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Sample records for concurrent intra-arterial carboplatin

  1. Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy for gingival carcinoma

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    Mukai, Y.; Hata, M.; Koike, I.; Inoue, T. [Yokohama City University Graduate School of Medicine, Department of Radiology, Kanazawa-ku, Yokohama, Kanagawa (Japan); Mitsudo, K.; Koizumi, T.; Oguri, S.; Kioi, M.; Tohnai, I. [Yokohama City University Graduate School of Medicine, Department of Oral and Maxillofacial Surgery, Yokohama, Kanagawa (Japan); Omura, M. [Shonankamakura General Hospital, Department of Radiation Oncology, Kamakura, Kanagawa (Japan)

    2014-02-15

    The aim of this study was to review the efficacy and toxicity of radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy in the treatment of gingival carcinoma. In all, 34 patients (21 men and 13 women) with squamous cell carcinoma of the gingiva underwent radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy. Treatment consisted of daily external irradiation and concurrent retrograde superselective intra-arterial infusion with cisplatin and docetaxel. A median total dose of 60 Gy in 30 fractions was delivered to tumors. Of the 34 patients, 29 (85 %) achieved a complete response (CR) and 5 had residual tumors. Of the 29 patients with a CR, 2 had local recurrences and 1 had distant metastasis 1-15 months after treatment. Twenty-six of the 36 patients had survived at a median follow-up time of 36 months (range 12-79 months); 4 died of cancer and 4 died of non-cancer-related causes. At both 3 and 5 years after treatment, the overall survival rates were 79 % and the cause-specific survival rates were 85 %. Osteoradionecrosis of the mandibular bone only developed in 1 patient after treatment. Radiation therapy with concurrent retrograde superselective intra-arterial chemotherapy was effective and safe in the treatment of gingival carcinoma. This treatment may be a promising curative and organ-preserving treatment option for gingival carcinoma. (orig.) [German] Das Ziel dieser Studie war die Ueberpruefung der Effizienz und Toxizitaet einer Strahlenbehandlung des Gingivakarzinoms mit gleichzeitiger retrