age seems to be increased. Toddlers with triple X syndrome show delayed language development. The youngest girls show accelerated growth until puberty. EEG abnormalities seem to be rather common. Many girls show motor-coordination problems and auditory-processing disorders are not rare. Scoliosis is probably more common in adolescent cases. The IQ levels are 20 points below that of controls, and verbal IQ is lowest. The girls struggle with low self-esteem and they need psychological, behavioural and educational support. They perform best in stable families. After leaving school they seem to feel better. In adults, premature ovarian failure seems to be more prevalent than in controls. MRIs of the brain seem to show decreased brain volumes. The 47,XXX women most often find jobs that reflect their performance abilities. Psychotic illness seems to be more prevalent in triple X adult women than in controls. Psychotic disorders respond well to psychotropic drugs. Triple X adults suffer more frequently from cyclothymic and labile personality traits. Research on triple X syndrome may yield more insight into brain and behaviour relations, developmental psychopathology, auditory-processing disorders, EEG disorders, personality and psychotic disorders, etc. PMID:19568271

  7. Overexpression of Cell Cycle Progression Inhibitor Geminin is Associated with Tumor Stem-Like Phenotype of Triple-Negative Breast Cancer

    PubMed Central

    Di Bonito, Maurizio; Collina, Francesca; Scognamiglio, Giosuè; Cerrone, Margherita; La Mantia, Elvira; Barbato, Antonio; Liguori, Giuseppina; Botti, Gerardo

    2012-01-01

    Purpose Triple-negative breast cancer, has a significant clinical relevance being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. For this reason, identifying the molecular pathways associated with increased aggressiveness, for example the presence of stem cell populations within the tumor and alteration of genes associated with cell cycle regulation represents an important objective in the clinical research into this neoplasm. Methods To investigate the role of cell cycle progression inhibitor Geminin in triple-negative breast cancers and its potential correlation with stem-like phenotype of this neoplasm, we used tissue microarray technology to build a specific triple-negative breast cancer tissue micro-array. Geminin and cancer stem cell marker CD133 expression was further investigated at the mRNA level for selected breast tumor samples through realtime polymerase chain reaction quantification. Results Our results showed that CD133 expression was significantly associated to high Geminin expression (p=0.017), a strong association between Ki-67 and tumor grade (p=0.020) and an inverse association between Geminin expression and lymphonode metastases (p=0.058), and a trend of statistically significance between Geminin marker expression and survival of triple-negative breast cancer patients (p=0.076). Conclusion The strong association between the expression of CD133 and Geminin could be useful in molecular stratification of breast tumors and in particular of triple-negative breast cancers. PMID:22807933

  8. Triple positive breast cancer: a distinct subtype?

    PubMed

    Vici, Patrizia; Pizzuti, Laura; Natoli, Clara; Gamucci, Teresa; Di Lauro, Luigi; Barba, Maddalena; Sergi, Domenico; Botti, Claudio; Michelotti, Andrea; Moscetti, Luca; Mariani, Luciano; Izzo, Fiorentino; D'Onofrio, Loretta; Sperduti, Isabella; Conti, Francesca; Rossi, Valentina; Cassano, Alessandra; Maugeri-Saccà, Marcello; Mottolese, Marcella; Marchetti, Paolo

    2015-02-01

    Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets. PMID:25554445

  9. Predicted thermal performance of triple vacuum glazing

    SciTech Connect

    Fang, Yueping; Hyde, Trevor J.; Hewitt, Neil

    2010-12-15

    The simulated triple vacuum glazing (TVG) consists of three 4 mm thick glass panes with two vacuum gaps, with each internal glass surface coated with a low-emittance coating with an emittance of 0.03. The two vacuum gaps are sealed by an indium based sealant and separated by a stainless steel pillar array with a height of 0.12 mm and a pillar diameter of 0.3 mm spaced at 25 mm. The thermal transmission at the centre-of-glazing area of the TVG was predicted to be 0.26 W m{sup -2} K{sup -1}. The simulation results show that although the thermal conductivity of solder glass (1 W m{sup -1} K{sup -1}) and indium (83.7 W m{sup -1} K{sup -1}) are very different, the difference in thermal transmission of TVGs resulting from the use of an indium and a solder glass edge seal was 0.01 W m{sup -2} K{sup -1}. This is because the edge seal is so thin (0.12 mm), consequently there is a negligible temperature drop across it irrespective of the material that the seal is made from relative to the total temperature difference across the glazing. The results also show that there is a relatively large increase in the overall thermal conductance of glazings without a frame when the width of the indium edge seal is increased. Increasing the rebate depth in a solid wood frame decreased the heat transmission of the TVG. The overall heat transmission of the simulated 0.5 m by 0.5 m TVG was 32.6% greater than that of the 1 m by 1 m TVG, since heat conduction through the edge seal of the small glazing has a larger contribution to the total glazing heat transfer than that of the larger glazing system. (author)

  10. Features of triple-negative breast cancer

    PubMed Central

    Plasilova, Magdalena L.; Hayse, Brandon; Killelea, Brigid K.; Horowitz, Nina R.; Chagpar, Anees B.; Lannin, Donald R.

    2016-01-01

    Abstract The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC was present in 38,628 of 295,801 (13%) female patients compared to 185 of 3136 (6%) male patients (P < 0.001). The incidence of TNBC varied by region from 10.8% in New England to 15.8% in the east south central US (P < 0.001), as well as by race with the highest rates in African-Americans (23.7%), and lowest in Filipino patients (8.9%). The incidence of TNBC also varied by histology, accounting for 76% of metaplastic cancers, but only 2% of infiltrating lobular carcinomas. TNBCs were significantly larger than non-TNBC (mean 2.8 cm vs 2.1 cm, P < 0.001), and more TNBC were poorly differentiated compared to other subtypes (79.7% vs 25.8%, P < 0.001). On univariate analysis, TNBC was no more likely than non-TNBC to have node-positive disease (32.0% vs 31.7%, respectively, P = 0.218) but in a multivariable analysis controlling for tumor size and grade, TNBC was associated with significantly less node-positivity (OR = 0.59; 95% confidence interval [CI]: 0.57–0.60). TNBC has distinct features regarding age, gender, geographic, and racial distribution. Compared to non-TNBC, TNBC is larger and higher grade, but less likely to have lymph node metastases. PMID:27583878

  11. Laser speckle strain and deformation sensor using linear array image cross-correlation method for specifically arranged triple-beam triple-camera configuration

    NASA Technical Reports Server (NTRS)

    Sarrafzadeh-Khoee, Adel K. (Inventor)

    2000-01-01

    The invention provides a method of triple-beam and triple-sensor in a laser speckle strain/deformation measurement system. The triple-beam/triple-camera configuration combined with sequential timing of laser beam shutters is capable of providing indications of surface strain and structure deformations. The strain and deformation quantities, the four variables of surface strain, in-plane displacement, out-of-plane displacement and tilt, are determined in closed form solutions.

  12. Inhibition of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin

    SciTech Connect

    Wang, Feng; Yang, Yong

    2014-11-21

    Highlights: • Suppression of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin. • Repression of PKM2 affects the glycolysis and decreases ATP production. • Downregulation of PKM2 increases the intracellular accumulation of doxorubicin. • Inhibition of PKM2 enhances the antitumor efficacy of doxorubicin in vivo. - Abstract: Cancer cells alter regular metabolic pathways in order to sustain rapid proliferation. One example of metabolic remodeling in cancerous tissue is the upregulation of pyruvate kinase isoenzyme M2 (PKM2), which is involved in aerobic glycolysis. Indeed, PKM2 has previously been identified as a tumor biomarker and as a potential target for cancer therapy. Here, we examined the effects of combined treatment with doxorubicin and anti-PKM2 small interfering RNA (siRNA) on triple-negative breast cancer (TNBC). The suppression of PKM2 resulted in changes in glucose metabolism, leading to decreased synthesis of adenosine triphosphate (ATP). Reduced levels of ATP resulted in the intracellular accumulation of doxorubicin, consequently enhancing the therapeutic efficacy of this drug in several triple-negative breast cancer cell lines. Furthermore, the combined effect of PKM2 siRNA and doxorubicin was evaluated in an in vivo MDA-MB-231 orthotopic breast cancer model. The siRNA was systemically administered through a polyethylenimine (PEI)-based delivery system that has been extensively used. We demonstrate that the combination treatment showed superior anticancer efficacy as compared to doxorubicin alone. These findings suggest that targeting PKM2 can increase the efficacy of chemotherapy, potentially providing a new approach for improving the outcome of chemotherapy in patients with TNBC.

  13. Pursuing the Triple Aim: The First 7 Years

    PubMed Central

    Whittington, John W; Nolan, Kevin; Lewis, Ninon; Torres, Trissa

    2015-01-01

    Context In 2008, researchers at the Institute for Healthcare Improvement (IHI) described the Triple Aim as simultaneously “improving the individual experience of care; improving the health of populations; and reducing the per capita costs of care for populations.” IHI and its close colleagues had determined that both individual and societal changes were needed. Methods In 2007, IHI began recruiting organizations from around the world to participate in a collaborative to implement what became known as the Triple Aim. The 141 participating organizations included health care systems, hospitals, health care insurance companies, and others closely tied to health care. In addition, key groups outside the health care system were represented, such as public health agencies, social services groups, and community coalitions. This collaborative provided a structure for observational research. By noting the contrasts between the contexts and structures of those sites in the collaborative that progressed and those that did not, we were able to develop an ex post theory of what is needed for an organization or community to successfully pursue the Triple Aim. Findings Drawing on our 7 years of experience, we describe the 3 major principles that guided the organizations and communities working on the Triple Aim: creating the right foundation for population management, managing services at scale for the population, and establishing a learning system to drive and sustain the work over time. Conclusions The concept of the Triple Aim is now widely used, because of IHI's work with many organizations and also because of the adoption of the Triple Aim as part of the national strategy for US health care, developed during the implementation of the Patient Protection and Affordable Care Act of 2010. Even those organizations working on the Triple Aim before IHI coined the term found our concept to be useful because it helped them think about all 3 dimensions at once and organize their

  14. MicroRNAs Expression in Triple Negative vs Non Triple Negative Breast Cancer in Tunisia: Interaction with Clinical Outcome

    PubMed Central

    Medimegh, Imen; Omrane, Ines; Privat, Maud; Uhrhummer, Nancy; Ayari, Hajer; Belaiba, Fadoua; Benayed, Farhat; Benromdhan, Khaled; Mader, Sylvie; Bignon, Ives-Jean; Elgaaied, Amel Benammar

    2014-01-01

    Introduction MicroRNAs are small, non coding regulatory molecules containing approximately 21 to 25 nucleotides. They function as controllers of expression at post transcriptional levels of most human protein-coding genes and play an essential role in cell signaling pathways. The objective of the present study is to evaluate the expression profile of the following micro-RNAs: miR-10b, miR-17, miR-21, miR-34a, miR-146a, miR-148a and miR-182, and to determine their possible interaction in triple-negative and non triple-negative primary breast cancers based on clinical outcome. Methods 60 triple-negative and non triple-negative breast cancer cases, along with their corresponding normal samples were investigated in relation to the expression of the seven studied miRNAs using qPCR Syber Green. Results We observed that miR-21, miR-146a and miR-182 were significantly over expressed in triple negative breast cancer. Moreover, miR-10b, miR-21 and miR-182 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma while only miR-10b was associated with grade III in non triple negative breast cancer cases. Almost all the analyzed microRNAs were strongly associated with patients’ genico-obstetric history in non triple negative breast cancer cases except for miR-34a. All the studied microRNAs were strongly correlated with the use of the contraceptive pills in non triple negative breast cancer groups. The additive effect of hormonal factors in triple negative breast cancer cases showed an association with all the studied miRs except for miR-34 and miR-146a. Conclusion The studied microRNAs are strongly influenced by environmental factors especially with hormonal patients’ history. Moreover, miR-10b, miR-21 and miR-182 could be defined as biomarkers in breast cancer to predict both lymph node metastases and grade III occurrence. PMID:25369070

  15. Downregulation of microRNA-206 promotes invasion and angiogenesis of triple negative breast cancer.

    PubMed

    Liang, Zhongxing; Bian, Xuehai; Shim, Hyunsuk

    2016-08-26

    Triple negative breast tumors don't respond to Tamoxifen and Herceptin, two of the most effective medications for treating breast cancer. Additionally, triple negative breast cancer (TNBC) intrinsically resists or will eventually acquire resistance to chemotherapy. The purpose of this study is to understand better the molecular basis of TNBC as well as develop new therapeutic strategies against it. Here, we analyzed miRNA-206 expression levels in breast cancer cell lines and tissues. In addition, we investigated whether miR-206 mimics inhibited TNBC tumor invasion and angiogenesis. The results showed that miR-206 was downregulated in TNBC compared to non-TNBC cell lines and tissues. Additionally, the decreased levels of miR-206 were inversely consistent with expression levels of VEGF. Furthermore, the forced expression of miR-206 in the mimic-transfected TNBC cells downregulated VEGF, MAPK3, and SOX9 expression levels. The miR-206 mimics inhibited TNBC breast cell invasion and angiogenesis. These findings demonstrate for the first time the involvement of miRNA-206 in TNBC invasion and angiogenesis and suggest that miR-206 may be an efficient agent for therapy of TNBC. PMID:27318091

  16. Rational design of a triple reporter gene for multimodality molecular imaging.

    PubMed

    Hsieh, Ya-Ju; Hwu, Luen; Ke, Chien-Chih; Yeh, Skye Hsin-Hsien; Lin, Chien-Feng; Chen, Fu-Du; Wang, Hsin-Ell; Lin, Kang-Ping; Chen, Ran-Chou; Liu, Ren-Shyan

    2014-01-01

    Multimodality imaging using noncytotoxic triple fusion (TF) reporter genes is an important application for cell-based tracking, drug screening, and therapy. The firefly luciferase (fl), monomeric red fluorescence protein (mrfp), and truncated herpes simplex virus type 1 thymidine kinase SR39 mutant (ttksr39) were fused together to create TF reporter gene constructs with different order. The enzymatic activities of TF protein in vitro and in vivo were determined by luciferase reporter assay, H-FEAU cellular uptake experiment, bioluminescence imaging, and micropositron emission tomography (microPET). The TF construct expressed in H1299 cells possesses luciferase activity and red fluorescence. The tTKSR39 activity is preserved in TF protein and mediates high levels of H-FEAU accumulation and significant cell death from ganciclovir (GCV) prodrug activation. In living animals, the luciferase and tTKSR39 activities of TF protein have also been successfully validated by multimodality imaging systems. The red fluorescence signal is relatively weak for in vivo imaging but may expedite FACS-based selection of TF reporter expressing cells. We have developed an optimized triple fusion reporter construct DsRedm-fl-ttksr39 for more effective and sensitive in vivo animal imaging using fluorescence, bioluminescence, and PET imaging modalities, which may facilitate different fields of biomedical research and applications. PMID:24809057

  17. Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug Delivery.

    PubMed

    Zhang, Yuanyuan; Ang, Chung Yen; Li, Menghuan; Tan, Si Yu; Qu, Qiuyu; Luo, Zhong; Zhao, Yanli

    2015-08-19

    In this study, pH, reduction and light triple-responsive nanocarriers based on hollow mesoporous silica nanoparticles (HMSNs) modified with poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) were developed via surface-initiated atom transfer radical polymerization. Both reduction-cleavable disulfide bond and light-cleavable o-nitrobenzyl ester were used as the linkages between HMSNs and pH-sensitive PDEAEMA polymer caps. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and final nanocarriers. Doxorubicin (DOX) was easily encapsulated into the nanocarriers with a high loading capacity, and quickly released in response to the stimuli of reducing agent, acid environment or UV light irradiation. In addition, flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies indicated that the nanocarriers were efficiently internalized by HeLa cancer cells, exhibiting (i) enhanced release of DOX into the cytoplasm under external UV light irradiation, (ii) better cytotoxicity against HeLa cells, and (iii) superior control over drug delivery and release. Thus, the triple-responsive nanocarriers present highly promising potentials as a drug delivery platform for cancer therapy. PMID:26221866

  18. TRIPLE-STAR CANDIDATES AMONG THE KEPLER BINARIES

    SciTech Connect

    Rappaport, S.; Deck, K.; Sanchis-Ojeda, R.; Levine, A.; Borkovits, T.; Carter, J.; El Mellah, I.; Kalomeni, B. E-mail: kdeck@mit.edu E-mail: aml@space.mit.edu E-mail: jacarter@cfa.harvard.edu

    2013-05-01

    We present the results of a search through the photometric database of Kepler eclipsing binaries looking for evidence of hierarchical triple-star systems. The presence of a third star orbiting the binary can be inferred from eclipse timing variations. We apply a simple algorithm in an automated determination of the eclipse times for all 2157 binaries. The ''calculated'' eclipse times, based on a constant period model, are subtracted from those observed. The resulting O - C (observed minus calculated times) curves are then visually inspected for periodicities in order to find triple-star candidates. After eliminating false positives due to the beat frequency between the {approx}1/2 hr Kepler cadence and the binary period, 39 candidate triple systems were identified. The periodic O - C curves for these candidates were then fit for contributions from both the classical Roemer delay and so-called physical delay, in an attempt to extract a number of the system parameters of the triple. We discuss the limitations of the information that can be inferred from these O - C curves without further supplemental input, e.g., ground-based spectroscopy. Based on the limited range of orbital periods for the triple-star systems to which this search is sensitive, we can extrapolate to estimate that at least 20% of all close binaries have tertiary companions.

  19. Development of 600 kV triple resonance pulse transformer.

    PubMed

    Li, Mingjia; Zhang, Faqiang; Liang, Chuan; Xu, Zhou

    2015-06-01

    In this paper, a triple-resonance pulse transformer based on an air-core transformer is introduced. The voltage across the high-voltage winding of the air-core transformer is significantly less than the output voltage; instead, the full output voltage appears across the tuning inductor. The maximum ratio of peak load voltage to peak transformer voltage is 2.77 in theory. By analyzing pulse transformer's lossless circuit, the analytical expression for the output voltage and the characteristic equation of the triple-resonance circuit are presented. Design method for the triple-resonance pulse transformer (iterated simulation method) is presented, and a triple-resonance pulse transformer is developed based on the existing air-core transformer. The experimental results indicate that the maximum ratio of peak voltage across the load to peak voltage across the high-voltage winding of the air-core transformer is approximately 2.0 and the peak output voltage of the triple-resonance pulse transformer is approximately 600 kV. PMID:26133858

  20. Triple-star Candidates among the Kepler Binaries

    NASA Astrophysics Data System (ADS)

    Rappaport, S.; Deck, K.; Levine, A.; Borkovits, T.; Carter, J.; El Mellah, I.; Sanchis-Ojeda, R.; Kalomeni, B.

    2013-05-01

    We present the results of a search through the photometric database of Kepler eclipsing binaries looking for evidence of hierarchical triple-star systems. The presence of a third star orbiting the binary can be inferred from eclipse timing variations. We apply a simple algorithm in an automated determination of the eclipse times for all 2157 binaries. The "calculated" eclipse times, based on a constant period model, are subtracted from those observed. The resulting O - C (observed minus calculated times) curves are then visually inspected for periodicities in order to find triple-star candidates. After eliminating false positives due to the beat frequency between the ~1/2 hr Kepler cadence and the binary period, 39 candidate triple systems were identified. The periodic O - C curves for these candidates were then fit for contributions from both the classical Roemer delay and so-called physical delay, in an attempt to extract a number of the system parameters of the triple. We discuss the limitations of the information that can be inferred from these O - C curves without further supplemental input, e.g., ground-based spectroscopy. Based on the limited range of orbital periods for the triple-star systems to which this search is sensitive, we can extrapolate to estimate that at least 20% of all close binaries have tertiary companions.

  1. Spectra, triple, and quartic gauge couplings in a Higgsless model

    SciTech Connect

    Cheung Kingman; Wu Xiaohong; Yan Qishu

    2007-12-01

    Spectra, triple, and quartic gauge couplings of the Higgsless model with gauge group SU(2){sub L}xSU(2){sub R}xU(1){sub B-L} defined in warped space are explored with a numerical method. We extend the equation of motions, boundary conditions, and formalism of multi-gauge-boson vertices to the Hirn-Sanz scenario. By assuming the ideally delocalized fermion profile, we study the spectra of vector bosons as well as the triple and quartic gauge couplings among vector bosons. It is found that mass spectra can be greatly modified by the parameters of QCD power corrections. Meanwhile, the triple and quartic gauge couplings can deviate from the values of the standard model to at least {+-}10% and can saturate the LEP2 bounds. We find the triple gauge couplings of ZWW can be 50% smaller than the unitarity bounds. The triple gauge couplings of ZWW is 20% smaller than the unitarity bounds, which might challenge the detection of Z via s channel at LHC if m{sub Z}>500 GeV.

  2. Longitudinal Neuropsychological Profile in a Patient with Triple A Syndrome

    PubMed Central

    Mazzone, Luigi; Postorino, Valentina; De Peppo, Lavinia; Vassena, Lia; Fatta, Laura; Armando, Marco; Scirè, Giuseppe; Cappa, Marco; Vicari, Stefano

    2013-01-01

    Triple A syndrome is an autosomal recessive disorder characterized by the triad of adrenocorticotropic hormone resistant adrenal insufficiency, achalasia, and alacrima. Our aim was to describe the neuropsychological characteristics and the cooccurring psychopathological and neurological disorders in an Italian male child suffering from Triple A syndrome at the time of admission (T0) and after one year of follow-up (T1). Many difficulties were observed in the motor domain, as well as in manual dexterity and static/dynamic balance domains of the motor task over time. In sharp contrast with previous literature reports on frequent mild cognitive dysfunction in patients with Triple A syndrome, our child did not show any mental retardation. By contrast, he showed an average IQ at T0 with a slight improvement at T1. To our knowledge, this report is the first describing neuropsychological profile and co-occurring psychopathological problems in a child with Triple A syndrome. Considering that the Triple A syndrome is a progressive disorder which can take years to develop the full-blown clinical picture, these patients require periodical medical controls. Moreover, assessment of neuropsychological and psychopathological features should be performed in patients with this disease, in order to underline the variability of this syndrome. PMID:23691407

  3. Numerical Study of Buoyancy and Differential Diffusion Effects on the Structure and Dynamics of Triple Flames

    NASA Technical Reports Server (NTRS)

    Chen, J. -Y.; Echekki, T.

    1999-01-01

    Triple flames arise in a number of practical configurations where fuel and oxidizer are partially premixed, such as in the base of a lifted jet flame. Past experimental studies, theoretical analyses, and numerical modeling of triple flames suggested the potential role of triple flames in stabilizing turbulent flames and in promoting flame propagation. From recent numerical simulations of laminar triple flames, a strong influence of differential diffusion among species and heat on the triple flame structure has been gradually appreciated. This paper reports preliminary numerical results on the influence of gravity and differential diffusion effects on the structure and dynamics of triple flames with a one-step global irreversible chemistry model.

  4. Differential cytotoxic and radiosensitizing effects of silver nanoparticles on triple-negative breast cancer and non-triple-negative breast cells

    PubMed Central

    Swanner, Jessica; Mims, Jade; Carroll, David L; Akman, Steven A; Furdui, Cristina M; Torti, Suzy V; Singh, Ravi N

    2015-01-01

    Identification of differential sensitivity of cancer cells as compared to normal cells has the potential to reveal a therapeutic window for the use of silver nanoparticles (AgNPs) as a therapeutic agent for cancer therapy. Exposure to AgNPs is known to cause dose-dependent toxicities, including induction of oxidative stress and DNA damage, which can lead to cell death. Triple-negative breast cancer (TNBC) subtypes are more vulnerable to agents that cause oxidative stress and DNA damage than are other breast cancer subtypes. We hypothesized that TNBC may be susceptible to AgNP cytotoxicity, a potential vulnerability that could be exploited for the development of new therapeutic agents. We show that AgNPs are highly cytotoxic toward TNBC cells at doses that have little effect on nontumorigenic breast cells or cells derived from liver, kidney, and monocyte lineages. AgNPs induced more DNA and oxidative damage in TNBC cells than in other breast cells. In vitro and in vivo studies showed that AgNPs reduce TNBC growth and improve radiation therapy. These studies show that unmodified AgNPs act as a self-therapeutic agent with a combination of selective cytotoxicity and radiation dose-enhancement effects in TNBC at doses that are nontoxic to noncancerous breast and other cells. PMID:26185437

  5. Triple jeopardy for HIV: substance using Severely Mentally Ill Adults.

    PubMed

    Devieux, Jessy G; Malow, Robert; Lerner, Brenda G; Dyer, Janyce G; Baptista, Ligia; Lucenko, Barbara; Kalichman, Seth

    2007-01-01

    Severely Mentally Ill (SMI) adults have disproportionately high HIV seroprevalence rates. Abuse of alcohol and other substances (AOD) and lifetime exposure to trauma by others are particularly potent risk factors, which, in combination with psychiatric disabilities, create triple jeopardy for HIV infection. This study examined the predictive utility of demographic characteristics; history of physical, emotional, or sexual abuse; extent of drug and alcohol abuse; knowledge about HIV/AIDS; sexual self-efficacy; and condom attitudes toward explaining the variance in a composite of HIV high-risk behavior among 188 SMI women and 158 SMI men. History of sexual abuse, engaging in sexual activities while high on substances, and lower cannabis use were the most significant predictors of HIV sexual risk behaviors. Given the triple jeopardy for HIV risk in this population, a triple barreled approach that simultaneously addresses multiple health risks within an integrated treatment setting is warranted. PMID:17298927

  6. Triple and quartic gauge couplings at LEP 2

    NASA Astrophysics Data System (ADS)

    Brunelière, R.

    We review the status of published and preliminary measurements of triple and quartic gauge boson couplings from the four LEP experiments. Charged current triple gauge boson couplings (WWZ and WWγ) are measured using W-pair, single-W and single-γ productions with the data collected between 1997 and 2000 (700\\ pb-1 per experiment). Neutral current triple gauge boson couplings are studied with Zγ (Zγγ* and ZγZ* vertices) and ZZ (ZZγ* and ZZZ* vertices) events. Limits on anomalous quartic gauge boson couplings with at least one photon (WWγγ, WWZγ and ZZγγ) are set from WWγ, q¯ {q}γ γ and ν ¯ {ν }γ γ events. No strong deviations from the Standard Model expectations are found.

  7. On universality of scaling law describing roughness of triple line.

    PubMed

    Bormashenko, Edward; Musin, Albina; Whyman, Gene; Barkay, Zahava; Zinigrad, Michael

    2015-01-01

    The fine structure of the three-phase (triple) line was studied for different liquids, various topographies of micro-rough substrates and various wetting regimes. Wetting of porous and pillar-based micro-scaled polymer surfaces was investigated. The triple line was visualized with the environmental scanning electron microscope and scanning electron microscope for the "frozen" triple lines. The value of the roughness exponent ζ for water (ice)/rough polymer systems was located within 0.55-0.63. For epoxy glue/rough polymer systems somewhat lower values of the exponent, 0.42 < ζ < 0.54, were established. The obtained values of ζ were close for the Cassie and Wenzel wetting regimes, different liquids, and different substrates' topographies. Thus, the above values of the exponent are to a great extent universal. The switch of the exponent, when the roughness size approaches to the correlation length of the defects, is also universal. PMID:25618613

  8. THE ALGOL TRIPLE SYSTEM SPATIALLY RESOLVED AT OPTICAL WAVELENGTHS

    SciTech Connect

    Zavala, R. T.; Hutter, D. J.; Hummel, C. A.; Boboltz, D. A.; Ojha, R.; Shaffer, D. B.; Tycner, C.; Richards, M. T. E-mail: djh@nofs.navy.mi E-mail: dboboltz@usno.navy.mi E-mail: shaffer@alumni.caltech.ed E-mail: mrichards@astro.psu.ed

    2010-05-20

    Interacting binaries typically have separations in the milliarcsecond regime, and hence it has been challenging to resolve them at any wavelength. However, recent advances in optical interferometry have improved our ability to discern the components in these systems and have now enabled the direct determination of physical parameters. We used the Navy Prototype Optical Interferometer to produce for the first time images resolving all three components in the well-known Algol triple system. Specifically, we have separated the tertiary component from the binary and simultaneously resolved the eclipsing binary pair, which represents the nearest and brightest eclipsing binary in the sky. We present revised orbital elements for the triple system, and we have rectified the 180{sup 0} ambiguity in the position angle of Algol C. Our directly determined magnitude differences and masses for this triple star system are consistent with earlier light curve modeling results.

  9. A microelectromechanical systems-enabled, miniature triple quadrupole mass spectrometer.

    PubMed

    Wright, Steven; Malcolm, Andrew; Wright, Christopher; O'Prey, Shane; Crichton, Edward; Dash, Neil; Moseley, Richard W; Zaczek, Wojciech; Edwards, Peter; Fussell, Richard J; Syms, Richard R A

    2015-03-17

    Miniaturized mass spectrometers are becoming increasingly capable, enabling the development of many novel field and laboratory applications. However, to date, triple quadrupole tandem mass spectrometers, the workhorses of quantitative analysis, have not been significantly reduced in size. Here, the basis of a field-deployable triple quadrupole is described. The key development is a highly miniaturized ion optical assembly in which a sequence of six microengineered components is employed to generate ions at atmospheric pressure, provide a vacuum interface, effect ion guiding, and perform fragmentation and mass analysis. Despite its small dimensions, the collision cell efficiently fragments precursor ions and yields product ion spectra that are very similar to those recorded using conventional instruments. The miniature triple quadrupole has been used to detect thiabendazole, a common pesticide, in apples at a level of 10 ng/g. PMID:25708099

  10. Mesoscopic resonating valence bond system on a triple dot.

    PubMed

    Le Hur, Karyn; Recher, Patrik; Dupont, Emilie; Loss, Daniel

    2006-03-17

    We theoretically introduce a mesoscopic pendulum from a triple dot. The pendulum is fastened through a singly occupied dot (spin qubit). Two other strongly capacitively coupled islands form a double-dot charge qubit with one electron in excess oscillating between the two low-energy charge states (1,0) and (0,1). The triple dot is placed between two superconducting leads. Under realistic conditions, the main proximity effect stems from the injection of resonating singlet (valence) bonds on the triple dot. This gives rise to a Josephson current that is charge- and spin-dependent and, as a consequence, exhibits a distinct resonance as a function of the superconducting phase difference. PMID:16605773

  11. Adjuvant systemic treatment for individual patients with triple negative breast cancer.

    PubMed

    Oakman, Catherine; Moretti, Erica; Galardi, Francesca; Biagioni, Chiara; Santarpia, Libero; Biganzoli, Laura; Di Leo, Angelo

    2011-10-01

    Chemotherapy is the only evidence based adjuvant systemic treatment option in triple negative breast cancer (TNBC). Despite emerging results for targeted biological therapies for this subpopulation, lack of robust results does not currently support their use beyond the confines of a clinical trial. Conventional systemic chemotherapy remains the standard of care and is curative in a minority of patients. There is no defined standard chemotherapy and there is currently no robust, prospective, randomized data to advise different use of specific chemotherapy agents in TNBC as compared to non-TNBC. Data suggest high sensitivity to chemotherapy, however it is yet to be determined whether this increased sensitivity is agent/regimen specific or whether it reflects general chemosensitivity. This review will focus on systemic chemotherapy in early TNBC, particularly anthracyclines and platinums, and potential predictive tools to guide chemotherapy use. PMID:22015281

  12. Approach to the Triple Negative Breast Cancer in New Drugs Area

    PubMed Central

    Mirzania, Mehrzad

    2016-01-01

    Triple negative breast cancers (TNBCs) are associated with aggressive course, higher rates of visceral and central nervous system metastases and lower survival rate than hormone receptor positive. Once metastasis has occurred, a median survival was approximately one year. Currently, chemotherapy in TNBC is similar to other HER2- negative breast cancers but in the near future, it will revolutionize. TNBCs are quite heterogeneous based on biomarkers and genetic variations. The series of new drugs have been tried; in this article, platinum, anti-epigenetic drugs, PARP inhibitors, epidermal growth factor receptor inhibitor, Src family kinase inhibitor, anti androgen, glycoprotein Non-metastatic melanoma B (gpNMB) antibody, LHRH conjugated to cytotoxic drugs and inhibition of the PI3K/AKT/mTOR pathway will be explained. What is the optimal therapy for TNBC patients? It is still not clear but it seems that the road map according to biological and genetic markers is taking shape. PMID:27252813

  13. A comprehensive study of the Kepler triples via eclipse timing

    NASA Astrophysics Data System (ADS)

    Borkovits, T.; Hajdu, T.; Sztakovics, J.; Rappaport, S.; Levine, A.; Bíró, I. B.; Klagyivik, P.

    2016-02-01

    We produce and analyse eclipse time variation (ETV) curves for some 2600 Kepler binaries. We find good to excellent evidence for a third body in 222 systems via either the light-travel-time (LTTE) or dynamical effect delays. Approximately half of these systems have been discussed in previous work, while the rest are newly reported here. Via detailed analysis of the ETV curves using high-level analytic approximations, we are able to extract system masses and information about the three-dimensional characteristics of the triple for 62 systems which exhibit both LTTE and dynamical delays; for the remaining 160 systems, we give improved LTTE solutions. New techniques of pre-processing the flux time series are applied to eliminate false positive triples and to enhance the ETV curves. The set of triples with outer orbital periods shorter than ˜2000 d is now sufficiently numerous for meaningful statistical analysis. We find that (i) there is a peak near im ≃ 40° in the distribution of the triple versus inner binary mutual inclination angles that provides strong confirmation of the operation of Kozai-Lidov cycles with tidal friction; (ii) the median eccentricity of the third-body orbits is e2 = 0.35; (iii) there is a deficit of triple systems with binary periods ≲1 d and outer periods between ˜50 and 200 d which might help guide the refinement of theories of the formation and evolution of close binaries; and (iv) the substantial fraction of Kepler binaries which have third-body companions is consistent with a very large fraction of all binaries being part of triples.

  14. Healing of a large periapical lesion using triple antibiotic paste and intracanal aspiration in nonsurgical endodontic retreatment

    PubMed Central

    Dhillon, Jaidev Singh; Amita; Saini, Suresh Kumar; Bedi, Harmandeep Singh; Ratol, Sukhmilap Singh; Gill, Bobbin

    2014-01-01

    A patient with a large periapical lesion in relation to the maxillary right central and lateral incisors is presented here. During the conservative root canal treatment, aspiration of the fluid was done through the root canal, followed by placement of triple antibiotic paste for two weeks. Complete periapical healing was observed at the 24-month recall. This report confirms that for treatment of a large periapical lesion it is not always necessary to do surgical treatment and even cyst-like periapical lesions heal following conservative endodontic therapy. PMID:25565747

  15. Quaternary Evolution of Karliova Triple Junction

    NASA Astrophysics Data System (ADS)

    Sançar, Taylan; Zabcı, Cengiz; Akyüz, H. Serdar

    2013-04-01

    The arguments to explain Quaternary evolution of Karlıova Triple Junction (KTJ) depends upon two different analogue models. The compressional type of Prandtl Cell Model (PCM) and 60 km wide shear zone with concomitant counter clockwise block rotation used to modelled for west and east of the KTJ respectively. The data for the model of west of the KTJ acquired by extensive field studies, and quantified geomorphic features. Compressional PCM put forward that behavior of slip lines controlled by boundary faults. But the model is not enough to explain slip distribution, age relation of them. At west of the KTJ boundary faults presented by eastern most segments of the North Anatolian Fault Zone (NAFZ) and the East Anatolian Fault Zone (EAFZ). Slip lines, however, presented by Bahçeli and Toklular faults. Both field studies and morphometric analyses undisputedly set forth that there are two different fault types between the NAFZ and EAFZ. The most strain loaded fault type, which are positioned near the NAFZ, start as a strike-slip fault and when it turn to SE its sense of motion change to oblique normal due to changing orientation of principal stress axes. The new orientation of stress axes exposed in the field as a special kind of caprock -cuesta-. The younger slip lines formed very close to junction point and accommodate less slip. Even though slip trajectories started from the boundary faults in compressional PCM, at the west of KTJ, right lateral trajectories more clearly formed close the NAFZ and left lateral trajectories, relatively less strain loaded fault type, are poorly formed close the EAFZ . We think that, this differences between KTJ and compressional PCM result from the distinction of velocity of boundary faults. East of the KTJ governed by completely different mechanism. The region controlled two main fault systems. The Varto Fault Zone (VFZ), the eastern branch of the KTJ, and Murat Fault (MF) delimited the region from north and south respectively. The

  16. Triple-mode squeezing with dressed six-wave mixing

    NASA Astrophysics Data System (ADS)

    Wen, Feng; Li, Zepei; Zhang, Yiqi; Gao, Hong; Che, Junling; Che, Junling; Abdulkhaleq, Hasan; Zhang, Yanpeng; Wang, Hongxing

    2016-05-01

    The theory of proof-of-principle triple-mode squeezing is proposed via spontaneous parametric six-wave mixing process in an atomic-cavity coupled system. Special attention is focused on the role of dressed state and nonlinear gain on triple-mode squeezing process. Using the dressed state theory, we find that optical squeezing and Autler-Towns splitting of cavity mode can be realized with nonlinear gain, while the efficiency and the location of maximum squeezing point can be effectively shaped by dressed state in atomic ensemble. Our proposal can find applications in multi-channel communication and multi-channel quantum imaging.

  17. Non-resonant triple alpha reaction rate at low temperature

    SciTech Connect

    Itoh, T.; Tamii, A.; Aoi, N.; Fujita, H.; Hashimoto, T.; Miki, K.; Ogata, K.; Carter, J.; Donaldson, L.; Sideras-Haddad, E.; Furuno, T.; Kawabata, T.; Kamimura, M.; Nemulodi, F.; Neveling, R.; Smit, F. D.; Swarts, C.

    2014-05-02

    Our experimental goal is to study the non-resonant triple alpha reaction rate at low temperture (T < 10{sup 8} K). The {sup 13}C(p,d) reaction at 66 MeV has been used to probe the alpha-unbound continuum state in {sup 12}C just below the 2{sup nd} 0{sup +} state at 7.65 MeV. The transition strength to the continuum state is predicted to be sensitive to the non-resonant triple alpha reaction rate. The experiment has been performed at iThemba LABS. We report the present status of the experiment.

  18. Triple-mode squeezing with dressed six-wave mixing.

    PubMed

    Wen, Feng; Li, Zepei; Zhang, Yiqi; Gao, Hong; Che, Junling; Che, Junling; Abdulkhaleq, Hasan; Zhang, Yanpeng; Wang, Hongxing

    2016-01-01

    The theory of proof-of-principle triple-mode squeezing is proposed via spontaneous parametric six-wave mixing process in an atomic-cavity coupled system. Special attention is focused on the role of dressed state and nonlinear gain on triple-mode squeezing process. Using the dressed state theory, we find that optical squeezing and Autler-Towns splitting of cavity mode can be realized with nonlinear gain, while the efficiency and the location of maximum squeezing point can be effectively shaped by dressed state in atomic ensemble. Our proposal can find applications in multi-channel communication and multi-channel quantum imaging. PMID:27169878

  19. Triple-mode squeezing with dressed six-wave mixing

    PubMed Central

    Wen, Feng; Li, Zepei; Zhang, Yiqi; Gao, Hong; Che, Junling; Che, Junling; Abdulkhaleq, Hasan; Zhang, Yanpeng; Wang, Hongxing

    2016-01-01

    The theory of proof-of-principle triple-mode squeezing is proposed via spontaneous parametric six-wave mixing process in an atomic-cavity coupled system. Special attention is focused on the role of dressed state and nonlinear gain on triple-mode squeezing process. Using the dressed state theory, we find that optical squeezing and Autler-Towns splitting of cavity mode can be realized with nonlinear gain, while the efficiency and the location of maximum squeezing point can be effectively shaped by dressed state in atomic ensemble. Our proposal can find applications in multi-channel communication and multi-channel quantum imaging. PMID:27169878

  20. Charge frustration in a triangular triple quantum dot.

    PubMed

    Seo, M; Choi, H K; Lee, S-Y; Kim, N; Chung, Y; Sim, H-S; Umansky, V; Mahalu, D

    2013-01-25

    We experimentally investigate the charge (isospin) frustration induced by a geometrical symmetry in a triangular triple quantum dot. We observe the ground-state charge configurations of sixfold degeneracy, the manifestation of the frustration. The frustration results in omnidirectional charge transport, and it is accompanied by nearby nontrivial triple degenerate states in the charge stability diagram. The findings agree with a capacitive interaction model. We also observe unusual transport by the frustration, which might be related to elastic cotunneling and the interference of trajectories through the dot. This work demonstrates a unique way of studying geometrical frustration in a controllable way. PMID:25166188

  1. miRNAs and Other Epigenetic Changes as Biomarkers in Triple Negative Breast Cancer

    PubMed Central

    Mathe, Andrea; Scott, Rodney J.; Avery-Kiejda, Kelly A.

    2015-01-01

    Triple negative breast cancer (TNBC) is characterised by the lack of receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2). Since it cannot be treated by current endocrine therapies which target these receptors and due to its aggressive nature, it has one of the worst prognoses of all breast cancer subtypes. The only treatments remain chemo- and/or radio-therapy and surgery and because of this, novel biomarkers or treatment targets are urgently required to improve disease outcomes. MicroRNAs represent an attractive candidate for targeted therapies against TNBC, due to their natural ability to act as antisense interactors and regulators of entire gene sets involved in malignancy and their superiority over mRNA profiling to accurately classify disease. Here we review the current knowledge regarding miRNAs as biomarkers in TNBC and their potential use as therapeutic targets in this disease. Further, we review other epigenetic changes and interactions of these changes with microRNAs in this breast cancer subtype, which may lead to the discovery of new treatment targets for TNBC. PMID:26633365

  2. Standard of Care and Promising New Agents for Triple Negative Metastatic Breast Cancer

    PubMed Central

    Mancini, Patrizia; Angeloni, Antonio; Risi, Emanuela; Orsi, Errico; Mezi, Silvia

    2014-01-01

    Triple negative breast cancer (TNBC) is a cluster of heterogeneous diseases, all of them sharing the lack of expression of estrogen and progesterone receptors and HER2 protein. They are characterized by different biological, molecular and clinical features, including a poor prognosis despite the increased sensitivity to the current cytotoxic therapies. Several studies have identified important molecular features which enable further subdivision of this type of tumor. We are drawing from genomics, transcription and translation analysis at different levels, to improve our knowledge of the molecular alterations along the pathways which are activated during carcinogenesis and tumor progression. How this information should be used for the rational selection of therapy is an ongoing challenge and the subject of numerous research studies in progress. Currently, the vascular endothelial growth factor (VEGF), poly (ADP-ribose) polymerase (PARP), HSP90 and Aurora inhibitors are most used as targeting agents in metastatic setting clinical trials. In this paper we will review the current knowledge about the genetic subtypes of TNBC and their different responses to conventional therapeutic strategies, as well as to some new promising molecular target agents, aimed to achieve more tailored therapies. PMID:25347122

  3. A new photometric study of the triple star system EF Draconis

    NASA Astrophysics Data System (ADS)

    Yang, Yuan-Gui

    2012-04-01

    We present new charge-coupled device (CCD) photometry for the triple star EF Draconis, obtained in 2009 and 2011. Using the updated Wilson-Devinney program, the photometric solutions were deduced from two sets of light curves. The results indicate that EF Dra is an A-type W UMa binary with a contact degree of f = 46.7%(±0.6%) and a third light of l3 ≃ 1.5%. Through analyzing the O — C curve, it is found that the orbital period shows a long-time increase with a light-time orbit. The period, semi-amplitude and eccentricity of the third body are Pmod = 17.20(±0.18) yr, A = 0.0039d(±0.0002d) and e = 0.49(±0.02) respectively. This kind of tertiary companion may extract angular momentum from the central system. The orbital period of EF Dra secularly increases at a rate of dP/dt = +3.72(±0.07) × 10-7 d yr-1, which may be interpreted by mass transfer from the less massive to the more massive component. As period increases, the separation between components may increase, which will cause the contact degree to decrease. With mass transferring, the spin angular momentum will increase, while the orbital angular momentum will decrease. Only if the contact configuration would merge at could this kind of deep-contact binary with period increasing, such as EF Dra, evolve into a rapidly-rotating single star.

  4. P53 mutations in triple negative breast cancer upregulate endosomal recycling of epidermal growth factor receptor (EGFR) increasing its oncogenic potency.

    PubMed

    Shapira, Iuliana; Lee, Annette; Vora, Reena; Budman, Daniel R

    2013-11-01

    There is no available targeted therapy for triple-negative or its more aggressive subtype, basal-like breast cancer. Multiple therapeutic strategies based on translational knowledge have not improved the treatment options for triple negative patients. As understanding of molecular pathways that drive tumor development is rapidly increasing, it is imperative to adapt our treatment strategies to perturbations in molecular pathways driving the malignant process. Basal-like breast cancers over-express EGFR (without mutations or EGFR gene amplifications) and have p53 mutations. While EGFR drives the malignant behavior in triple negative breast cancer (TNBC), anti-EGFR therapies have fallen short of the expected results in clinical trials. Here we bring evidence that the less than optimal results of the anti-EGFR therapies may be explained in part by the increased potency of the EGFR signaling due to increased endosomal recycling. The functional connection between EGFR and endosomal trafficking in TNBC is mutant p53 found in the most aggressive forms of TNBC. Mutant p53 acquires oncogenic functions and binds p63 protein, a member of p53 family with tumor suppressor activities. In the absence of functional p63 there is an upregulation of endosomal recycling EGFR and integrin to the membrane with increased proinvasive abilities of cancer cells. Blocking endosomal trafficking combined with anti-EGFR treatments may result in better clinical outcomes in TNBC. PMID:23755891

  5. TH-C-BRD-04: Beam Modeling and Validation with Triple and Double Gaussian Dose Kernel for Spot Scanning Proton Beams

    SciTech Connect

    Hirayama, S; Takayanagi, T; Fujii, Y; Fujimoto, R; Fujitaka, S; Umezawa, M; Nagamine, Y; Hosaka, M; Yasui, K; Toshito, T

    2014-06-15

    Purpose: To present the validity of our beam modeling with double and triple Gaussian dose kernels for spot scanning proton beams in Nagoya Proton Therapy Center. This study investigates the conformance between the measurements and calculation results in absolute dose with two types of beam kernel. Methods: A dose kernel is one of the important input data required for the treatment planning software. The dose kernel is the 3D dose distribution of an infinitesimal pencil beam of protons in water and consists of integral depth doses and lateral distributions. We have adopted double and triple Gaussian model as lateral distribution in order to take account of the large angle scattering due to nuclear reaction by fitting simulated inwater lateral dose profile for needle proton beam at various depths. The fitted parameters were interpolated as a function of depth in water and were stored as a separate look-up table for the each beam energy. The process of beam modeling is based on the method of MDACC [X.R.Zhu 2013]. Results: From the comparison results between the absolute doses calculated by double Gaussian model and those measured at the center of SOBP, the difference is increased up to 3.5% in the high-energy region because the large angle scattering due to nuclear reaction is not sufficiently considered at intermediate depths in the double Gaussian model. In case of employing triple Gaussian dose kernels, the measured absolute dose at the center of SOBP agrees with calculation within ±1% regardless of the SOBP width and maximum range. Conclusion: We have demonstrated the beam modeling results of dose distribution employing double and triple Gaussian dose kernel. Treatment planning system with the triple Gaussian dose kernel has been successfully verified and applied to the patient treatment with a spot scanning technique in Nagoya Proton Therapy Center.

  6. Cases of Pregnant U.S. Women with Zika Triple Under New Counting Method

    MedlinePlus

    ... 158953.html Cases of Pregnant U.S. Women With Zika Triple Under New Counting Method Two registries will ... women in the United States infected with the Zika virus has just tripled because cases are now ...

  7. Makeup of Germs in Newborn's Gut May Triple Allergy, Asthma Risk

    MedlinePlus

    ... of Germs in Newborn's Gut May Triple Allergy, Asthma Risk Study finds abnormality present in 10 percent ... gut may triple the risk for allergies and asthma in childhood, new research warns. Millions of bacteria ...

  8. Stellar evolution and the triple-α reactions

    SciTech Connect

    Suda, Takuma

    2014-05-02

    Nuclear reaction rates play a crucial role in the evolution of stars. For low-mass stars, the triple-α reaction controls the helium burning stars in the red giant and asymptotic giant branch (AGB) phase. More importantly, the cross section of the triple-α reaction has a great impact on the helium ignition at the center of the electron degenerate helium core of red giants and on the helium shell flashes of AGB stars. It is to be noted that stellar evolution models are influenced not only by the value of the cross section, but also by the temperature dependence of the reaction rate. In this paper, I present the impact of the triple-α reaction rates on the evolution of low-mass metal-free stars and intermediate-mass AGB stars. According to the previous study, the constraint on the triple-α reaction rate is derived based on stellar evolution theory. It is found that the recent revisions of the rate proposed by nuclear physics calculations satisfy the condition for the ignition of the helium core flash in low-mass stars.

  9. 12. Photocopy of photograph. TRIPLE TRUSS BRIDGE OVER LITTLE SHENANGO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Photocopy of photograph. TRIPLE TRUSS BRIDGE OVER LITTLE SHENANGO RIVER ON COLLEGE (THEN PRAIRIE) AVENUE, CA. 1874. (Original in Greenville Area Historical Society) - College Avenue Bridge, Pennsylvania Route 58/ Legislative Route 82 spanning Little Shenango River, Greenville, Mercer County, PA

  10. Structural constraints regulating triple helix formation by A-tracts.

    PubMed

    Sen, A; Gräslund, A

    2000-12-15

    The study concerns the propensity of triple helix formation by different DNA oligonucleotides containing long A-tracts with and without flanking GxC base pairs in order to probe the role of length of the A-tract and the flanking sequences. From nuclear magnetic resonance (NMR) studies of imino proton spectra and circular dichroism (CD) spectroscopy of samples composed of potential triplex forming strand sequences in correct stoichiometries, we have concluded that 8-mer A-tracts flanked by GxC base pairs exert significant steric hindrance to triple helix formation. When as much as 50 mM Mg2+ was added, no triple helix formation was observed in these samples. In contrast, open-ended 8-mer A-tracts formed triplex with the corresponding two T8 strands under relatively mild ionic conditions (100 mM Na+). Moreover, the shorter the length of the A-tract, the less is the hindrance to form a triple helix. PMID:11152277

  11. Recent advances in (soil moisture) triple collocation analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To date, triple collocation (TC) analysis is one of the most important methods for the global scale evaluation of remotely sensed soil moisture data sets. In this study we review existing implementations of soil moisture TC analysis as well as investigations of the assumptions underlying the method....

  12. Residential Density: The Effects of Tripling College Students

    ERIC Educational Resources Information Center

    Clark, Elizabeth A.; Jackson, Shannon; Everhart, Deborah

    2012-01-01

    Due to a greater number of students enrolling in higher educational institutions, an increase in demand for housing on college campuses exists putting a strain on infrastructure. In order to accommodate the students, some universities are tripling students in residential settings by putting three students in a room originally designed for two.…

  13. Hindfoot Deformity Corrected With Double Versus Triple Arthrodesis: Radiographic Comparison.

    PubMed

    DeVries, J George; Scharer, Brandon

    2015-01-01

    Hindfoot fusion is capable of correcting hindfoot deformities. Typically, this has been done through triple arthrodesis. Recently, there has been some discussion of a double arthrodesis, sparing the calcaneocuboid joint. We compared the radiographic corrective ability of these 2 fusion techniques. A retrospective radiographic review was performed of 20 consecutive triple arthrodeses (triple) and 20 consecutive talonavicular and subtalar arthrodesis with calcaneocuboid preservation (double). Additional midfoot arthrodesis or osteotomy was performed as needed in each group. The preoperative measurements were compared to those from standing weightbearing films after fusion postoperatively. The angular measurements included the anteroposterior and lateral talar–first metatarsal line (Meary's and Simmons) and the anteroposterior and lateral talocalcaneal angle. Both groups demonstrated a statistically significant reduction in deformity and a return to more normal radiographic findings after arthrodesis (p < .05). The 2 groups did not differ statistically in preoperative deformity or correction obtained (p > .05). Traditionally, triple arthrodesis has been advocated for significant hindfoot deformity that is irreducible. Recent studies have questioned the need for inclusion of the calcaneocuboid joint in the arthrodesis, in particular, in a pronated, valgus-type foot. In addition, others have advocated a strictly medial approach to hindfoot fusion, necessarily avoiding the calcaneocuboid joint. Our findings agree with the assertion that hindfoot deformity can be adequately and reliably corrected through hindfoot arthrodesis whether or not the calcaneocuboid joint is included. PMID:25432460

  14. Quadrupolar, Triple [Delta]-Function Potential in One Dimension

    ERIC Educational Resources Information Center

    Patil, S. H.

    2009-01-01

    The energy and parity eigenstates for quadrupolar, triple [delta]-function potential are analysed. Using the analytical solutions in specific domains, simple expressions are obtained for even- and odd-parity bound-state energies. The Heisenberg uncertainty product is observed to have a minimum for a specific strength of the potential. The…

  15. Triple effect absorption chiller utilizing two refrigeration circuits

    DOEpatents

    DeVault, Robert C.

    1988-01-01

    A triple effect absorption method and apparatus having a high coefficient of performance. Two single effect absorption circuits are combined with heat exchange occurring between a condenser and absorber of a high temperature circuit, and a generator of a low temperature circuit. The evaporators of both the high and low temperature circuits provide cooling to an external heat load.

  16. Beyond triple collocation: Applications to satellite soil moisture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Triple collocation is now routinely used to resolve the exact (linear) relationships between multiple measurements and/or representations of a geophysical variable that are subject to errors. It has been utilized in the context of calibration, rescaling and error characterisation to allow comparison...

  17. Triple-stack multigap resistive plate chamber with strip readout

    NASA Astrophysics Data System (ADS)

    Babkin, V.; Basilev, S.; Buryakov, M.; Golovatyuk, V.; Lobastov, S.; Petrov, V.; Rumyantsev, M.; Schipunov, A.; Shutov, A.; Slepnev, I.; Slepnev, V.

    2016-07-01

    A triple-stack MRPC for the TOF system of the BM@N and the MPD experiments at the future collider NICA was tested. We use three stacks of glass to have symmetrical construction which allows to decrease dispersion and reflections of the signal from the readout strip.

  18. Software for goniometer control in the Triple Ion Implantation Facility

    SciTech Connect

    Allen, W.R.

    1994-02-01

    A computer program is described tat controls the goniometer employed in the ion scattering chamber of the Triple Ion Implantation Facility (TIF) in the Metals and Ceramics Division at Oak Ridge National Laboratory. Details of goniometer operation and its incorporation into the ion scattering setup specific to the TIF are also discussed.

  19. Subtalar versus triple arthrodesis after intra-articular calcaneal fractures

    PubMed Central

    Kieboom, Brenda C. T.; Bessems, Gert H. J. M.; Vogels, Lucas M. M.; van Lieshout, Esther M. M.; Patka, Peter

    2010-01-01

    Depending upon initial treatment, between 2 and 30% of patients with a displaced intra-articular calcaneal fracture require a secondary arthrodesis. The aim of this study was to investigate the effect of subtalar versus triple arthrodesis on functional outcome. A total of 33 patients with 37 secondary arthrodeses (17 subtalar and 20 triple) with a median follow-up of 116 months were asked to complete questionnaires regarding disease-specific functional outcome (Maryland Foot Score, MFS), quality of life (SF-36) and overall satisfaction with the treatment (Visual Analogue Scale, VAS). Patient groups were comparable considering median age at fracture, initial treatment (conservative or operative), time to arthrodesis, median follow-up, and post-arthrodesis radiographic angles. The MFS score was similar after subtalar versus triple arthrodesis (59 vs. 56 points; P = 0.79). No statistically significant difference was found for the SF-36 (84 vs. 83 points; P = 0.67) and the VAS (5 vs. 6; P = 0.21). Smoking was statistically significantly associated with a non-union (χ2 = 6.60, P = 0.017). The current study suggests that there is no significant difference in functional outcome between an in situ subtalar or triple arthrodesis as a salvage technique for symptomatic arthrosis after an intra-articular calcaneal fracture. Smoking is a risk factor for non-union. PMID:21811905

  20. Evaluation of assumptions in soil moisture triple collocation analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Triple collocation analysis (TCA) enables estimation of error variances for three or more products that retrieve or estimate the same geophysical variable using mutually-independent methods. Several statistical assumptions regarding the statistical nature of errors (e.g., mutual independence and ort...

  1. Triple redundant computer system/display and keyboard subsystem interface

    NASA Technical Reports Server (NTRS)

    Gulde, F. J.

    1973-01-01

    Interfacing of the redundant display and keyboard subsystem with the triple redundant computer system is defined according to space shuttle design. The study is performed in three phases: (1) TRCS configuration and characteristics identification; (2) display and keyboard subsystem configuration and characteristics identification, and (3) interface approach definition.

  2. Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

    ClinicalTrials.gov

    2016-06-30

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  3. Primitive Pythagorean Triples: The 3, 4, 5 Connection

    ERIC Educational Resources Information Center

    Skurnick, Ronald

    2007-01-01

    The Pythagorean Theorem, arguably one of the best-known results in mathematics, states that a triangle is a right triangle if and only if the sum of the squares of the lengths of two of its sides equals the square of the length of its third side. Closely associated with the Pythagorean Theorem is the concept of Pythagorean triples. A "Pythagorean…

  4. Aluminum Silicate System: Experimental Determination of the Triple Point.

    PubMed

    Bell, P M

    1963-03-15

    The kyanite-sillimanite-andalusite triple point exists in the pressure-temperature plane at 8 +/- 0.5 kb and 300 +/- 50 degrees C. Reactions are accomplished experimentally with a Bridgman opposed-anvil press (with an external furnace), modified to provide shearing of the sample charges. All three equilibrium boundaries are proved by reversed reactions. PMID:17812984

  5. Scalable in-memory RDFS closure on billions of triples.

    SciTech Connect

    Goodman, Eric L.; Mizell, David

    2010-06-01

    We present an RDFS closure algorithm, specifically designed and implemented on the Cray XMT supercomputer, that obtains inference rates of 13 million inferences per second on the largest system configuration we used. The Cray XMT, with its large global memory (4TB for our experiments), permits the construction of a conceptually straightforward algorithm, fundamentally a series of operations on a shared hash table. Each thread is given a partition of triple data to process, a dedicated copy of the ontology to apply to the data, and a reference to the hash table into which it inserts inferred triples. The global nature of the hash table allows the algorithm to avoid a common obstacle for distributed memory machines: the creation of duplicate triples. On LUBM data sets ranging between 1.3 billion and 5.3 billion triples, we obtain nearly linear speedup except for two portions: file I/O, which can be ameliorated with the additional service nodes, and data structure initialization, which requires nearly constant time for runs involving 32 processors or more.

  6. The Triple X Chromosome Syndrome in Childhood: Recent Empirical Findings.

    ERIC Educational Resources Information Center

    Rovet, Joanne; Netley, Charles

    1983-01-01

    Examines the performance on verbal, nonverbal, and memory tasks of 11 girls (ages 8 to 11 years) identified as having an extra X chromosome at birth. Results showed that the triple-X girls were markedly inferior in their performance on the tasks, indicating a rehearsal deficit, an inability to use list structures, and weaker language skills.…

  7. Hoogsteen-position pyrimidines promote the stability and function of the MALAT1 RNA triple helix.

    PubMed

    Brown, Jessica A; Kinzig, Charles G; DeGregorio, Suzanne J; Steitz, Joan A

    2016-05-01

    Triple-stranded RNA was first deduced to form in vitro more than 50 years ago and has since been implicated in RNA catalysis, stability, and small molecule binding. Despite the emerging biological significance of RNA triple helices, it remains unclear how their nucleotide composition contributes to their thermodynamic stability and cellular function. To investigate these properties, we used in vitro RNA electrophoretic mobility shift assays (EMSAs) and in vivo intronless β-globin reporter assays to measure the relative contribution of 20 RNA base triples (N•A-U, N•G-C, N•C-G, N•U-A, and N•G-U) to triple-helical stability. These triples replaced a single internal U•A-U within the known structure of the triple-helical RNA stability element of human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which contains 10 major-groove base triples. In addition to the canonical C•G-C triple, the noncanonical base triples U•G-C, U•G-U, C•C-G, and U•C-G exhibited at least 30% stability relative to the wild-type U•A-U base triple in both assays. Of these triples, only U•A-U, C•G-C, and U•G-C, when tested as four successive triples, formed stabilizing structures that allowed accumulation of the intronless β-globin reporter. Overall, we find that Hoogsteen-position pyrimidines support triple helix stability and function and that thermodynamic stability, based on EMSA results, is necessary but not sufficient for stabilization activity of the MALAT1 triple helix in cells. These results suggest that additional RNA triple helices containing noncanonical triples likely exist in nature. PMID:26952103

  8. Is Three a Crowd? Exploring the Development and Satisfaction of Students in Triples

    ERIC Educational Resources Information Center

    Long, Larry D.; Kujawa, Kyle

    2015-01-01

    Tripling, the assignment of a third resident to a room designed for two, is a common practice at many colleges and universities across the United States. Most of the research on tripling was conducted three or four decades ago, and research exploring how living in a triple affects the educational gains and satisfaction of college students is…

  9. Triple Science GCSEs: Strategies for Raising Attainment. GCSEs in Biology, Chemistry and Physics

    ERIC Educational Resources Information Center

    Learning and Skills Network (NJ3), 2007

    2007-01-01

    This publication provides advice for schools exploring the possibility of introducing Triple Science GCSEs. It focuses on strategies for raising attainment generally but within the context of Triple Science. The document is split into six sections: The introduction, titled "Preparing to Implement Triple Science Courses," introduces some of the…

  10. Combinatorics of RNA Secondary Structures with Base Triples.

    PubMed

    Müller, Robert; Nebel, Markus E

    2015-07-01

    The structure of RNA has been the subject of intense research over the last decades due to its importance for the correct functioning of RNA molecules in biological processes. Hence, a large number of models for RNA folding and corresponding algorithms for structure prediction have been developed. However, previous models often only consider base pairs, although every base is capable of up to three edge-to-edge interactions with other bases. Recently, Höner zu Siederdissen et al. presented an extended model of RNA secondary structure, including base triples together with a folding algorithm-the first thermodynamics-based algorithm that allows the prediction of secondary structures with base triples. In this article, we investigate the search space processed by this new algorithm, that is, the combinatorics of extended RNA secondary structures with base triples. We present generalized definitions for structural motifs like hairpins, stems, bulges, or interior loops occurring in structures with base triples. Furthermore, we prove precise asymptotic results for the number of different structures (size of search space) and expectations for various parameters associated with structural motifs (typical shape of folding). Our analysis shows that the asymptotic number of secondary structures of size n increases exponentially to [Formula: see text] compared to the classic model by Stein and Waterman for which [Formula: see text] structures exist. A comparison with the classic model reveals large deviations in the expected structural appearance, too. The inclusion of base triples constitutes a significant refinement of the combinatorial model of RNA secondary structure, which, by our findings, is quantitatively characterized. Our results are of special theoretical interest, because a closer look at the numbers involved suggests that extended RNA secondary structures constitute a new combinatorial class not bijective with any other combinatorial objects studied so far. PMID

  11. Strategic Clinical Networks: Alberta's Response to Triple Aim.

    PubMed

    Noseworthy, Tom; Wasylak, Tracy; O'Neill, Blair J

    2016-01-01

    Verma and Bhatia make a compelling case for the Triple Aim to promote health system innovation and sustainability. We concur. Moreover, the authors offer a useful categorization of policies and actions to advance the Triple Aim under the "classic functions" of financing, stewardship and resource generation (Verma and Bhatia 2016). The argument is tendered that provincial governments should embrace the Triple Aim in the absence of federal government leadership, noting that, by international standards, we are at best mediocre and, more realistically, fighting for the bottom in comparative, annual cross-country surveys. Ignoring federal government participation in Medicare and resorting solely to provincial leadership seems to make sense for the purposes of this discourse; but, it makes no sense at all if we are attempting to achieve high performance in Canada's non-system (Canada Health Action: Building on the Legacy 1997; Commission on the Future of Health Care in Canada 2002; Lewis 2015). As for enlisting provincial governments, we heartily agree. A great deal can be accomplished by the Council of the Federation of Canadian Premiers. But, the entire basis for this philosophy and the reference paper itself assumes a top-down approach to policy and practice. That is what we are trying to change in Alberta and we next discuss. Bottom-up clinically led change, driven by measurement and evidence, has to meet with the top-down approach being presented and widely practiced. While true for each category of financing, stewardship and resource generation, in no place is this truer than what is described and included in "health system stewardship." This commentary draws from Verma and Bhatia (2016) and demonstrates how Alberta, through the use of Strategic Clinical Networks (SCNs), is responding to the Triple Aim. We offer three examples of provincially scaled innovations, each representing one or more arms of the Triple Aim. PMID:27009587

  12. Triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR inhibition (SU5416) in human endothelial and tumor cells

    SciTech Connect

    Bischof, Marc; Abdollahi, Amir; Gong Ping; Stoffregen, Clemens; Lipson, Kenneth E.; Debus, Juergen; Weber, Klaus J.; Huber, Peter E. . E-mail: p.huber@dkfz.de

    2004-11-15

    Purpose: This is the first preclinical report evaluating a trimodal therapy consisting of irradiation, chemotherapy, and antiangiogenesis in the context of a multimodal anticancer strategy. The combination of the folate antimetabolite pemetrexed, SU5416, a receptor tyrosine kinase inhibitor of VEGFR2, and irradiation was investigated in human endothelial cells and tumor cell lines. Methods and materials: Primary isolated human umbilical vein endothelial cells (HUVEC), human dermal microvascular endothelial cells (HDMEC), and human glioblastoma (U87) and prostate cancer cells (PC3) were exposed to pemetrexed (2 h) alone and in combination with SU5416 (2 h). When combined with irradiation up to 8 Gy, fixed concentrations of pemetrexed (1.06 {mu}M) and SU5416 (1.0 {mu}M) were used. Proliferation and clonogenic assays were conducted with endothelial and tumor cells. The migration/invasion ability of endothelial cells and the ability to produce tubular structures were tested in Matrigel and tube formation assays. Apoptosis was measured by sub-G1 DNA and caspase-3 flow cytometry. To investigate underlying cell signaling, immunocytochemistry was used to detect Akt survival signaling involvement. Results: Triple combination using only a low-toxicity drug exposure of pemetrexed and SU5416 results in greater response than each treatment alone or than each combination of two modalities in all tested endothelial and tumor cell models. Triple combination substantially inhibits proliferation, migration/invasion, tube formation, and clonogenic survival. Triple combination also induced the highest rate of apoptosis in HDMEC and HUVEC as indicated by sub-1 G1 and caspase-3 assessment. Interestingly, triple combination therapy also reduces proliferation and clonogenic survival significantly in U87 and PC3 tumor cell lines. SU5416 potently inhibited Akt phosphorylation which could be induced by radiation and radiochemotherapy in human endothelial cells. Conclusions: Our findings

  13. Giant cell tumor of cervicothoracic region treated by triple corpectomy from posterior only approach: A case report with review of literature

    PubMed Central

    Mahajan, Rajat; Chhabra, Harvinder Singh; Tandon, Vikas; Venkatesh, Raghavendra

    2015-01-01

    Giant cell tumor (GCT) is a benign aggressive tumor, which affects axial as well as a peripheral skeleton. It affects epiphysis of long bones and can result in pathological fractures. GCT affects cervical spine rarely and has been known to affect almost all vertebra in the human body. It has a predilection for fixed spine, that is, sacrum though it can affect mobile spine as well. GCT of cervicothoracic region poses a challenge for the surgeon because of the difficulty in approaching this region anteriorly. This situation is further compounded when GCT involves multiple contiguous vertebral bodies in this region and has already spread beyond the confines of its capsule. We report a case of GCT involving three vertebral bodies C7, D1, and D2 at cervicothoracic region who presented to us and was treated with triple corpectomy from the posterior only approach. This is the first ever case report of triple corpectomy and anterior reconstruction by a posterior only approach for GCT at the cervicothoracic junction to the best of author's knowledge. PMID:26692702

  14. Triple negative breast cancer in a poor resource setting in North-Western Tanzania: a preliminary study of 52 patients

    PubMed Central

    2014-01-01

    Background Breast cancer is the second leading cancer worldwide. In Tanzania, though it ranks as the second leading cancer in women after cervical cancer, hormonal receptor status is not carried out routinely in patients. Adjuvant hormonal therapy is given without prior knowledge of hormonal receptors status and patients can incur unnecessary costs and side effects. This study was performed to investigate the expression of hormonal receptors, epidermal growth factor receptors (HER-2) and proliferation index of the breast cancer by Ki-67 in a few selected patients with breast cancer at referral hospital in North-Western Tanzania. The study classified breast cancer subtypes based on hormonal receptors status and the expression of epidermal growth factor receptors. Results A total of 52 cases of breast cancer were investigated. Patients’ mean age at diagnosis was 49 years. The majority of the tumors was invasive ductal carcinoma 47 (90.4%) and 40 (76.9%) were of histological grade III. Thirty-eight (73.1%) of the patient had lymph node metastasis at the time of diagnosis and 36 (69.2%) were at clinical stage III. Only 3 (5.8%) patients were in clinical stage I. There was a tendency of a low level of expression of the receptors, whereby Estrogen Receptor (ER) positive tumors were 17 (32.7%), progesterone receptor (PR) positive tumors were 22 (42.3%), and HER-2 positive tumors were 12 (23.1%). Triple negative tumors constituted 20 (38.4%) of the patients. Most of the tumors (75%) showed high proliferation by Ki-67. Lymph node metastasis was more common in Triple Negative and HER enriched tumors. Conclusion This study showed a tendency for a low level of expression of hormonal receptors. There was a significant proportion of Triple Negative breast cancers. Routine testing for hormonal receptors in breast cancer is recommended before the initiation of adjuvant hormonal therapy. PMID:24964871

  15. One-step fabrication of triple-layered microcapsules by a tri-axial flow focusing device for microencapsulation of soluble drugs and imaging agents

    NASA Astrophysics Data System (ADS)

    Yuan, Shuai; Wu, Qiang; Lei, Fan; Li, Guangbin; Si, Ting; Xu, Ronald X.

    2016-04-01

    In this work, the microencapsulation of water-soluble drug (doxorubicin, Dox) and imaging agent (perfluorocarbon, PFC) is performed by a novel liquid driven tri-axial flow focusing (LDTFF) device. The formation of stable triple-layered cone-jet mode can be observed in the simple well-assembled LDTFF device, providing an easy approach to fabricate mono-disperse triple-layered microcapsules with high encapsulation efficiency, high throughput and low cost in just one step. The fluorescence images show that the microcapsules have a satisfactory core-shell structure. The SEM micrographs show spherical and smooth surface views of the triple-layered microcapsules after being stirred 72h to remove the organic solvent totally. The results of thermo-responsive release experiments of the produced triple-layered microcapsules show these multifunctional capsules can be well stimulated when the environment temperature is beyond 55 degree centigrade. In a word, this novel approach has a great potential in applications such as drug delivery and image-guided therapy.

  16. Combined inhibition of AXL, Lyn and p130Cas kinases block migration of triple negative breast cancer cells

    PubMed Central

    Pénzes, Kinga; Baumann, Christine; Szabadkai, István; Őrfi, László; Kéri, György; Ullrich, Axel; Torka, Robert

    2014-01-01

    Blocking the migration of metastatic cancer cells is a major goal in the therapy of cancer. The receptor tyrosine kinase AXL is one of the main triggers for cancer cell migration in neoplasia of breast, colon, skin, thyroid and prostate. In our study we analyzed the effect of AXL inhibition on cell motility and viability in triple negative breast cancer cell lines overexpressing AXL. Thereby we reveal that the compound BMS777607, exhibiting the lowest IC50 values for inhibition of AXL kinase activity in the studied cell lines, attenuates cell motility to a lower extent than the kinase inhibitors MPCD84111 and SKI606. By analyzing the target kinases of MPCD84111 and SKI606 with kinase profiling assays we identified Lyn, a Src family kinase, as a target of both compounds. Knockdown of Lyn and the migration-related CRK-associated substrate (p130Cas), had a significant inhibitory effect on cell migration. Taken together, our findings highlight the importance of combinatorial or multikinase inhibition of non-receptor tyrosine kinases and AXL receptor tyrosine kinase in the therapy of triple negative breast cancer. PMID:25482942

  17. Zoledronate and Molecular Iodine Cause Synergistic Cell Death in Triple Negative Breast Cancer through Endoplasmic Reticulum Stress.

    PubMed

    Tripathi, Ranu; Singh, Preeti; Singh, Aru; Chagtoo, Megha; Khan, Sajid; Tiwari, Swasti; Agarwal, Gaurav; Meeran, Syed Musthapa; Godbole, Madan M

    2016-01-01

    Women consuming molecular iodine (I2) through seaweeds suffer the least from breast cancers. Zoledronate (Zol) is in clinical use for alleviation of bone pain in cancer patients. Triple negative breast cancers exhibit high mortality due to lack of neoadjuvant chemotherapy. I2 and Zol independently cause weak antiproliferative and apoptotic effect. So far, their combined effects have not been tested. We analyzed the effect of combination of I2 with Zol as a potent adjuvant therapeutic agent for triple negative breast cancer cells (MDA-MBA-231) and in the mice model of breast cancer. Cell viability, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Western blotting, real-time PCR, flow cytometry, and other assays were performed for assessing cell death, calcium levels, and migration potential, respectively, in treated cells. The increased caspase 8, increased [Ca(2+)]c levels, and endoplasmic reticulum (ER) stress resulted in apoptosis. Real time and fluorescence-based analysis demonstrated that the combination treatment targets ER Ca(2+) homeostasis chaperons leading to apoptosis. Combination therapy reduces metalloproteinases 2 and 9, inhibits invasion/migration of cells, and prevents growth of tumor in mice. I2 + Zol combination treatment induces synergistic increase in ER-mediated apoptosis, reduces invasion/migration potential of MDA-MB-231 cells, and exhibits antiproliferative property in vivo demonstrating its potential as combination therapy. PMID:27116040

  18. An ultrasensitive optical label-free polymeric biosensor based on concentric triple microring resonators with a central microdisk resonator

    NASA Astrophysics Data System (ADS)

    Malmir, Kiana; Habibiyan, Hamidreza; Ghafoorifard, Hassan

    2016-04-01

    In this paper we propose an optical label-free biosensor based on a polymeric platform. Label-free biosensors have not the drawbacks and stability problems of commercialized devices which are used for detection of labeled molecules. In addition, we choose polymeric platform, due to simple and low cost fabrication process and also high biocompatibility properties. The suggested structure consists of concentric triple ring resonators along with a disk resonator which offers deeper notches, higher sensitivity and vaster detection area with respect to other similar configurations such as single ring resonator, double concentric ring resonators, etc. Our numerical simulations based on the finite difference time domain (FDTD) method, show that in optimized structure, a transmission notch depth of -48.7 dB for sensor at rest and a free spectral range of 56 nm are achievable. In addition, resonance wavelength sensitivity and output power sensitivity of sensor are 1000 nm/RIU and 1.8×104 dB/RIU, respectively. The external radius of outer ring resonator is only 5 μm, and detection area of the sensor is 40.37 μm2. With this small size, to the best of our knowledge, the obtained notch depth and sensitivity parameters are one of the highest values in ring resonator-based biosensors reported to date.

  19. Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer.

    PubMed

    Chen, Zhong; Lan, Xun; Wu, Dayong; Sunkel, Benjamin; Ye, Zhenqing; Huang, Jiaoti; Liu, Zhihua; Clinton, Steven K; Jin, Victor X; Wang, Qianben

    2015-01-01

    Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC)-regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and are associated with unfavourable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR. PMID:26374485

  20. Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer

    PubMed Central

    Chen, Zhong; Lan, Xun; Wu, Dayong; Sunkel, Benjamin; Ye, Zhenqing; Huang, Jiaoti; Liu, Zhihua; Clinton, Steven K.; Jin, Victor X.; Wang, Qianben

    2015-01-01

    Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC)-regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and are associated with unfavourable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR. PMID:26374485

  1. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer

    PubMed Central

    Collina, Francesca; Di Bonito, Maurizio; Li Bergolis, Valeria; De Laurentiis, Michelino; Vitagliano, Carlo; Cerrone, Margherita; Nuzzo, Francesco; Cantile, Monica; Botti, Gerardo

    2015-01-01

    Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified. PMID:26504780

  2. Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: The Future of Immune Targeting

    PubMed Central

    García-Teijido, Paula; Cabal, María Luque; Fernández, Ignacio Peláez; Pérez, Yolanda Fernández

    2016-01-01

    Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New immune modulatory agents, including immune checkpoints inhibitors, have shown promising activity in a subgroup of metastatic TNBC. Increased programmed cell death protein 1 ligand (PD-L1) expression on the surface of TNBC provides the rationale for implementing therapeutic strategies targeting the PD-1/PD-L1 axis in TNBC. The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, and the PD-L1 inhibitor atezolizumab have shown promising results in clinical trials. PMID:27081325

  3. Highly Adaptable Triple-Negative Breast Cancer Cells as a Functional Model for Testing Anticancer Agents

    PubMed Central

    Singh, Balraj; Shamsnia, Anna; Raythatha, Milan R.; Milligan, Ryan D.; Cady, Amanda M.; Madan, Simran; Lucci, Anthony

    2014-01-01

    A major obstacle in developing effective therapies against solid tumors stems from an inability to adequately model the rare subpopulation of panresistant cancer cells that may often drive the disease. We describe a strategy for optimally modeling highly abnormal and highly adaptable human triple-negative breast cancer cells, and evaluating therapies for their ability to eradicate such cells. To overcome the shortcomings often associated with cell culture models, we incorporated several features in our model including a selection of highly adaptable cancer cells based on their ability to survive a metabolic challenge. We have previously shown that metabolically adaptable cancer cells efficiently metastasize to multiple organs in nude mice. Here we show that the cancer cells modeled in our system feature an embryo-like gene expression and amplification of the fat mass and obesity associated gene FTO. We also provide evidence of upregulation of ZEB1 and downregulation of GRHL2 indicating increased epithelial to mesenchymal transition in metabolically adaptable cancer cells. Our results obtained with a variety of anticancer agents support the validity of the model of realistic panresistance and suggest that it could be used for developing anticancer agents that would overcome panresistance. PMID:25279830

  4. Tumor suppressor role of microRNA-1296 in triple-negative breast cancer

    PubMed Central

    Phan, Binh; Majid, Shahana; Ursu, Sarah; de Semir, David; Nosrati, Mehdi; Bezrookove, Vladimir; Kashani-Sabet, Mohammed; Dar, Altaf A.

    2016-01-01

    Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis, which lacks effective targeted therapies. There is an urgent need to better understand the underlying molecular mechanisms of TNBC aggressiveness and identify novel, efficient targets for therapeutic intervention. Methods miRNA qRT-PCR was used to determine the expression of miR-1296 in cell lines. The miR-1296 overexpression effects in TNBC cell lines were investigated using assays of colony formation, cell cycle and apoptosis. Immunoblotting was performed to determine the expression of the miR-1296 target protein, and luciferase assays were performed to confirm the target of miR-1296 action. Results miR-1296 expression was significantly suppressed in TNBC cell lines and tissues samples. Overexpression of miR-1296 significantly suppressed cell proliferation of two TNBC cell lines when compared to control miRNA-expressing cells. A significant decrease in the S-phase of the cell cycle was observed following miR-1296 overexpression, accompanied by induction of apoptosis in TNBC cells. Cyclin D1 (CCND1) was identified as a target of miR-1296 action. miR-1296 overexpression significantly suppressed the luciferase activity of reporter plasmid containing the 3′UTR of CCND1 and protein expression levels of CCND1 in TNBC cells. The effects of miR-1296 overexpression on TNBC cell growth were reversed by CCND1 overexpression. miR-1296 expression sensitized TNBC cells to cisplatin treatment. Conclusion Our results demonstrate a novel tumor suppressor role for miR-1296 in triple-negative breast cancer cell lines, identify CCND1 as its target of action, and demonstrate a potential role for miR-1296 in sensitizing breast cancer cells to cisplatin. PMID:26799586

  5. Chloroquine has tumor-inhibitory and tumor-promoting effects in triple-negative breast cancer

    PubMed Central

    TUOMELA, JOHANNA; SANDHOLM, JOUKO; KAUPPILA, JOONAS H.; LEHENKARI, PETRI; HARRIS, KEVIN W.; SELANDER, KATRI S.

    2013-01-01

    Toll-like receptor-9 (TLR9) is an intracellular DNA receptor that is widely expressed in breast and other cancers. We previously demonstrated that low tumor TLR9 expression upon diagnosis is associated with significantly shortened disease-specific survival times in patients with triple-negative breast cancer (TNBC). There are no targeted therapies for this subgroup of patients whose prognosis is among the worst in breast cancer. Due to the previously detected in vitro anti-invasive effects of chloroquine in these cell lines, the present study aimed to investigate the in vivo effects of chloroquine against two clinical subtypes of TNBC that differ in TLR9 expression. Chloroquine suppressed matrix metalloproteinase (MMP)-2 and MMP-9 mRNA expression and protein activity, whereas MMP-13 mRNA expression and proteolytic activity were increased. Despite enhancing TLR9 mRNA expression, chloroquine suppressed TLR9 protein expression in vitro. Daily treatment of mice with intraperitoneal (i.p.) chloroquine (80 mg/kg/day) for 22 days, did not inhibit the growth of control siRNA or TLR9 siRNA MDA-MB-231 breast cancer cells. In conclusion, despite the favorable in vitro effects on TNBC invasion and viability, particularly in hypoxic conditions, chloroquine does not prevent the growth of the triple-negative MDA-MB-231 cells with high or low TLR9 expression levels in vivo. This may be explained by the activating effects of chloroquine on MMP-13 expression or by the fact that chloroquine, by suppressing TLR9 expression, permits the activation of currently unknown molecular pathways, which allow the aggressive behavior of TNBC cells with low TLR9 expression in hypoxia. PMID:24273604

  6. Targeting triple-negative breast cancer cells with 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles.

    PubMed

    Santos, Kathleen; Laranjo, Mafalda; Abrantes, Ana Margarida; Brito, Ana F; Gonçalves, Cristina; Sarmento Ribeiro, Ana Bela; Botelho, M Filomena; Soares, Maria I L; Oliveira, Andreia S R; Pinho e Melo, Teresa M V D

    2014-05-22

    Further studies on 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles as anticancer agents against breast cancer are reported, allowing to demonstrate the potential of these compounds for the therapy of the triple-negative breast cancer, the most challenging tumors in clinical practice. These compounds were assayed for their in vitro cytotoxicity on several human breast cancer cell lines (MCF7, HCC1954 and HCC1806 cell lines). Particularly interesting were the results obtained for 4-hydroxyphenyl substituted derivative, which proved to be the most promising compound regarding HCC1806 cell line, a triple-negative breast cancer. The effects of the two most active compounds on cell survival, viability, cell cycle, DNA damage and expression of proteins related to cell death pathways were studied. The reported results consolidate the potential of 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles for the therapy of breast cancer, particularly the triple-negative. PMID:24747064

  7. Metastable polymorphs of hydrogen isotopes solidified near the triple point

    NASA Astrophysics Data System (ADS)

    Kozioziemski, B. J.; Chernov, A. A.; Mapoles, E. R.; Sater, J. D.

    2010-07-01

    Hydrogen (H2) , deuterium (D2) , and the 0.25D2-0.5DT-0.25T2 isotopic mixture of deuterium and tritium (D-T) each form a metastable solid state below their respective triple-point temperatures (TTP) . The metastable solid is observed to nucleate and grow from inside of a 5-10μm inner diameter borosilicate glass tube when the liquid hydrogens are slowly cooled through their respective TTP . These metastable solids have their triple-point temperature 15-43 mK below the stable hexagonal close-packed (hcp) crystal of the same composition, a different growth habit, and recrystallize to the hcp solid. This metastable solid may be a crystal with unknown structure or, less likely, hcp with stacking faults and other defects.

  8. Kondo Effect in a Triple Quantum-Dot Array

    NASA Astrophysics Data System (ADS)

    Oguri, Akira; Nisikawa, Yunori; Hewson, A. C.

    2006-09-01

    We study the ground-state properties of a triple quantum dot based on a three-site Hubbard model connected to two non-interacting leads. Using the numerical renormalization group (NRG), the many-body phase shifts and dc conductance are calculated away from half-filling as a function of the onsite energy ɛd, which corresponds to the gate voltage. The results for conductance g show the typical Kondo plateaus of the Unitary limit g ≈ 2e2/h at some finite ranges of the gate-voltage corresponding to odd Nel (≈ 1, 3 and 5), where Nel is the total number of electrons in the triple dot. The conductance shows broad minima for even Nel(≈ 2 and 4). The local charge Nel shows a staircase behavior as a function of ɛd.

  9. A compact triple-band bandpass filter based on metamaterials

    NASA Astrophysics Data System (ADS)

    Zhao, Ya-juan; Jiang, Bo; Li, Bao-yi; Wang, Dong-hong

    2016-07-01

    This paper presents a compact triple-band bandpass filter based on metamaterials. The miniaturization is realized by the principle of phase compensation of metamaterial. Compared with the conventional half-wavelength filter, the metamaterial filter has a small size of 10 mm×10 mm. The triple-band bandpass filter performance has been validated by the electromagnetic simulation software of high frequency structure simulator (HFSS). The results illustrate that the filter is designed with center frequencies of 2.4 GHz, 5.1 GHz and 8.8 GHz, bandwidths of about 7.9% (2.31—2.50 GHz), 7.8% (5.0—5.4 GHz) and 7.4% (8.50—9.15 GHz), respectively, and it shows good band pass characteristics.

  10. Dynamical Evolution of the Alpha and Proxima Centauri Triple System

    NASA Astrophysics Data System (ADS)

    Worth, Rachel; Sigurdsson, Steinn

    2015-01-01

    Proxima Centauri is approximately 15,000 AU from the Alpha Centauri binary and moving through the galaxy on a similar path, and is thought to be in a loosely bound orbit about the binary. Dynamic simulations show that this configuration can form from a less extreme triple system. As our nearest neighbors, these stars command great interest as potential planet hosts, and the dynamics of the stars govern the formation of any planets within the system. Here we present a scenario for the evolution of Alpha Centauri A and B and Proxima Centauri as a triple system, to establish limits on the evolution of the binary since formation and allow for a better understanding of planet formation therein.

  11. Triple neutral gauge boson couplings in noncommutative Standard Model

    NASA Astrophysics Data System (ADS)

    Deshpande, N. G.; He, Xiao-Gang

    2002-05-01

    It has been shown recently that the triple neutral gauge boson couplings are not uniquely determined in noncommutative extension of the Standard Model (NCSM). Depending on specific schemes used, the couplings are different and may even be zero. To distinguish different realizations of the NCSM, additional information either from theoretical or experimental considerations is needed. In this Letter we show that these couplings can be uniquely determined from considerations of unification of electroweak and strong interactions. Using SU(5) as the underlying theory and integrating out the heavy degrees of freedom, we obtain unique non-zero new triple γγγ, γγZ, γZZ, ZZZ, γGG, ZGG and GGG couplings at the leading order in the NCSM. We also briefly discuss experimental implications.

  12. [Triple Descemet membrane endothelial keratoplasty : Indications, variations and results].

    PubMed

    Girbardt, C; Wiedemann, P; Nestler, A

    2016-03-01

    When Descemet membrane endothelial keratoplasty (DMEK) is indicated in patients with phakic eyes, a combination with phacoemulsification and intraocular lens implantation in one sitting should be considered as a triple DMEK. The best possible preoperative deswelling of the cornea should be strived for in order to allow sufficient viewing conditions for the individual stages of cataract surgery. Furthermore, technical details, e.g. regulation of pupillary width also must be considered. The power of the intraocular lens has to be adjusted in order to compensate for the shift of refraction towards hyperopic values induced by DMEK surgery. A rapid and clear improvement in visual acuity can normally be achieved after a triple DMEK. There seem to be no disadvantages compared with a two-stage procedure for DMEK and cataract surgery. PMID:26857142

  13. Photodissociation of methyl formate: Conical intersections, roaming and triple fragmentation

    NASA Astrophysics Data System (ADS)

    Lin, King-Chuen; Tsai, Po-Yu; Chao, Meng-Hsuan; Kasai, Toshio; Lombardi, Andrea; Palazzetti, Federico; Aquilanti, Vincenzo

    2015-12-01

    The photodissociation channels of methyl formate have been extensively investigated by two different advanced experimental techniques, ion imaging and Fourier-Transform-Infrared emission spectroscopy, combined with quantum chemical calculations and molecular dynamics simulations. Our aim is to characterize the role of alternative routes to the conventional transition-state mediated pathway: the roaming and the triple fragmentation processes. The photolysis experiments, carried out at a range of laser wavelengths in the vicinity of the triple fragmentation threshold, beside the simulation of large bunches of classical trajectories with different initial conditions, have shown that both mechanisms share a common path that involves a conical intersection during the relaxation process from the electronic excited state S1 to the ground state S0.

  14. Simulation of Triple Oxidation Ditch Wastewater Treatment Process

    NASA Astrophysics Data System (ADS)

    Yang, Yue; Zhang, Jinsong; Liu, Lixiang; Hu, Yongfeng; Xu, Ziming

    2010-11-01

    This paper presented the modeling mechanism and method of a sewage treatment system. A triple oxidation ditch process of a WWTP was simulated based on activated sludge model ASM2D with GPS-X software. In order to identify the adequate model structure to be implemented into the GPS-X environment, the oxidation ditch was divided into several completely stirred tank reactors depended on the distribution of aeration devices and dissolved oxygen concentration. The removal efficiency of COD, ammonia nitrogen, total nitrogen, total phosphorus and SS were simulated by GPS-X software with influent quality data of this WWTP from June to August 2009, to investigate the differences between the simulated results and the actual results. The results showed that, the simulated values could well reflect the actual condition of the triple oxidation ditch process. Mathematical modeling method was appropriate in effluent quality predicting and process optimizing.

  15. Grain boundary and triple junction diffusion in nanocrystalline copper

    SciTech Connect

    Wegner, M. Leuthold, J.; Peterlechner, M.; Divinski, S. V.; Song, X.; Wilde, G.

    2014-09-07

    Grain boundary and triple junction diffusion in nanocrystalline Cu samples with grain sizes, 〈d〉, of ∼35 and ∼44 nm produced by spark plasma sintering were investigated by the radiotracer method using the {sup 63}Ni isotope. The measured diffusivities, D{sub eff}, are comparable with those determined previously for Ni grain boundary diffusion in well-annealed, high purity, coarse grained, polycrystalline copper, substantiating the absence of a grain size effect on the kinetic properties of grain boundaries in a nanocrystalline material at grain sizes d ≥ 35 nm. Simultaneously, the analysis predicts that if triple junction diffusion of Ni in Cu is enhanced with respect to the corresponding grain boundary diffusion rate, it is still less than 500⋅D{sub gb} within the temperature interval from 420 K to 470 K.

  16. Extreme AO Observations of Two Triple Asteroid Systems with SPHERE

    NASA Astrophysics Data System (ADS)

    Yang, B.; Wahhaj, Z.; Beauvalet, L.; Marchis, F.; Dumas, C.; Marsset, M.; Nielsen, E. L.; Vachier, F.

    2016-04-01

    We present the discovery of a new satellite of asteroid (130) Elektra—S/2014 (130) 1—in differential imaging and in integral field spectroscopy data over multiple epochs obtained with Spectro-Polarimetric High-contrast Exoplanet Research/Very Large Telescope. This new (second) moonlet of Elektra is about 2 km across, on an eccentric orbit, and about 500 km away from the primary. For a comparative study, we also observed another triple asteroid system, (93) Minerva. For both systems, component-resolved reflectance spectra of the satellites and primary were obtained simultaneously. No significant spectral difference was observed between the satellites and the primary for either triple system. We find that the moonlets in both systems are more likely to have been created by sub-disruptive impacts as opposed to having been captured.

  17. Triple dividends of water consumption charges in South Africa

    NASA Astrophysics Data System (ADS)

    Letsoalo, Anthony; Blignaut, James; de Wet, Theuns; de Wit, Martin; Hess, Sebastiaan; Tol, Richard S. J.; van Heerden, Jan

    2007-05-01

    The South African government is exploring ways to address water scarcity problems by introducing a water resource management charge on the quantity of water used in sectors such as irrigated agriculture, mining, and forestry. It is expected that a more efficient water allocation, lower use, and a positive impact on poverty can be achieved. This paper reports on the validity of these claims by applying a computable general equilibrium model to analyze the triple dividend of water consumption charges in South Africa: reduced water use, more rapid economic growth, and a more equal income distribution. It is shown that an appropriate budget-neutral combination of water charges, particularly on irrigated agriculture and coal mining, and reduced indirect taxes, particularly on food, would yield triple dividends, that is, less water use, more growth, and less poverty.

  18. Treatment options for patients with triple-negative breast cancer

    PubMed Central

    2010-01-01

    Breast cancer is a heterogeneous disease composed of different subtypes, characterized by their different clinicopathological characteristics, prognoses and responses to treatment. In the past decade, significant advances have been made in the treatment of breast cancer sensitive to hormonal treatments, as well as in patients whose malignant cells overexpress or amplify HER2. In contrast, mainly due to the lack of molecular targets, little progress has been made in the treatment of patients with triple-negative breast cancer. Recent improved understanding of the natural history, pathophysiology, and molecular features of triple-negative breast cancers have provided new insights into management and therapeutic strategies for women affected with this entity. Ongoing and planned translational clinical trials are likely to optimize and improve treatment of women with this disease. PMID:20979652

  19. Entanglement switching via the Kondo effect in triple quantum dots

    NASA Astrophysics Data System (ADS)

    Tooski, S. B.; Bułka, Bogdan R.; Žitko, Rok; Ramšak, Anton

    2014-06-01

    We consider a triple quantum dot system in a triangular geometry with one of the dots connected to metallic leads. Using Wilson's numerical renormalization group method, we investigate quantum entanglement and its relation to the thermodynamic and transport properties in the regime where each of the dots is singly occupied on average, but with non-negligible charge fluctuations. It is shown that even in the regime of significant charge fluctuations the formation of the Kondo singlets induces switching between separable and perfectly entangled states. The quantum phase transition between unentangled and entangled states is analyzed quantitatively and the corresponding phase diagram is explained by exactly solvable spin model. In the framework of an effective model we also explain smearing of the entanglement transition for cases when the symmetry of the triple quantum dot system is relaxed.

  20. Theory of anomalous magnetotransport in triple quantum dots

    NASA Astrophysics Data System (ADS)

    D'Anjou, Benjamin; Coish, William A.

    2012-02-01

    Magneto-transport measurements on a triple quantum dot ring have recently shown anomalous quantum oscillations with dominant frequencies separated by a factor of three in magnetic flux [1]. Such oscillations, suggestive of a one-third periodicity in the flux quantum, are usually not observed in larger mesoscopic rings in which only larger periods are observed. We develop a microscopic transport model for the triple dot and show that the anomalous oscillations can dominate the transport behavior under certain conditions. Furthermore, we discuss the range of validity of our model by studying dephasing due to broadening and electric dipole interactions. [4pt] [1] L. Gaudreau et al., Phys. Rev. B 80, 075415 (2009)

  1. Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel-cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines.

    PubMed

    Ye, Jun; Xia, Xuejun; Dong, Wujun; Hao, Huazhen; Meng, Luhua; Yang, Yanfang; Wang, Renyun; Lyu, Yuanfeng; Liu, Yuling

    2016-01-01

    There is no effective clinical therapy for triple-negative breast cancers (TNBCs), which have high low-density lipoprotein (LDL) requirements and express relatively high levels of LDL receptors (LDLRs) on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel-cholesterol complex (PTX-CH Emul) was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231) and non-TNBC (MCF7) cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native LDL. The findings of this paper further confirm the therapeutic potential of PTX-CH Emul in clinical applications involving TNBC therapy. PMID:27601899

  2. Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

    PubMed Central

    Ye, Jun; Xia, Xuejun; Dong, Wujun; Hao, Huazhen; Meng, Luhua; Yang, Yanfang; Wang, Renyun; Lyu, Yuanfeng; Liu, Yuling

    2016-01-01

    There is no effective clinical therapy for triple-negative breast cancers (TNBCs), which have high low-density lipoprotein (LDL) requirements and express relatively high levels of LDL receptors (LDLRs) on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel–cholesterol complex (PTX-CH Emul) was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231) and non-TNBC (MCF7) cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native LDL. The findings of this paper further confirm the therapeutic potential of PTX-CH Emul in clinical applications involving TNBC therapy. PMID:27601899

  3. Dietary intake measurement using 7 d diet diaries in British men and women in the European Prospective Investigation into Cancer-Norfolk study: a focus on methodological issues.

    PubMed

    Lentjes, Marleen A H; McTaggart, Alison; Mulligan, Angela A; Powell, Natasha A; Parry-Smith, David; Luben, Robert N; Bhaniani, Amit; Welch, Ailsa A; Khaw, Kay-Tee

    2014-02-01

    The aim of the present study was to describe the energy, nutrient and crude v. disaggregated food intake measured using 7 d diet diaries (7dDD) for the full baseline Norfolk cohort recruited for the European Prospective Investigation into Cancer (EPIC-Norfolk) study, with emphasis on methodological issues. The first data collection took place between 1993 and 1998 in Norfolk, East Anglia (UK). Of the 30,445 men and women, aged 40-79 years, registered with a general practitioner invited to participate in the study, 25,639 came for a health examination and were asked to complete a 7dDD. Data from diaries with data recorded for at least 1 d were obtained for 99% members of the cohort; 10,354 (89·8%) of the men and 12,779 (91·5%) of the women completed the diet diaries for all 7 d. Mean energy intake (EI) was 9·44 (SD 2·22) MJ/d and 7·15 (SD 1·66) MJ/d, respectively. EI remained approximately stable across the days, but there was apparent under-reporting among the participants, especially among those with BMI >25 kg/m². Micronutrient density was higher among women than among men. In conclusion, under-reporting is an issue, but not more so than that found in national surveys. How foods were grouped (crude or disaggregated) made a difference to the estimates obtained, and comparison of intakes showed wide limits of agreement. The choice of variables influences estimates obtained from the food group data; while this may not alter the ranking of individuals within studies, this issue may be relevant when comparing absolute food intakes between studies. PMID:24041116

  4. Tulczyjew triples in the constrained dynamics of strings

    NASA Astrophysics Data System (ADS)

    Grabowski, J.; Grabowska, K.; Urbański, P.

    2016-09-01

    We show that there exists a natural Tulczyjew triple in the dynamics of objects for which the standard (kinematic) configuration space TM is replaced with ∧n TM . In this framework, which is completely covariant, we derive geometrically phase equations, as well as Euler-Lagrange equations, including nonholonomic constraints into the picture. Dynamics of strings and a constrained Plateau problem in statics are particular cases of this framework.

  5. View north towards yard Triple Stub Switch in foreground. The ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View north towards yard Triple Stub Switch in foreground. The three tracks lead into the East Railroad's Shop complex and Roundhouse. The Steel Hopper Car was used to haul coal and was in the process of being rebuilt but in 1956, when the railroad ended freight operations. As a result it was never completed and was left outside - East Broad Top Railroad & Coal Company, State Route 994, West of U.S. Route 522, Rockhill Furnace, Huntingdon County, PA

  6. Light pressure acceleration with frequency-tripled laser pulse

    SciTech Connect

    Wang, Xiaofeng; Shen, Baifei E-mail: zhxm@siom.ac.cn; Zhang, Xiaomei E-mail: zhxm@siom.ac.cn; Ji, Liangliang; Wang, Wenpeng; Zhao, Xueyan; Xu, Jiancai; Yu, Yahong; Yi, Longqing; Shi, Yin; Xu, Tongjun; Zhang, Lingang

    2014-08-15

    Light pressure acceleration of ions in the interaction of the frequency-tripled (3ω) laser pulse and foil target is studied, and a promising method to increase accelerated ion energy is shown. Results show that at a constant laser energy, much higher ion energy peak value is obtained for 3ω laser compared with that using the fundamental frequency laser. The effect of energy loss during frequency conversion on ion acceleration is considered, which may slightly decrease the acceleration effect.

  7. Study of Neutral Triple Gauge Couplings in DELPHI

    NASA Astrophysics Data System (ADS)

    Pieri, Lidia

    2002-04-01

    Neutral Triple Gauge boson Couplings ZZZ, ZZ γ and Z γ γ are studied using data collected by the DELPHI detector at LEP at energies between 189 and 208 GeV. The reactions e^+ e^- arrow Z γ, e^+ e^- arrow Z Z and e^+ e^- arrow Z γ^* are used. A summary of the main theoretical aspects of NTGC is given. A summary of the reactions used for deriving limits on these couplings is reported. Current limits are shown.

  8. Characteristics of Known Triple Asteroid Systems in the Main Belt

    NASA Astrophysics Data System (ADS)

    Marchis, Franck; Berthier, J.; Burns, K. J.; Descamps, P.; Durech, J.; Emery, J. P.; Enriquez, J. E.; Lainey, V.; Reiss, A. E.; Vachier, F.

    2010-10-01

    Since the discovery of "Sylvia Remus II” [1], around the binary asteroid (87) Sylvia [2] using the VLT/NACO instrument, the number of known triple systems increased significantly. Using the same instrument, a second moonlet was discovered around the binary (45) Eugenia [3] in 2007 [4]. Using an improved W.M. Keck II AO system, [5] announced the discovery of two 3 & 5-km moons orbiting the M-type asteroid (216) Kleopatra and more recently, [6] revealed the presence of two tiny 4-km moons around the C-type (93) Minerva. 3749 Balam is a different triple asteroid system whose existence was suggested by combining lightcurves and AO observations [7]. The properties of these triple systems have been derived individually and published recently [1, 8,9,10]. We will review and contrast their characteristics, including the orbital parameters of the satellite orbits, the size and shape of the primary and the satellites, their taxonomic classes, their bulk densities, and their ages. The goal of this study is to uncover clues concerning the formation and evolution of these mini-planetary systems. The National Science Foundation supported this research under award number AAG-0807468. 1. Marchis et al. Nature 2005 2. Brown et al., IAU 7588, 2001 3. Merline et al. Nature 401, 1999 4. Marchis et al. IAU 1073, 2007 5. Marchis et al. IAU 8980, 2008 6. Marchis et al., IAU 9069, 2009 7. Marchis et al., IAU 8928, 2008 8. Marchis et al., A Dynamical Solution of the Triple Asteroid System (45) Eugenia , Icarus in press, 2010 9. Descamps et al, Triplicity and Physical Characteristics of Asteroid 216 Kleopatra Icarus, in revision, 2010 10. Marchis et al., Triplicity and Physical Characteristics of the main-belt Asteroid (93) Minerva, Icarus submitted 2010

  9. K(pin)-Torsors and the Interpretation of "Triple" Cohomology.

    PubMed

    Duskin, J

    1974-06-01

    A categorical, semi-simplicial interpretation theory for "triple" cohomology is outlined which uses the groups TORS(U) (n)[X;pi] of connected components of certain categories of K(pi,n)-torsors (higher dimensional generalizations of locally trivial principal fiber bundles) to interpret the cohomology groups, i.e., TORS(U) (n)[X;pi] [unk] H(n)(X;pi), n >/= 1. PMID:16592164

  10. Targeting Thyroid Hormone Receptor Beta in Triple Negative Breast Cancer

    PubMed Central

    Gu, Guowei; Gelsomino, Luca; Covington, Kyle R.; Beyer, Amanda R.; Wang, John; Rechoum, Yassine; Huffman, Kenneth; Carstens, Ryan; Ando, Sebastiano; Fuqua, Suzanne A.W.

    2015-01-01

    Purpose Discover novel nuclear receptor targets in triple negative breast cancer Methods Expression microarray, western blot, qRT-PCR, MTT growth assay, soft agar anchorage-independent growth assay, TRE reporter transactivation assay, statistical analysis. Results We performed microarray analysis using 227 triple negative breast tumors, and clustered the tumors into five groups according to their nuclear receptor expression. Thyroid hormone receptor beta (TRβ) was one of the most differentially expressed nuclear receptors in group 5 compared to other groups. TRβ low expressing patients were associated with poor outcome. We evaluated the role of TRβ in triple negative breast cancer cell lines representing group 5 tumors. Knockdown of TRβ increased soft agar colony and reduced sensitivity to docetaxel and doxorubicin treatment. Docetaxel or doxorubicin long-term cultured cell lines also expressed decreased TRβ protein. Microarray analysis revealed cAMP/PKA signaling was the only KEGG pathways upregulated in TRβ knockdown cells. Inhibitors of cAMP or PKA, in combination with doxorubicin further enhanced cell apoptosis and restored sensitivity to chemotherapy. TRβ-specific agonists enhanced TRβ expression, and further sensitized cells to both docetaxel and doxorubicin. Sensitization was mediated by increased apoptosis with elevated cleaved PARP and caspase 3. Conclusions TRβ represents a novel nuclear receptor target in triple negative breast cancer; low TRβ levels were associated with enhanced resistance to both docetaxel and doxorubicin treatment. TRβ-specific agonists enhance chemosensitivity to these two agents. Mechanistically enhanced cAMP/PKA signaling was associated with TRβ’s effects on response to chemotherapy. PMID:25820519

  11. Triple AIM evaluation and application in advanced node

    NASA Astrophysics Data System (ADS)

    Wang, Gary C.; Lio, En Chuan; Hung, Yuting; Chen, Charlie; Wang, Sybil; Weng, Tang Chun; Lin, Bill; Yu, Chun Chi

    2016-03-01

    A novel method on advanced node for IBO (Image Based Overlay) data extraction accuracy is demonstrated in this work, and here some special design in triple-AIM (Advanced Imaging Metrology) is able to realize the approach. Since triple AIM design has 3 locations left for patterning layers insertion, a new design with 2 layers locations, location-A (inner) and location-B (middle), are generated by 1st pattering, i.e. once lithography exposure, and the 2 marks grouping are formed on dielectric through lithography and etching process with a predetermined overlay "zero offset" through original mask layout design, as illustrated in Fig. (1). And then, as following top photo resist layer, assumed location-C (outer), lithography patterning process, PR coating, exposure and development complete, full triple-AIM patterns is generated, and 3 sets of overlay data could be obtained, A to B, C to B, C to A. Through re-calculating the overlay raw data of current (2nd patterning layer) to previous (1st patterning layer) layer by averaging [C to B] and [C to A], then theoretically the data extraction of sites would be more accuracy, since the variation of local marks signal, induced by inline process instability, could be minimized through the raw data averaging procedure. Moreover, from raw data [A to B], an extra monitor function for detections of the inline process variation, marks selection and recipe setting optimization could be obtained, since marks in [A] and [BB] locations are both generated in 1st patterning, and with the target "zero". So if the raw data [A to BB] is bigger or smaller than "zero" in some degree, there should be some process issue or marks condition setting error in triple-AIM design.

  12. UNIDENTIFIED CATENARY SUSPENSION BRIDGE WITH TRIPLE PIPE TOWERS, SHOWING HOWE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    UNIDENTIFIED CATENARY SUSPENSION BRIDGE WITH TRIPLE PIPE TOWERS, SHOWING HOWE PIPE TRUSS RAILING AND TRUSSED DECK BEAMS TYPICAL TO BRIDGES BUILT BY FLINN-MOYER COMPANY. NOTE THAT TOWER PIPES LIE IN ONE PLANE, UNLIKE TRIPODAL ARRANGEMENT AT CLEAR FORK OF THE BRAZOS SUSPENSION BRIDGE. ELEVATION VIEW. - Clear Fork of Brazos River Suspension Bridge, Spanning Clear Fork of Brazos River at County Route 179, Albany, Shackelford County, TX

  13. TripleRank: Ranking Semantic Web Data by Tensor Decomposition

    NASA Astrophysics Data System (ADS)

    Franz, Thomas; Schultz, Antje; Sizov, Sergej; Staab, Steffen

    The Semantic Web fosters novel applications targeting a more efficient and satisfying exploitation of the data available on the web, e.g. faceted browsing of linked open data. Large amounts and high diversity of knowledge in the Semantic Web pose the challenging question of appropriate relevance ranking for producing fine-grained and rich descriptions of the available data, e.g. to guide the user along most promising knowledge aspects. Existing methods for graph-based authority ranking lack support for fine-grained latent coherence between resources and predicates (i.e. support for link semantics in the linked data model). In this paper, we present TripleRank, a novel approach for faceted authority ranking in the context of RDF knowledge bases. TripleRank captures the additional latent semantics of Semantic Web data by means of statistical methods in order to produce richer descriptions of the available data. We model the Semantic Web by a 3-dimensional tensor that enables the seamless representation of arbitrary semantic links. For the analysis of that model, we apply the PARAFAC decomposition, which can be seen as a multi-modal counterpart to Web authority ranking with HITS. The result are groupings of resources and predicates that characterize their authority and navigational (hub) properties with respect to identified topics. We have applied TripleRank to multiple data sets from the linked open data community and gathered encouraging feedback in a user evaluation where TripleRank results have been exploited in a faceted browsing scenario.

  14. miRNA Expression Profile and Involvement of Let-7d-APP in Aged Rats with Isoflurane-Induced Learning and Memory Impairment

    PubMed Central

    Shi, Rong; Xu, Chengshi; Wang, Yun; Cai, Jun; Yue, Yun; Wu, Anshi

    2015-01-01

    MicroRNAs (miRNAs) play a key role in different nervous system diseases. We sought to determine the role of miRNAs in isoflurane-induced learning and memory impairment in aged rats. Male Sprague-Dawley (SD) rats of 18 month were randomly assigned to control group (exposed to mock anesthesia), 2-hour group and 6-hour group (exposed to 2% isoflurane for 2 and 6 hours respectively). By Morris Water Maze, 6-hour group showed impaired learning and memory ability while 2-hour group not. As shown by miRNA array, control group and 2-hour group showed a similar miRNA expression profile. And 38 miRNAs are differently expressed in 6-hour group compared to the other 2 groups, including 21 up-regulated miRNAs and 17 down-regulated miRNAs. And 4 of the differentially expressed miRNAs were validated independently by qRT-PCR. Let-7d was downregulated in 6-hour group. Additionally, we demonstrated that amyloid precursor protein (APP) was a direct target of let-7d by Fluorescent report assay. Increased expression of APP and amyloid-β (Aβ) were found in the hippocampi of 6-hour group. Downregulation of let-7d might contribute to isoflurane-induced learning and memory impairment through upregulating its target APP, and increasing the production of Aβ subsequently. PMID:25799420

  15. Photo-active collagen systems with controlled triple helix architecture

    PubMed Central

    Tronci, Giuseppe; Russell, Stephen J.; Wood, David J.

    2016-01-01

    The design of photo-active collagen systems is presented as a basis for establishing biomimetic materials with varied network architecture and programmable macroscopic properties. Following in-house isolation of type I collagen, reaction with vinyl-bearing compounds of varied backbone rigidity, i.e. 4-vinylbenzyl chloride (4VBC) and glycidyl methacrylate (GMA), was carried out. TNBS colorimetric assay, 1H-NMR and ATR-FTIR confirmed covalent and tunable functionalization of collagen lysines. Depending on the type and extent of functionalization, controlled stability and thermal denaturation of triple helices were observed via circular dichroism (CD), whereby the hydrogen-bonding capability of introduced moieties was shown to play a major role. Full gel formation was observed following photo-activation of functionalized collagen solutions. The presence of a covalent network only slightly affected collagen triple helix conformation (as observed by WAXS and ATR-FTIR), confirming the structural organization of functionalized collagen precursors. Photo-activated hydrogels demonstrated an increased denaturation temperature (DSC) with respect to native collagen, suggesting that the formation of the covalent network successfully stabilized collagen triple helices. Moreover, biocompatibility and mechanical competence of obtained hydrogels were successfully demonstrated under physiologically-relevant conditions. These results demonstrate that this novel synthetic approach enabled the formation of biocompatible collagen systems with defined network architecture and programmable macroscopic properties, which can only partially be obtained with current synthetic methods.

  16. Coupled-Cluster Dynamic Polarizabilities Including Triple Excitations

    SciTech Connect

    Hammond, Jeffrey R.; De Jong, Wibe A.; Kowalski, Karol

    2008-06-10

    Dynamic polarizabilities for open- and closed-shell molecules were obtained using coupled-cluster (CC) linear response theory with full treatment of singles, doubles and triples (CCSDT-LR) with large basis sets utilizing the NWChem software suite. Using four approximate CC methods in conjunction with augmented cc-pVNZ basis sets, we are able to evaluate the convergence in both many-electron and one-electron spaces. For systems with primarily dynamic correlation, the results for CC3 and CCSDT are almost indistinguishable. For systems with more static correlation, the PS(T) approximation [J. Chem. Phs. 127, 164105 (2007) performs better that CC3. Additionally, the PS(T) approach separates the triples contribution to the poles of the response function from the triples amplitudes themselves, and demonstrates that the latter are less important than originally thought Lastly, our results show that the choice of reference (ROHF versus UHF) can have a significant impact on the accuracy of polarizabilities for open-shell systems.

  17. Assembly of liposomes controlled by triple helix formation.

    PubMed

    Jakobsen, Ulla; Vogel, Stefan

    2013-09-18

    Attachment of DNA to the surface of different solid nanoparticles (e.g., gold and silica nanoparticles) is well established, and a number of DNA-modified solid nanoparticle systems have been applied to thermal denaturation analysis of oligonucleotides. We report herein the noncovalent immobilization of oligonucleotides on the surface of soft nanoparticles (i.e., liposomes) and the subsequent controlled assembly by DNA triple helix formation. The noncovalent approach avoids tedious surface chemistry and necessary purification procedures and can simplify and extend the available methodology for the otherwise difficult thermal denaturation analysis of complex triple helical DNA assemblies. The approach is based on lipid modified triplex forming oligonucleotides (TFOs) which control the assembly of liposomes in solution in the presence of single- or double-stranded DNA targets. The thermal denaturation analysis is monitored by ultraviolet spectroscopy at submicromolar concentrations and compared to regular thermal denaturation assays in the absence of liposomes. We report on triplex forming oligonucleotides (TFOs) based on DNA and locked nucleic acid (LNA)/DNA hybrid building blocks and different target sequences (G or C-rich) to explore the applicability of the method for different triple helical assembly modes. We demonstrate advantages and limitations of the approach and show the reversible and reproducible formation of liposome aggregates during thermal denaturation cycles. Nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) show independently from ultraviolet spectroscopy experiments the formation of liposome aggregates. PMID:23885785

  18. Disinfection of immature teeth with a triple antibiotic paste.

    PubMed

    Windley, William; Teixeira, Fabricio; Levin, Linda; Sigurdsson, Asgeir; Trope, Martin

    2005-06-01

    This study assessed the efficacy of a triple antibiotic paste in the disinfection of immature dog teeth with apical periodontitis. The canals were sampled before (S1) and after (S2) irrigation with 1.25% NaOCL and after dressing with a triple antibiotic paste (S3), consisting of metronidazole, ciprofloxacin, and minocycline. At S1, 100% of the samples cultured positive for bacteria with a mean CFU count of 1.7 x 10. At S2, 10% of the samples cultured bacteria-free with a mean CFU count of 1.4 x 10. At S3, 70% of the samples cultured bacteria-free with a mean CFU count of only 26. Reductions in mean CFU counts between S1 and S2 (p < 0.0001) as well as between S2 and S3 (p < 0.0001) were statistically significant. These results indicate the effectiveness of a triple antibiotic paste in the disinfection of immature teeth with apical periodontitis. PMID:15917683

  19. New Approaches Towards Recognition of Nucleic Acid Triple Helices

    PubMed Central

    Arya, Dev P.

    2012-01-01

    We show that groove recognition of nucleic acid triple helices can be achieved with aminosugars. Among these aminosugars, neomycin is the most effective aminoglycoside (groove binder) for stabilizing a DNA triple helix. It stabilizes both the T·A·T triplex and mixed-base DNA triplexes better than known DNA minor groove binders (which usually destabilize the triplex) and polyamines. Neomycin selectively stabilizes the triplex (T·A·T and mixed base) without any effect on the DNA duplex. The selectivity of neomycin likely originates from its potential and shape complementarity to the triplex Watson–Hoogsteen groove, making it the first molecule that selectively recognizes a triplex groove over a duplex groove. The groove recognition of aminoglycosides is not limited to DNA triplexes, but also extends to RNA and hybrid triple helical structures. Intercalator–neomycin conjugates are shown to simultaneously probe the base stacking and groove surface in the DNA triplex. Calorimetric and spectrosocopic studies allow the quantification of the effect of surface area of the intercalating moiety on binding to the triplex. These studies outline a novel approach to the recognition of DNA triplexes that incorporates the use of non-competing binding sites. These principles of dual recognition should be applicable to the design of ligands that can bind any given nucleic acid target with nanomolar affinities and with high selectivity. PMID:21073199

  20. Triple X Egyptian woman and a Down's syndrome offspring.

    PubMed

    El-Dahtory, Faeza Abdel Mogib

    2013-01-01

    The 47, XXX karyotype (triple X) has a frequency of 1 in 1000 female newborns. However, this karyotype is not usually suspected at birth or childhood. Female patients with a sex chromosome abnormality may be fertile. In patients with a 47, XXX cell line there appears to be an increased risk of a cytogenetically abnormal child but the extent of this risk cannot yet be determined; it is probably lower in the non-mosaic 47, XXX patient than the mosaic 46, XX/47, XXX one. We describe a new rare case of triple X woman and a Down's syndrome offspring. The patient is 26 years of age. She is a housewife, her height is 160 cm and weight is 68 kg and her physical features and mentality are normal. She has had one pregnancy at the age of 25 years resulted in a girl with Down's syndrome. The child had 47 chromosomes with trisomy 21 (47, XX, +21) Figure 1. The patient also has 47 chromosomes with a triple X karyotype (47, XX, +X) Figure 2. The patient's husband (27 years old) is physically and mentally normal. He has 46 chromosomes with a normal XY karyotype (46, XY). There are neither Consanguinity between her parent's nor she and her husband. PMID:23901206

  1. Prenatal diagnosis and prognosis of triple X syndrome: 47, XXX.

    PubMed

    Ben Hamouda, H; Mkacher, N; Elghezal, H; Bannour, H; Kamoun, M; Soua, H; Saad, A; Souissi, M M; Sfar, M T

    2009-11-01

    Triple X syndrome is a relatively common sex chromosomal abnormality occurring in 0,1% of live-born female infants. Most of these infants have a normal phenotype and only a few cases with 47, XXX karyotype have congenital malformations. We report three cases of triple X syndrome that were diagnosed prenatally by genetic amniocentesis for advanced maternal age and have been observed from birth to age of 3 to 12 years. A description of their growth and development is presented. The birth weight was normal in all patients and one of them had facial dysmorphism with right microphtalmia and auricular septal defect. During the first 2 years of life, the neuromotor development of these infants was not distinguishable from chromosomally normal children. By 3 years of age, two patients have a moderate developmental delay in speech and language. One girl 12-year-old had normal schooling. The diagnosis of the triple X syndrome can be never made because clinical demonstrations are not rather important to arouse the demand of a karyotype. Prenatal diagnosis is often made in front of the advanced maternal age. Expectant parents must be counseled as to the significance of this 47, XXX karyotype and prognostic information must be given. PMID:19762167

  2. A theory of triple hysteresis in ferroelectric crystals

    NASA Astrophysics Data System (ADS)

    Weng, George J.

    2009-10-01

    In the vicinity of the transition temperature between two ferroelectric states, a ferroelectric crystal could exhibit a triple hysteresis under an ac field. For a BaTiO3 with the "c-plate" configuration slightly below this temperature, the middle loop is caused by the 0°→180° domain switch in the orthorhombic phase, whereas the upper and lower loops are the result of orthorhombic-to-tetragonal phase transition, and vice versa. In this article we first develop a micromechanics-based thermodynamic model to determine the thermodynamic driving force for phase transition and for domain switch as a function of electric field and temperature, and in the latter case, further supplement it with a kinetic equation and a homogenization scheme. The dependence of dielectric constant of the orthorhombic and tetragonal phases on temperature and electric field are also established. The developed theory is then applied to calculate the triple hysteresis loops of BaTiO3 at several levels of temperature. The calculated results for the triple loops, and for the variation of dielectric constant, are found to be in full accord with the test data of Huibregtse and Young [Phys. Rev. 103, 1705 (1956)].

  3. Integrating Compassionate, Collaborative Care (the "Triple C") Into Health Professional Education to Advance the Triple Aim of Health Care.

    PubMed

    Lown, Beth A; McIntosh, Sharrie; Gaines, Martha E; McGuinn, Kathy; Hatem, David S

    2016-03-01

    Empathy and compassion provide an important foundation for effective collaboration in health care. Compassion (the recognition of and response to the distress and suffering of others) should be consistently offered by health care professionals to patients, families, staff, and one another. However, compassion without collaboration may result in uncoordinated care, while collaboration without compassion may result in technically correct but depersonalized care that fails to meet the unique emotional and psychosocial needs of all involved. Providing compassionate, collaborative care (CCC) is critical to achieving the "triple aim" of improving patients' health and experiences of care while reducing costs. Yet, values and skills related to CCC (or the "Triple C") are not routinely taught, modeled, and assessed across the continuum of learning and practice. To change this paradigm, an interprofessional group of experts recently recommended approaches and a framework for integrating CCC into health professional education and postgraduate training as well as clinical care. In this Perspective, the authors describe how the Triple C framework can be integrated and enhance existing competency standards to advance CCC across the learning and practice continuum. They also discuss strategies for partnering with patients and families to improve health professional education and health care design and delivery through quality improvement projects. They emphasize that compassion and collaboration are important sources of professional, patient, and family satisfaction as well as critical aspects of professionalism and person-centered, relationship-based high-quality care. PMID:26717505

  4. Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling

    PubMed Central

    2014-01-01

    Background Triple negative breast cancer (TNBC) is characterized by lack of expression of both estrogen and progesterone receptor as well as lack of overexpression or amplification of HER2. Despite an increased probability of response to chemotherapy, many patients resistant to current chemotherapy regimens suffer from a worse prognosis compared to other breast cancer subtypes. However, molecular determinants of response to chemotherapy specific to TNBC remain largely unknown. Thus, there is a high demand for biomarkers potentially stratifying triple negative breast cancer patients for neoadjuvant chemotherapies or alternative therapies. Methods In order to identify genes correlating with both the triple negative breast cancer subtype as well as response to neoadjuvant chemotherapy we employed publicly available gene expression profiles of patients, which had received neoadjuvant chemotherapy. Analysis of tissue microarrays as well as breast cancer cell lines revealed correlation to the triple negative breast cancer subtype. Subsequently, effects of siRNA-mediated knockdown on response to standard chemotherapeutic agents as well as radiation therapy were analyzed. Additionally, we evaluated the molecular mechanisms by which SFRP1 alters the carcinogenic properties of breast cancer cells. Results SFRP1 was identified as being significantly overexpressed in TNBC compared to other breast cancer subtypes. Additionally, SFRP1 expression is significantly correlated with an increased probability of positive response to neoadjuvant chemotherapy. Knockdown of SFRP1 in triple negative breast cancer cells renders the cells more resistant to standard chemotherapy. Moreover, tumorigenic properties of the cells are modified by knockdown, as shown by both migration or invasion capacity as well reduced apoptotic events. Surprisingly, we found that these effects do not rely on Wnt signaling. Furthermore, we show that pro-apoptotic as well as migratory pathways are differentially

  5. Triple junctions and multi-directional extension of the lithosphere

    NASA Astrophysics Data System (ADS)

    Gerya, Taras; Burov, Evgenii

    2016-04-01

    Triple junctions are among the most remarkable features of global plate tectonics but their nucleation and evolution remains debatable. Divergent (R-R-R) triple junctions (at 120o and T junctions) are particular ones since their stability depends on the exact values of the relative velocities of multi-directional plate motions and hence is strongly affected by plate rheology and processes of crustal and lithospheric accretion. It is commonly accepted (although not quantitatively tested) that the geometry and stability of R-R-R triple junctions should be related to the intuitive geometric considerations that 3-branch configurations should be more "stable" compared to >3-branch configurations (e.g. quadruple junctions) under conditions of long-term multi-directional extension on a 3D Earth surface. Indeed, it has been long-time suggested that triple junctions result from evolution of short-lived quadruple junctions, yet, without providing a consistent mechanical explanation or experimental demonstration of this process, due to the rheological complexity of the breaking lithosphere subsequently subjected to complex oceanic crustal and lithospheric accretion processes. Therefore, a complete 3D thermo-mechanically consistent approach is needed to understand the processes of formation of multi-branch junctions. Here, we study numerically the processes of multi-branch junctions formation under condition of multi-directional lithospheric extension. We use high-resolution 3D numerical magmatic-thermo-mechanical experiments that take into account realistic thermo-rheological structure and rheology of the lithosphere and account for crustal and lithospheric accretion processes. We find that two major types of quadruple and triple junctions are formed under bi-directional or multidirectional far-field stress field: (1) plate rifting junctions are formed by the initial plate fragmentation and can be subsequently re-arranged into (2) oceanic spreading junctions controlled by the

  6. Nintedanib, a novel triple angiokinase inhibitor for the treatment of non-small cell lung cancer.

    PubMed

    Noonan, S; Man Wong, K; Jimeno, A

    2015-06-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. Recent advances involving targeted therapies are promising, but most patients do not have an "oncogene addicted" disease. A platinum doublet chemotherapy regimen has been the mainstay of therapy since 1997. The addition of antiangiogenic agents to traditional chemotherapy has improved survival in patients with non-small cell lung cancer. However, these agents are limited by serious adverse events such as thromboembolism, bowel perforation and hemorrhage and by the development of resistance. Nintedanib is a novel, orally available triple angiokinase inhibitor that targets three important pathways involved in the initiation and propagation of angiogenesis in tumors, the VEGF, FGF and PDGFR pathways. Phase I and II trials have identified the maximum tolerated dose in monotherapy and in combination with traditional chemotherapy. The toxicity profile is tolerable and reversible, dominated by transaminitis and gastrointestinal side effects. The phase III LUME-lung 1 study (NCT00805194) compared docetaxel, a standard treatment in the second line, with docetaxel in combination with nintedanib. Progression-free survival was 3.4 months in the combination group compared to 2.7 months in the docetaxel group, (HR 0.79, 95% CI 0.68-0.92, P = 0.0019). There was a significant improvement in overall survival in adenocarcinoma patients, 12.6 vs. 10.3 months (HR 0.83, 95% CI 0.7-0.99, P = 0.036). Based on the results of this study, nintedanib has been approved by the EMA in Europe, as a second-line treatment in patients with adenocarcinoma. It is a promising, well-tolerated therapy that is currently being investigated in multiple different tumor types. PMID:26261849

  7. Sensitizing Triple-Negative Breast Cancer to PI3K Inhibition by Cotargeting IGF1R.

    PubMed

    de Lint, Klaas; Poell, Jos B; Soueidan, Hayssam; Jastrzebski, Katarzyna; Vidal Rodriguez, Jordi; Lieftink, Cor; Wessels, Lodewyk F A; Beijersbergen, Roderick L

    2016-07-01

    Targeted therapies have proven invaluable in the treatment of breast cancer, as exemplified by tamoxifen treatment for hormone receptor-positive tumors and trastuzumab treatment for HER2-positive tumors. In contrast, a subset of breast cancer negative for these markers, triple-negative breast cancer (TNBC), has met limited success with pathway-targeted therapies. A large fraction of TNBCs depend on the PI3K pathway for proliferation and survival, but inhibition of PI3K alone generally has limited clinical benefit. We performed an RNAi-based genetic screen in a human TNBC cell line to identify kinases whose knockdown synergizes with the PI3K inhibitor GDC-0941 (pictilisib). We discovered that knockdown of insulin-like growth factor-1 receptor (IGF1R) expression potently increased sensitivity of these cells to GDC-0941. Pharmacologic inhibition of IGF1R using OSI-906 (linsitinib) showed a strong synergy with PI3K inhibition. Furthermore, we found that the combination of GDC-0941 and OSI-906 is synergistic in 8 lines from a panel of 18 TNBC cell lines. In these cell lines, inhibition of IGF1R further decreases the activity of downstream PI3K pathway components when PI3K is inhibited. Expression analysis of the panel of TNBC cell lines indicates that the expression levels of IGF2BP3 can be used as a potential predictor for sensitivity to the PI3K/IGF1R inhibitor combination. Our data show that combination therapy consisting of PI3K and IGF1R inhibitors could be beneficial in a subset of TNBCs. Mol Cancer Ther; 15(7); 1545-56. ©2016 AACR. PMID:27196766

  8. Drug therapy for the patient with resistant hypertension.

    PubMed

    Donazzan, Luca; Ewen, Sebastian; Papademetriou, Vasilios; Linicus, Yvonne; Linz, Dominik; Böhm, Michael; Mahfoud, Felix

    2015-03-01

    Resistant hypertension is associated with high morbidity and mortality. Resistant hypertension is defined as blood pressure above targets despite treatment with at least three antihypertensive drugs in adequate dose and combination. Nonadherence is a frequent cause of uncontrolled hypertension and can be improved by providing fixed dose (of two or three agents) single pill combination. Triple combination of the most widely used antihypertensive agents (renin-angiotensin-aldosterone system antagonists, calcium channel blockers and diuretics) is a safe and effective therapy. Fourth line therapy is the use of an aldosterone antagonist. Renal denervation and baroreceptor stimulation can be considered in patients who remained uncontrolled despite optimal medical therapy. PMID:25760878

  9. Guide to Understanding Triple-Negative Breast Cancer

    MedlinePlus

    ... Diet, Nutrition and Exercise Expressive Writing Guided Imagery Hypnosis Massage Therapy Mindfulness-Based Stress Reduction Yoga and ... Diet, Nutrition and Exercise Expressive Writing Guided Imagery Hypnosis Massage Therapy Mindfulness-Based Stress Reduction Yoga and ...

  10. Radiation therapy

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001918.htm Radiation therapy To use the sharing features on this page, please enable JavaScript. Radiation therapy uses high-powered x-rays, particles, or ...

  11. Alternative Therapies

    MedlinePlus

    ... Late Effects of Poliomyelitis for Physicians and Survivors © Alternative Therapies Alternative therapies, also called complementary, can support ... of motion, pain, and fatigue are often reported. Energy work includes acupuncture and acupressure, traditional Chinese medicine ...

  12. Radiation Therapy

    MedlinePlus

    Radiation therapy is a cancer treatment. It uses high doses of radiation to kill cancer cells and stop them ... places inside your body. The type of radiation therapy you receive depends on many factors, including The ...

  13. Radiation Therapy

    MedlinePlus

    ... people who have radiation therapy may feel more tired than usual, not feel hungry, or lose their ... of radiation therapy include: Fatigue. Fatigue, or feeling tired, is the most common side effect of radiation ...

  14. Feminist Therapy.

    ERIC Educational Resources Information Center

    Laidlaw, Toni; Malmo, Cheryl

    1991-01-01

    Traces roots of feminist therapy and its independence from traditional and prevalent theories and therapy practices. Asserts that Freudian theory and humanistic assumptions are sexist and contribute to powerlessness of women. In contrast, feminist therapy is seen as dealing directly with client-counselor relationships, trust, advocacy, and…

  15. Stabilization of Collagen-Model, Triple-Helical Peptides for In Vitro and In Vivo Applications

    PubMed Central

    Bhowmick, Manishabrata; Fields, Gregg B.

    2014-01-01

    The triple-helical structure of collagen has been accurately reproduced in numerous chemical and recombinant model systems. Triple-helical peptides and proteins have found application for dissecting collagen-stabilizing forces, isolating receptor- and protein-binding sites in collagen, mechanistic examination of collagenolytic proteases, and development of novel biomaterials. Introduction of native-like sequences into triple-helical constructs can reduce the thermal stability of the triple-helix to below that of the physiological environment. In turn, incorporation of nonnative amino acids and/or templates can enhance triple-helix stability. We presently describe approaches by which triple-helical structure can be modulated for use under physiological or near-physiological conditions. PMID:24014440

  16. Should quinolones come first in Helicobacter pylori therapy?

    PubMed Central

    Berning, Marco; Krasz, Susanne; Miehlke, Stephan

    2011-01-01

    New generations of fluoroquinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against Gram-positive and Gram-negative bacteria, and have been successfully introduced into the treatment of Helicobacter pylori infection. Based on a large body of evidence, current guidelines recommend the use of levofloxacin- or moxifloxacin-containing proton-pump inhibitor (PPI) triple therapies in second-line or rescue treatment of H. pylori infection. The efficacy of standard PPI triple therapies has substantially declined during the last decade, mainly due to increasing resistance against the key antibiotics clarithromycin and metronidazole. Therefore, alternative strategies for first-line therapy of H. pylori infection have been evaluated in a considerable number of clinical trials including sequential regimens, nonbismuth quadruple regimens, and quinolone-containing PPI triple therapy regimens. The aim of this paper is to summarize the current body of evidence of levofloxacin- and moxifloxacin-containing regimens in first-line treatment of H. pylori infection, and to discuss the risks and benefits of these strategies in the light of increasing resistance of H. pylori to quinolones. PMID:21694812

  17. Simulations of magnetic field gradients due to micro-magnets on a triple quantum dot circuit

    NASA Astrophysics Data System (ADS)

    Poulin-Lamarre, G.; Bureau-Oxton, C.; Kam, A.; Zawadzki, P.; Studenikin, S.; Aers, G.; Pioro-Ladrière, M.; Sachrajda, A. S.

    2013-12-01

    To quantify the effects of local magnetic fields on triple quantum dots, the Heisenberg Hamiltonian has been diagonalized for three electrons coupled via the exchange interaction. In particular, we have investigated different geometries of micro-magnets located on top of the triple dot in order to optimize the field gradient characteristics. In this paper, we focus on two geometries which are candidates for an addressable EDSR triple quantum dot device.

  18. Simulations of magnetic field gradients due to micro-magnets on a triple quantum dot circuit

    SciTech Connect

    Poulin-Lamarre, G.; Bureau-Oxton, C.; Kam, A.; Zawadzki, P.; Aers, G.; Studenikin, S.; Pioro-Ladrière, M.; Sachrajda, A. S.

    2013-12-04

    To quantify the effects of local magnetic fields on triple quantum dots, the Heisenberg Hamiltonian has been diagonalized for three electrons coupled via the exchange interaction. In particular, we have investigated different geometries of micro-magnets located on top of the triple dot in order to optimize the field gradient characteristics. In this paper, we focus on two geometries which are candidates for an addressable EDSR triple quantum dot device.

  19. Triple negative breast cancer - our experience and review.

    PubMed

    Krishnamurthy, S; Poornima, R; Challa, Vasu Reddy; Goud, Y G Basavana

    2012-03-01

    Triple negative breast cancer (TNBC) constitutes 10-25% of patients with breast cancer. TNBC is an aggressive phenotype affecting younger age groups and has poor prognosis. We retrospectively analysed 50 triple negative breast cancer patients attending our outpatient department among 270 breast cancer patients. The incidence of TNBC was 18.5%, and most of them were premenopausal 56% (28/50) with mean age was 46.66 ± 13.87 (Range 28-72 years). Most of them had Invasive ductal cancer 94% (47/50) and were high grade (Grade 3-96%)(48/50). Five patients presented with metastatic disease (2 patients only Skeletal, 1 patient with Skeletal and Lung, 1 patient with Lung and 1 patient with Liver) and 7 patients developed recurrence (all 7 had chest wall recurrence, 3 had supraclavicular lymph node recurrence, 2 had skeletal metastases and 1 had developed brain metastases) during follow up. The mean disease free survival was 15 months (Range 3-58 months) and overall survival was 20.14 months (Range 5-70 months). Fifty six percent (28/50) of patients were premenopausal and mean age of presentation was 46.66 ± 13.87 years (Range 28-72 years). Ten percent (5/50) presented with metastatic disease and 15% (7/45) developed metastases during follow up. Five patients (10%) died during follow up. Hence, Triple negative breast cancer is aggressive, with rapid progression leading to mortality in younger patients. PMID:23449631

  20. Triple Tobacco Screen Opportunity to Help Families Become Smokefree

    PubMed Central

    Nabi-Burza, Emara; Winickoff, Jonathan P.; Finch, Stacia; Regan, Susan

    2013-01-01

    Background American Academy of Pediatrics policy recommends that pediatricians document environmental tobacco smoke (ETS) exposure of a child at every visit. The extent to which pediatricians adhere to this policy, however, is unknown. Purpose The goal of the study was to examine the extent to which pediatricians screen parents for tobacco use and home- and car-related smoking rules. Further, the potential association between factors associated with pediatrician inquiry into parental tobacco use and rules is examined. Methods Post-visit exit interviews were conducted in ten pediatric practices between June 2009 and March 2011 with parents whose children had been seen by a healthcare provider. Parents were considered to have been given the “triple tobacco screen” if they reported being asked by a pediatric healthcare provider about their smoking behavior, smokefree home rules, and smokefree car rules. Bivariate analysis and multivariable logistic regression was done to explore factors associated with parents being given any component of the triple tobacco screening. Data were analyzed between March 2012 and February 2013. Results Of 9145 parents interviewed, 20% of the parents reported being asked at least one question from the triple tobacco screen, and only 9% reported being asked all three questions. Overall, 17% of parents reported being asked about their smoking status, 16% about smokefree home rules, and 11% about smokefree car rules. Few smoking parents (23%) and fewer nonsmoking parents (19%) were screened about their tobacco use and behavior. Conclusions Pediatricians infrequently addressed ETS exposure of children among parents who do and do not smoke. Substantial missed opportunities may exist to counsel smokers and reduce ETS exposure of children in the most common exposure locations—the home and car. PMID:24237914

  1. Tectonic setting of the Mendocino triple junction region

    SciTech Connect

    Clarke, S.H. Jr.; McLaughlin, R.J. ); Carver, G.A.; Burke, R.M.; McPherson, R.C. )

    1993-04-01

    Onshore and offshore geologic mapping coupled with topical investigations constrain the tectonic relations and geometry of active plate boundaries in the Mendocino triple junction region. Along the northern California coast and offshore, Gorda-North American plate convergence is reflected by youthful west- to northwest-verging thrust fault systems that extend to or near the plate interface at depth. Interplate coupling across a minimum breadth of 70--80 km is indicated by late Quaternary uplift and shortening rates, the nature and distribution of upper and lower plate seismicity, divergent trends in upper plate structures, and a history of large late Holocene earthquakes. Offshore seismic-reflection and seismicity data from the vicinity of the Mendocino fault (MF) show that the fault dips steeply to the north, and that the older, relatively rigid Pacific plate acts as a buttress against which the southern Gorda plate is being deformed. Onshore investigations show that the San Andreas fault zone (SAF) extends on land southeast of Point Delgada (at Whale Gulch), and is manifested along the north and northeast side of the King Range (KR) by north-northeast-vergent thrust faults. This thrust fault system may root into the steeply dipping offshore San Andreas fault. Faults of this system may include active, blind northeast-vergent thrusts that extend from a root zone beneath the King Range northward and upward into Franciscan Complex (Coastal belt) rocks along the north flank of the range. The southern Cascadia subduction zone megathrust intersects the Mendocino and San Andreas transform faults in the Mendocino triple junction. The upper crustal location of this intersection lies nearshore and/or landward along the north flank of the King Range. An area of focused rapid uplift and repeated coseismic growth (Mendocino Uplift) straddles the triple junction.

  2. Pharmacological and Behavioral Characterization of D-473, an Orally Active Triple Reuptake Inhibitor Targeting Dopamine, Serotonin and Norepinephrine Transporters

    PubMed Central

    Dutta, Aloke K.; Santra, Soumava; Sharma, Horrick; Voshavar, Chandrashekhar; Xu, Liping; Mabrouk, Omar; Antonio, Tamara; Reith, Maarten E. A.

    2014-01-01

    Major depressive disorder (MDD) is a debilitating disease affecting a wide cross section of people around the world. The current therapy for depression is less than adequate and there is a considerable unmet need for more efficacious treatment. Dopamine has been shown to play a significant role in depression including production of anhedonia which has been one of the untreated symptoms in MDD. It has been hypothesized that drugs acting at all three monoamine transporters including dopamine transporter should provide more efficacious antidepressants activity. This has led to the development of triple reuptake inhibitor D-473 which is a novel pyran based molecule and interacts with all three monoamine transporters. The monoamine uptake inhibition activity in the cloned human transporters expressed in HEK-293 cells (70.4, 9.18 and 39.7 for DAT, SERT and NET, respectively) indicates a serotonin preferring triple reuptake inhibition profile for this drug. The drug D-473 exhibited good brain penetration and produced efficacious activity in rat forced swim test under oral administration. The optimal efficacy dose did not produce any locomotor activation. Microdialysis experiment demonstrated that systemic administration of D-473 elevated extracellular level of the three monoamines DA, 5-HT, and NE efficaciously in the dorsal lateral striatum (DLS) and the medial prefrontal cortex (mPFC) area, indicating in vivo blockade of all three monoamine transporters by D-473. Thus, the current biological data from D-473 indicate potent antidepressant activity of the molecule. PMID:25427177

  3. A priori precision estimation for neutron triples counting

    SciTech Connect

    Croft, S.; Swinhoe, M. T.; Henzl, V.

    2011-07-01

    The nondestructive assay of Plutonium bearing items for criticality, safety, security, safeguards, inventory balance, process control, waste management and compliance is often undertaken using correlated neutron counting. In particular Multiplicity Shift Register analysis allows one to extract autocorrelation parameters from the pulse train which can, within the framework of a simple interpretational model, be related to the effective {sup 240}Pu spontaneous fission mass present. The effective {sup 240}Pu mass is a weighted sum of the {sup 238}Pu, {sup 240}Pu and {sup 242}Pu masses so if the relative isotopic composition of the Pu can be established from the measured {sup 240}Pu effective mass one can estimate the total Pu mass and also the masses of the individual isotopes, example the fissile species {sup 239}Pu and {sup 241}Pu. In multiplicity counting three counting rates are obtained. These are the Singles, Doubles and Triples rates. The Singles rate is just the gross, totals or trigger rate. The Doubles and Triples rates are calculated from factorial moments of the observed signal triggered neutron multiplicity distributions following spontaneous fission in the item and can be thought of as the rate of observed coincident pairs and coincident triplets on the pulse train. Coincident events come about because the spontaneous fission and induced fission chains taking place in the item result in bursts of neutrons. These remain time correlated during the detection process and so retain information, through the burst size distribution, about the Pu content. In designing and assessing the performance of a detector system to meet a given goal it is necessary to make a priori estimates of the counting precision for all three kinds of rates. This is non-trivial because the counting does not obey the familiar rules of a Poissonian counting experiment because the pulse train has time correlated events on it and the train is sampled by event triggered gates that may

  4. Triple Negative Breast Cancer Team Project — EDRN Public Portal

    Cancer.gov

    Triple negative breast cancers (TNBC), comprise 15-20% of breast cancers, and are associated with later stage at diagnosis, increased mortality, and occur more frequently in younger women where mammographic screening is less reliable. TNBCs are more likely to be diagnosed by physical exam than by mammographic screening. There is an unmet clinical need for biomarkers for the early detection of TNBC. Here, we are proposing the development of a plasma-based biomarker panel for the routine screening of women over the age of 40 for TNBC that can be used to identify women for further imaging.

  5. Controllable optomechanical coupling in serially-coupled triple resonators

    SciTech Connect

    Huang, Chenguang Zhao, Yunsong; Fan, Jiahua; Zhu, Lin

    2014-12-15

    Radiation pressure can efficiently couple mechanical modes with optical modes in an optical cavity. The coupling efficiency is quite dependent on the interaction between the optical mode and mechanical mode. In this report, we investigate a serially-coupled triple resonator system, where a freestanding beam is placed in the vicinity of the middle resonator. In this coupled system, we demonstrate that the mechanical mode of the free-standing beam can be selectively coupled to different resonance supermodes through the near field interaction.

  6. Triple coincidence PALS setup based on fast pulse digitizers

    NASA Astrophysics Data System (ADS)

    Bosnar, D.; Đurđević, B.; Pavelić, L.; Bosnar, S.

    2015-06-01

    We have assembled positron annihilation lifetime spectroscopy system that consists of three BaF2 detectors with XP2020URQ PMTs which are directly coupled to DRS4 evaluation board. Both time and energy information of the detected gamma rays are reconstructed. In the off-line analysis, by using selected cuts on energies of gamma rays, double, as well as triple coincidence events can be extracted. The setup is very suitable for the determination of contributions of positronium three gamma annihilations which can be of interest in the investigations of various porous materials.

  7. An acoustic vibration sensor based on tapered triple cladding fiber

    NASA Astrophysics Data System (ADS)

    Xu, Hui; Pang, Fufei; Zhao, Shiqi; Chen, Zhenyi; Wang, Tingyun

    2014-05-01

    An acoustic vibration sensor is investigated and demonstrated by using a tapered triple cladding fiber (TCF). It is fabricated by tapering a length of 2 cm TCF which is spliced between two single mode fibers (SMF). The TCF consists of core, inner cladding, middle cladding and outer cladding. After the tapering process, this structure becomes a tapered coaxial fiber coupler which presents a periodic filtering transmission spectrum. The surrounding vibration perturbation can be directly demodulated by intensity detection of the transmission power at a particular wavelength. The experimental result shows that the maximum frequency response of 700 kHz is achieved.

  8. Determining triple gauge boson couplings from Higgs data.

    PubMed

    Corbett, Tyler; Éboli, O J P; Gonzalez-Fraile, J; Gonzalez-Garcia, M C

    2013-07-01

    In the framework of effective Lagrangians with the SU(2)(L)×U(1)(Y) symmetry linearly realized, modifications of the couplings of the Higgs field to the electroweak gauge bosons are related to anomalous triple gauge couplings (TGCs). Here, we show that the analysis of the latest Higgs boson production data at the LHC and Tevatron give rise to strong bounds on TGCs that are complementary to those from direct TGC analysis. We present the constraints on TGCs obtained by combining all available data on direct TGC studies and on Higgs production analysis. PMID:23862992

  9. Hydrothermal Exploration at the Chile Triple Junction - ABE's last adventure?

    NASA Astrophysics Data System (ADS)

    German, C. R.; Shank, T. M.; Lilley, M. D.; Lupton, J. E.; Blackman, D. K.; Brown, K. M.; Baumberger, T.; Früh-Green, G.; Greene, R.; Saito, M. A.; Sylva, S.; Nakamura, K.; Stanway, J.; Yoerger, D. R.; Levin, L. A.; Thurber, A. R.; Sellanes, J.; Mella, M.; Muñoz, J.; Diaz-Naveas, J. L.; Inspire Science Team

    2010-12-01

    In February and March 2010 we conducted preliminary exploration for hydrothermal plume signals along the East Chile Rise where it intersects the continental margin at the Chile Triple Junction (CTJ). This work was conducted as one component of our larger NOAA-OE funded INSPIRE project (Investigation of South Pacific Reducing Environments) aboard RV Melville cruise MV 1003 (PI: Andrew Thurber, Scripps) with all shiptime funded through an award of the State of California to Andrew Thurber and his co-PI's. Additional support came from the Census of Marine Life (ChEss and CoMarge projects). At sea, we conducted a series of CTD-rosette and ABE autonomous underwater vehicle operations to prospect for and determine the nature of any seafloor venting at, or adjacent to, the point where the the East Chile Rise subducts beneath the continental margin. Evidence from in situ sensing (optical backscatter, Eh) and water column analyses of dissolved CH4, δ3He and TDFe/TDMn concentrations document the presence of two discrete sites of venting, one right at the triple junction and the other a further 10km along axis, north of the Triple Junction, but still within the southernmost segment of the East Chile Rise. From an intercomparison of the abundance of different chemical signals we can intercompare likely characteristics of these differet source sites and also differentiate between them and the high methane concentrations released from cold seep sites further north along the Chile Margin, both with the CTJ region and also at the Concepcion Methane Seep Area (CMSA). This multi-disciplinary and international collaboration - involving scientists from Chile, the USA, Europe and Japan - can serve as an excellent and exciting launchpoint for wide-ranging future investigations of the Chile Triple Junction area - the only place on Earth where an oceanic spreading center is being actively subducted beneath a continent and also the only place on Earth where all known forms of deep

  10. Triple-phase bone image abnormalities in Lyme arthritis

    SciTech Connect

    Brown, S.J.; Dadparvar, S.; Slizofski, W.J.; Glab, L.B.; Burger, M. )

    1989-10-01

    Arthritis is a frequent manifestation of Lyme disease. Limited triple-phase Tc-99m MDP bone imaging of the wrists and hands with delayed whole-body images was performed in a patient with Lyme arthritis. This demonstrated abnormal joint uptake in the wrists and hands in all three phases, with increased activity seen in other affected joints on delayed whole-body images. These findings are nonspecific and have been previously described in a variety of rheumatologic conditions, but not in Lyme disease. Lyme disease should be considered in the differential diagnosis of articular and periarticular bone scan abnormalities.

  11. Mesoscopic Ensembles of Polar Bosons in Triple-Well Potentials

    SciTech Connect

    Lahaye, T.; Pfau, T.; Santos, L.

    2010-04-30

    Mesoscopic dipolar Bose gases in triple-well potentials offer a minimal system for the analysis of the nonlocal character of the dipolar interaction. We show that this nonlocal character may be clearly revealed by a variety of possible ground-state phases. In addition, an appropriate control of short-range and dipolar interactions may lead to novel scenarios for the dynamics of polar bosons in lattices, including the dynamical creation of mesoscopic quantum superpositions, which may be employed in the design of Heisenberg-limited atom interferometers.

  12. Coherent control of atomic tunneling in a driven triple well

    SciTech Connect

    Lu Gengbiao; Hai Wenhua; Xie Qiongtao

    2011-01-15

    Coherent control of quantum tunneling is investigated for a single atom held in a driven triple-well potential without tight-binding approximation. In the high-frequency regime within or without multiphoton resonance, we find the analytical solutions and their numerical correspondences, including the special Floquet states of invariant populations and the non-Floquet states of slowly varying populations. The Floquet quasienergy spectrum exhibits anticrossings and crossings for different values of the driving parameters, which are associated with different tunneling properties described by the non-Floquet states. Applying the presented results, we suggest a scheme for transporting a single atom between nonadjacent wells or between adjacent wells.

  13. Triple-material stress-strain resistivity gage

    DOEpatents

    Stout, R.B.

    1988-05-17

    A triple material piezoresistive gage provides multi-component elastic stress measurements is disclosed. Thin foils of three piezoresistive materials, e.g. ytterbium, manganin, and constantan, are configured in a nested serpentine rectilinear grid or other grid arrangement and embedded in a medium, preferably normal to the direction of shock wave propagation. The output of the gage is a resistivity change history for each material of the gage. Each resistivity change is independent of the others so that three diagonal components of the elastic stress or strain tensor can be calculated from the resistivity measurements. 4 figs.

  14. Triple-material stress-strain resistivity gage

    DOEpatents

    Stout, R.B.

    1987-05-19

    A triple material piezoresistive gage provides multi-component elastic stress or strain measurements. Thin foils of three piezoresistive materials, e.g., ytterbium, manganin, and constantan, are configured in a nested serpentine rectilinear grind or other grind arrangement and embedded in a medium, preferably normal to the direction of shock wave propagation. The output of the gage is a resistivity change history for each material of gage. Each resistivity change is independent of the others so that three diagonal components of the elastic stress or strain tensor can be calculated form the resistivity measurements. 4 figs.

  15. Triple-material stress-strain resistivity gage

    DOEpatents

    Stout, Ray B.

    1988-01-01

    A triple material piezoresistive gage provides multi-component elastic stress or measurements. Thin foils of three piezoresistive materials, e.g. ytterbium, manganin, and constantan, are configured in a nested serpentine rectilinear grid or other grid arrangement and embedded in a medium, preferably normal to the direction of shock wave propagation. The output of the gage is a resistivity change history for each material of the gage. Each resistivity change is independent of the others so that three diagonal components of the elastic stress or strain tensor can be calculated from the resistivity measurements.

  16. Electrically Protected Resonant Exchange Qubits in Triple Quantum Dots

    NASA Astrophysics Data System (ADS)

    Taylor, J. M.; Srinivasa, V.; Medford, J.

    2013-08-01

    We present a modulated microwave approach for quantum computing with qubits comprising three spins in a triple quantum dot. This approach includes single- and two-qubit gates that are protected against low-frequency electrical noise, due to an operating point with a narrowband response to high frequency electric fields. Furthermore, existing double quantum dot advances, including robust preparation and measurement via spin-to-charge conversion, are immediately applicable to the new qubit. Finally, the electric dipole terms implicit in the high frequency coupling enable strong coupling with superconducting microwave resonators, leading to more robust two-qubit gates.

  17. Charge Kondo effect in a triple quantum dot

    NASA Astrophysics Data System (ADS)

    Yoo, Gwangsu; Park, Jinhong; Lee, S. S.-B.; Sim, H.-S.

    2014-03-01

    We predict that the charge Kondo effect appears in a triangular triple quantum dot. The system has two-fold degenerate ground-state charge configurations, interdot Coulomb interactions, lead-dot electron tunnelings, but no interdot electron tunneling. We show, using bosonization and refermionization, that the system is described by the anisotropic Kondo model. The anisotropy can be tuned by changing lead-dot electron tunneling strength, which allows one to experimentally explore the transition between the ferromagnetic non-Fermi liquid and antiferromagnetic Kondo phases in the Kondo phase diagram. Using numerical renormalization group method, we demonstrate that the transition is manifested in electron conductances through the dot.

  18. Spin-orbit effects in a triple quantum dot shuttle

    NASA Astrophysics Data System (ADS)

    Villavicencio, J.; Maldonado, I.; Cota, E.; Platero, G.

    2013-12-01

    Spin transport properties of a triple quantum dot shuttle system are analyzed in the presence of spin-orbit interaction. We calculate the spin current through the device as a function of the bias voltage detuning. We find that new resonances in the current through the shuttle appear due to the presence of spin-orbit interaction, and the states involved in the conduction process are identified. Also, spin current polarization is analyzed as a function of tunnel coupling and detuning, and conditions are found where the device can act as a spin filter.

  19. Electrically protected resonant exchange qubits in triple quantum dots.

    PubMed

    Taylor, J M; Srinivasa, V; Medford, J

    2013-08-01

    We present a modulated microwave approach for quantum computing with qubits comprising three spins in a triple quantum dot. This approach includes single- and two-qubit gates that are protected against low-frequency electrical noise, due to an operating point with a narrowband response to high frequency electric fields. Furthermore, existing double quantum dot advances, including robust preparation and measurement via spin-to-charge conversion, are immediately applicable to the new qubit. Finally, the electric dipole terms implicit in the high frequency coupling enable strong coupling with superconducting microwave resonators, leading to more robust two-qubit gates. PMID:23952376

  20. Dynamical formation and scattering of hierarchical triples: cross-sections, Kozai-Lidov oscillations, and collisions

    NASA Astrophysics Data System (ADS)

    Antognini, Joseph M. O.; Thompson, Todd A.

    2016-03-01

    Dynamical scattering of binaries and triple systems of stars, planets, and compact objects may produce highly inclined triple systems subject to Kozai-Lidov (KL) oscillations, potentially leading to collisions, mergers, Type Ia supernovae, and other phenomena. We present the results of more than 400 million gravitational scattering experiments of binary-binary, triple-single, and triple-binary scattering. We compute the cross-sections for all possible outcomes and explore their dependences on incoming velocity, mass, semimajor axis, and eccentricity, including analytic fits and discussion of the velocity dependence. For the production of new triple systems by scattering we find that compact triples are preferred, with ratios of outer to inner semimajor axes of ˜few-100, flat or quasi-thermal eccentricity distributions, and flat distributions in cosine of the mutual inclination. Dynamically formed triples are thus subject to strong KL oscillations, the `eccentric Kozai mechanism', and non-secular effects. For single and binary flyby encounters with triple systems, we compute the cumulative cross-section for changes to the mutual inclination, eccentricity, and semimajor axis ratio. We apply these results to scattering events in the field, open clusters, and globular clusters, and explore the implications for Type Ia supernovae via collisions and mergers, stellar collisions, and the lifetime and dynamical isolation of triple systems undergoing KL oscillations. An appendix provides an analysis of the velocity dependence of the collision cross-section in binary-single scattering.

  1. Three cases of triple A syndrome (Allgrove syndrome) in pediatric surgeons' view.

    PubMed

    Erginel, Başak; Gün, Feryal; Kocaman, Hakan; Çelik, Alaadin; Salman, Tansu

    2016-04-01

    Triple A syndrome, also known as Allgrove syndrome, is a rare disease, and presents mainly in children. Its cardinal symptoms are achalasia, alacrima, and adrenocorticotropic hormone (ACTH) insensitivity. We report three cases of Triple A syndrome. Our aim is to inform pediatric surgeons about the existence of this rare syndrome and to highlight the need for suspicion of alacrima and ACTH insensitivity in cases of pediatric achalasia. Triple A syndrome should be considered in patients presenting with achalasia. Alacrima should be investigated by a Schirmer test, and adrenal dysfunction should be tested in cases of suspected triple A. PMID:27385299

  2. Folliculitis decalvans of the scalp: response to triple therapy with isotretinoin, clindamycin, and prednisolone.

    PubMed

    Gemmeke, Astrid; Wollina, Uwe

    2006-12-01

    Folliculitis decalvans of the scalp is a recurrent, purulent follicular inflammation leading to scarring alopecia. We report on a 27-year-old man with folliculitis decalvans successfully treated with a combination of isotretinoin, corticosteroids, and clindamycin. PMID:17982613

  3. Pharmacological profiling of kinase dependency in cell lines across triple-negative breast cancer subtypes

    PubMed Central

    Fink, Lauren S.; Beatty, Alexander; Devarajan, Karthik; Peri, Suraj; Peterson, Jeffrey R.

    2014-01-01

    Triple-negative breast cancers (TNBC), negative for estrogen receptor, progesterone receptor, and Her2 amplification, are resistant to standard targeted therapies and exhibit a poor prognosis. Furthermore, they are highly heterogeneous with respect to genomic alterations, and common therapeutic targets are lacking though substantial evidence implicates dysregulated kinase signaling. Recently, six subtypes of TNBC were identified based on gene expression and were proposed to predict sensitivity to a variety of therapeutic agents including kinase inhibitors. To test this hypothesis, we screened a large collection of well-characterized, small-molecule kinase inhibitors for growth inhibition in a panel of TNBC cell lines representing all six subtypes. Sensitivity to kinase inhibition correlated poorly with TNBC subtype. Instead, unsupervised clustering segregated TNBC cell lines according to clinically relevant features including dependence on epidermal growth factor signaling and mutation of the PTEN tumor suppressor. We further report the discovery of kinase inhibitors with selective toxicity to these groups. Overall, however, TNBC cell lines exhibited diverse sensitivity to kinase inhibition consistent with the lack of common driver mutations in this disease. While our findings support specific kinase dependencies in subsets of TNBC, they are not associated with gene expression-based subtypes. Instead we find that mutation status can be an effective predictor of sensitivity to inhibition of particular kinase pathways for subsets of TNBC. PMID:25344583

  4. ERα-Negative and Triple Negative Breast Cancer: Molecular Features and Potential Therapeutic Approaches

    PubMed Central

    Chen, Jin-Qiang; Russo, Jose

    2010-01-01

    Triple negative breast cancer (TNBC) is a type of aggressive breast cancer lacking the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER-2). TNBC patients account for approximately 15% of total breast cancer patients and are more prevalent among young African, African-American and Latino women patients. The currently available ER-targeted and Her-2-based therapies are not effective for treating TNBC. Recent studies have revealed a number of novel features of TNBC. In the present work, we comprehensively addressed these features and discussed potential therapeutic approaches based on these features for TNBC, with particular focus on: 1) the pathological features of TNBC/basal-like breast cancer; 2) E2/ERβ – mediated signaling pathways; 3) G-protein coupling receptor-30/epithelial growth factor receptor (GPCR-30/EGFR) signaling pathway; 4) interactions of ERβ with breast cancer 1/2 (BRCA1/2); 5) chemokine CXCL8 and related chemokines; 6) altered microRNA signatures and suppression of ERα expression/ERα-signaling by micro-RNAs; 7) altered expression of several pro-oncongenic and tumor suppressor proteins; and 8) genotoxic effects caused by oxidative estrogen metabolites. Gaining better insights into these molecular pathways in TNBC may lead to identification of novel biomarkers and targets for development of diagnostic and therapeutic approaches for prevention and treatment of TNBC. PMID:19527773

  5. Phototheranostics of CD44-positive cell populations in triple negative breast cancer.

    PubMed

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44(high)/CD24(low), and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC. PMID:27302409

  6. β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer.

    PubMed

    Yin, Hsin-Ling; Wu, Chun-Chieh; Lin, Chih-Hung; Chai, Chee-Yin; Hou, Ming-Feng; Chang, Shu-Jyuan; Tsai, Hung-Pei; Hung, Wen-Chun; Pan, Mei-Ren; Luo, Chi-Wen

    2016-01-01

    Triple negative breast cancer (TNBC) displays higher risk of recurrence and distant metastasis. Due to absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), TNBC lacks clinically established targeted therapies. Therefore, understanding of the mechanism underlying the aggressive behaviors of TNBC is required for the design of individualized strategies and the elongation of overall survival duration. Here, we supported a positive correlation between β1 integrin and malignant behaviors such as cell migration, invasion, and drug resistance. We found that silencing of β1 integrin inhibited cell migration, invasion, and increased the sensitivity to anti-cancer drug. In contrast, activation of β1 integrin increased cell migration, invasion, and decreased the sensitivity to anti-cancer drug. Furthermore, we found that silencing of β1 integrin abolished Focal adhesion kinese (FAK) mediated cell survival. Overexpression of FAK could restore cisplatin-induced apoptosis in β1 integrin-depleted cells. Consistent to in vitro data, β1 integrin expression was also positively correlated with FAK (p = 0.031) in clinical tissue. More importantly, β1 integrin expression was significantly correlated with patient outcome. In summary, our study indicated that β1 integrin could regulate TNBC cells migration, invasion, drug sensitivity, and be a potential prognostic biomarker in TNBC patient survival. PMID:27589736

  7. The Vacuolar ATPase a2-subunit regulates Notch signaling in triple-negative breast cancer cells

    PubMed Central

    Pamarthy, Sahithi; Jaiswal, Mukesh K.; Kulshreshtha, Arpita; Katara, Gajendra K.; Gilman-Sachs, Alice; Beaman, Kenneth D.

    2015-01-01

    Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer with poor prognosis for which no targeted therapies are currently available. Notch signaling has been implicated in breast cancer but the factors that control Notch in TNBC are unknown. Because the Vacuolar ATPase has been shown to be important in breast cancer invasiveness, we investigated the role of a2-subunit isoform of Vacuolar ATPase (a2V) in regulating Notch signaling in TNBC. Confocal microscopy revealed that among all the ‘a’ subunit isoforms, a2V was uniquely expressed on the plasma membrane of breast cancer cells. Both a2V and NOTCH1 were elevated in TNBC tumors tissues and cell lines. a2V knockdown by siRNA as well as V-ATPase inhibition by Bafilomycin A1 (Baf A1) in TNBC cell lines enhanced Notch signaling by increasing the expression of Notch1 intracellular Domain (N1ICD). V-ATPase inhibition blocked NICD degradation by disrupting autophagy and lysosomal acidification as demonstrated by accumulation of LC3B and diminished expression of LAMP1 respectively. Importantly, treatment with Baf A1 or anti-a2V, a novel-neutralizing antibody against a2V hindered cell migration of TNBC cells. Our findings indicate that a2V regulates Notch signaling through its role in endolysosomal acidification and emerges as a potential target for TNBC. PMID:26418877

  8. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth.

    PubMed

    Barbie, Thanh U; Alexe, Gabriela; Aref, Amir R; Li, Shunqiang; Zhu, Zehua; Zhang, Xiuli; Imamura, Yu; Thai, Tran C; Huang, Ying; Bowden, Michaela; Herndon, John; Cohoon, Travis J; Fleming, Timothy; Tamayo, Pablo; Mesirov, Jill P; Ogino, Shuji; Wong, Kwok-Kin; Ellis, Matthew J; Hahn, William C; Barbie, David A; Gillanders, William E

    2014-12-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible IκB kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK alone does not. CYT387 treatment inhibited activation of both NF-κB and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds. PMID:25365225

  9. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth

    PubMed Central

    Barbie, Thanh U.; Alexe, Gabriela; Aref, Amir R.; Li, Shunqiang; Zhu, Zehua; Zhang, Xiuli; Imamura, Yu; Thai, Tran C.; Huang, Ying; Bowden, Michaela; Herndon, John; Cohoon, Travis J.; Fleming, Timothy; Tamayo, Pablo; Mesirov, Jill P.; Ogino, Shuji; Wong, Kwok-Kin; Ellis, Matthew J.; Hahn, William C.; Barbie, David A.; Gillanders, William E.

    2014-01-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible IκB kinase–related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK alone does not. CYT387 treatment inhibited activation of both NF-κB and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds. PMID:25365225

  10. Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency.

    PubMed

    Jung, Hae Hyun; Lee, Soo-Hyeon; Kim, Ji-Yeon; Ahn, Jin Seok; Park, Yeon Hee; Im, Young-Hyuck

    2016-01-01

    We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfected DUSP4. We demonstrated that ETS1 mRNA and protein were overexpressed in TNBC cells compared with other BC cell lines (P = <0.001) and DUSP4 mRNA was downregulated (P = <0.001). MTT viability assay showed that simvastatin had significant antitumor activity (P = 0.002 in 0.1 μM). In addition, simvastatin could restore dusp4 deficiency and suppress ets-1 expression in TNBC. Lastly, we found that si-DUSP4 RNA transfection overcame the antitumor activity of statins. MAPK pathway inhibitor, U0126 and PI3KCA inhibitor LY294002 also decreased levels of ets-1, phosphor-ERK and phosphor-AKT on Western blot assay. Accordingly, our study indicates that simvastatin potentially affects the activity of transcriptional factors such as ets-1 and dusp4 through the MAPK pathway. In conclusion, statins might be potential candidates for TNBC therapy reducing ets-1 expression via overexpression of dusp4. PMID:27604655

  11. Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency

    PubMed Central

    Jung, Hae Hyun; Lee, Soo-Hyeon; Kim, Ji-Yeon; Ahn, Jin Seok; Park, Yeon Hee; Im, Young-Hyuck

    2016-01-01

    We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfected DUSP4. We demonstrated that ETS1 mRNA and protein were overexpressed in TNBC cells compared with other BC cell lines (P = <0.001) and DUSP4 mRNA was downregulated (P = <0.001). MTT viability assay showed that simvastatin had significant antitumor activity (P = 0.002 in 0.1 μM). In addition, simvastatin could restore dusp4 deficiency and suppress ets-1 expression in TNBC. Lastly, we found that si-DUSP4 RNA transfection overcame the antitumor activity of statins. MAPK pathway inhibitor, U0126 and PI3KCA inhibitor LY294002 also decreased levels of ets-1, phosphor-ERK and phosphor-AKT on Western blot assay. Accordingly, our study indicates that simvastatin potentially affects the activity of transcriptional factors such as ets-1 and dusp4 through the MAPK pathway. In conclusion, statins might be potential candidates for TNBC therapy reducing ets-1 expression via overexpression of dusp4. PMID:27604655

  12. A Distributed Network for Intensive Longitudinal Monitoring in Metastatic Triple-Negative Breast Cancer

    PubMed Central

    Blau, C. Anthony; Ramirez, Arturo B.; Blau, Sibel; Pritchard, Colin C.; Dorschner, Michael O.; Schmechel, Stephen C.; Martins, Timothy J.; Mahen, Elisabeth M.; Burton, Kimberly A.; Komashko, Vitalina M.; Radenbaugh, Amie J.; Dougherty, Katy; Thomas, Anju; Miller, Christopher P.; Annis, James; Fromm, Jonathan R.; Song, Chaozhong; Chang, Elizabeth; Howard, Kellie; Austin, Sharon; Schmidt, Rodney A.; Linenberger, Michael L.; Becker, Pamela S.; Senecal, Francis M.; Mecham, Brigham H.; Lee, Su-In; Madan, Anup; Ronen, Roy; Dutkowski, Janusz; Heimfeld, Shelly; Wood, Brent L.; Stilwell, Jackie L.; Kaldjian, Eric P.; Haussler, David; Zhu, Jingchun

    2016-01-01

    Accelerating cancer research is expected to require new types of clinical trials. This report describes the Intensive Trial of OMics in Cancer (ITOMIC) and a participant with triple-negative breast cancer metastatic to bone, who had markedly elevated circulating tumor cells (CTCs) that were monitored 48 times over 9 months. A total of 32 researchers from 14 institutions were engaged in the patient’s evaluation; 20 researchers had no prior involvement in patient care and 18 were recruited specifically for this patient. Whole-exome sequencing of 3 bone marrow samples demonstrated a novel ROS1 variant that was estimated to be present in most or all tumor cells. After an initial response to cisplatin, a hypothesis of crizotinib sensitivity was disproven. Leukapheresis followed by partial CTC enrichment allowed for the development of a differential high-throughput drug screen and demonstrated sensitivity to investigational BH3-mimetic inhibitors of BCL-2 that could not be tested in the patient because requests to the pharmaceutical sponsors were denied. The number and size of CTC clusters correlated with clinical status and eventually death. Focusing the expertise of a distributed network of investigators on an intensively monitored patient with cancer can generate high-resolution views of the natural history of cancer and suggest new opportunities for therapy. Optimization requires access to investigational drugs. PMID:26733551

  13. Angiotensin II-inhibition: effect on Alzheimer’s pathology in the aged triple transgenic mouse

    PubMed Central

    Ferrington, Linda; Palmer, Laura E.; Love, Seth; Horsburgh, Karen J; Kelly, Paul AT; Kehoe, Patrick G

    2012-01-01

    Reducing excessive accumulation of amyloid-β (Aβ) in Alzheimer's disease (AD) is a key objective of most AD therapies, and inhibition of angiotensin-converting enzyme (ACE) may delay onset or progression of AD. The effects of an ACE-inhibitor (ACE-I) and an angiotensin II receptor blocker (ARB) on Aβ and tau pathology in a triple transgenic (3xTGAD) mouse model of AD were investigated. 9-10month 3xTGAD mice were treated with ARB, ACE-I or vehicle for 6 months. Mean arterial blood pressure (MABP) was measured periodically and mice were assessed behaviourally. Aβ, phospho-tau, amyloid precursor protein (APP) and ACE activity were analysed. MABP was significantly reduced at 2 weeks and 3 months in the ACE-I group and at 3 months in the ARB group, compared to vehicle. Neither drug altered performance of 3xTGAD mice in Morris Water Maze or T-maze, nor were Aβ, tau immunolabelling or APP levels altered. ACE-I significantly reduced ACE activity in kidney. Prolonged treatment with ACE-I or ARB does not affect Aβ or phospho-tau accumulation in brains of aged 3xTGAD mice. PMID:22611468

  14. CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer.

    PubMed

    Paret, Claudia; Simon, Petra; Vormbrock, Kirsten; Bender, Christian; Kölsch, Anne; Breitkreuz, Andrea; Yildiz, Özlem; Omokoko, Tana; Hubich-Rau, Stefanie; Hartmann, Christoph; Häcker, Sabine; Wagner, Meike; Roldan, Diana Barea; Selmi, Abderaouf; Türeci, Özlem; Sahin, Ugur

    2015-09-22

    Triple-negative breast cancer (TNBC) is a high medical need disease with limited treatment options. CD8+ T cell-mediated immunotherapy may represent an attractive approach to address TNBC. The objectives of this study were to assess the expression of CXorf61 in TNBCs and healthy tissues and to evaluate its capability to induce T cell responses. We show by transcriptional profiling of a broad comprehensive set of normal human tissue that CXorf61 expression is strictly restricted to testis. 53% of TNBC patients express this antigen in at least 30% of their tumor cells. In CXorf61-negative breast cancer cell lines CXorf61 expression is activated by treatment with the hypomethylating agent 5-aza-2'-deoxycytidine. By vaccination of HLA-A*02-transgenic mice with CXorf61 encoding RNA we obtained high frequencies of CXorf61-specific T cells. Cloning and characterization of T cell receptors (TCRs) from responding T cells resulted in the identification of the two HLA-A*0201-restricted T cell epitopes CXorf6166-74 and CXorf6179-87. Furthermore, by in vitro priming of human CD8+ T cells derived from a healthy donor recognizing CXorf6166-74 we were able to induce a strong antigen-specific immune response and clone a human TCR recognizing this epitope. In summary, our data confirms this antigen as promising target for T cell based therapies. PMID:26327325

  15. CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer

    PubMed Central

    Paret, Claudia; Simon, Petra; Vormbrock, Kirsten; Bender, Christian; Kölsch, Anne; Breitkreuz, Andrea; Yildiz, Özlem; Omokoko, Tana; Hubich-Rau, Stefanie; Hartmann, Christoph; Häcker, Sabine; Wagner, Meike; Roldan, Diana Barea; Selmi, Abderaouf

    2015-01-01

    Triple-negative breast cancer (TNBC) is a high medical need disease with limited treatment options. CD8+ T cell-mediated immunotherapy may represent an attractive approach to address TNBC. The objectives of this study were to assess the expression of CXorf61 in TNBCs and healthy tissues and to evaluate its capability to induce T cell responses. We show by transcriptional profiling of a broad comprehensive set of normal human tissue that CXorf61 expression is strictly restricted to testis. 53% of TNBC patients express this antigen in at least 30% of their tumor cells. In CXorf61-negative breast cancer cell lines CXorf61 expression is activated by treatment with the hypomethylating agent 5-aza-2′-deoxycytidine. By vaccination of HLA-A*02-transgenic mice with CXorf61 encoding RNA we obtained high frequencies of CXorf61-specific T cells. Cloning and characterization of T cell receptors (TCRs) from responding T cells resulted in the identification of the two HLA-A*0201-restricted T cell epitopes CXorf6166–74 and CXorf6179–87. Furthermore, by in vitro priming of human CD8+ T cells derived from a healthy donor recognizing CXorf6166–74 we were able to induce a strong antigen-specific immune response and clone a human TCR recognizing this epitope. In summary, our data confirms this antigen as promising target for T cell based therapies. PMID:26327325

  16. Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5.

    PubMed

    D'Esposito, Vittoria; Liguoro, Domenico; Ambrosio, Maria Rosaria; Collina, Francesca; Cantile, Monica; Spinelli, Rosa; Raciti, Gregory Alexander; Miele, Claudia; Valentino, Rossella; Campiglia, Pietro; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Formisano, Pietro

    2016-04-26

    Growing evidence indicates that adiposity is associated with raised cancer incidence, morbidity and mortality. In a subset of tumors, cancer cell growth and/or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed, adipocytes represent the most abundant cell types surrounding breast cancer cells. We have studied the mechanisms by which peritumoral human adipose tissue contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and dissemination.Co-culture with human adipocytes enhanced MDA-MB231 cancer cell invasiveness. Adipocytes cultured in high glucose were 2-fold more active in promoting cell invasion and motility compared to those cultured in low glucose. This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5). Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte-induced breast cancer cell migration and invasion. CCL5 immuno-detection in peritumoral adipose tissue of women with TNBC correlated with lymph node (p-value = 0.04) and distant metastases (p-value = 0.001). A positive trend was also observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves showed a negative correlation between CCL5 staining in the peritumoral adipose tissue and overall survival of patients (p-value = 0.039).Thus, inhibition of CCL5 in adipose microenvironment may represent a novel approach for the therapy of highly malignant TNBC. PMID:27027351

  17. Response and resistance to BET bromodomain inhibitors in triple negative breast cancer

    PubMed Central

    Tabassum, Doris P.; Roberts, Justin M.; Janiszewska, Michalina; Huh, Sung Jin; Liang, Yi; Ryan, Jeremy; Doherty, Ernest; Mohammed, Hisham; Guo, Hao; Stover, Daniel G.; Ekram, Muhammad B.; Brown, Jonathan; D'Santos, Clive; Krop, Ian E.; Dillon, Deborah; McKeown, Michael; Ott, Christopher; Qi, Jun; Ni, Min; Rao, Prakash K.; Duarte, Melissa; Wu, Shwu-Yuan; Chiang, Cheng-Ming; Anders, Lars; Young, Richard A.; Winer, Eric; Letai, Antony; Barry, William T.; Carroll, Jason S.; Long, Henry; Brown, Myles; Liu, X. Shirley; Meyer, Clifford A.; Bradner, James E.; Polyak, Kornelia

    2015-01-01

    Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy1-3. BET bromodomain inhibitors, which have shown efficacy in several models of cancer4-6, have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyllysine recognition modules, leading to inhibition of oncogenic transcriptional programs7-9. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance. PMID:26735014

  18. Phototheranostics of CD44-positive cell populations in triple negative breast cancer

    PubMed Central

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M.

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44high/CD24low, and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC. PMID:27302409

  19. A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer

    PubMed Central

    Zeichner, Simon B.; Terawaki, Hiromi; Gogineni, Keerthi

    2016-01-01

    Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient’s treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC. PMID:27042088

  20. Targeting a cell state common to triple-negative breast cancers

    PubMed Central

    Muellner, Markus K; Mair, Barbara; Ibrahim, Yasir; Kerzendorfer, Claudia; Lechtermann, Hannelore; Trefzer, Claudia; Klepsch, Freya; Müller, André C; Leitner, Ernestine; Macho-Maschler, Sabine; Superti-Furga, Giulio; Bennett, Keiryn L; Baselga, José; Rix, Uwe; Kubicek, Stefan; Colinge, Jacques; Serra, Violeta; Nijman, Sebastian MB

    2015-01-01

    Some mutations in cancer cells can be exploited for therapeutic intervention. However, for many cancer subtypes, including triple-negative breast cancer (TNBC), no frequently recurring aberrations could be identified to make such an approach clinically feasible. Characterized by a highly heterogeneous mutational landscape with few common features, many TNBCs cluster together based on their ‘basal-like’ transcriptional profiles. We therefore hypothesized that targeting TNBC cells on a systems level by exploiting the transcriptional cell state might be a viable strategy to find novel therapies for this highly aggressive disease. We performed a large-scale chemical genetic screen and identified a group of compounds related to the drug PKC412 (midostaurin). PKC412 induced apoptosis in a subset of TNBC cells enriched for the basal-like subtype and inhibited tumor growth in vivo. We employed a multi-omics approach and computational modeling to address the mechanism of action and identified spleen tyrosine kinase (SYK) as a novel and unexpected target in TNBC. Quantitative phosphoproteomics revealed that SYK inhibition abrogates signaling to STAT3, explaining the selectivity for basal-like breast cancer cells. This non-oncogene addiction suggests that chemical SYK inhibition may be beneficial for a specific subset of TNBC patients and demonstrates that targeting cell states could be a viable strategy to discover novel treatment strategies. PMID:25699542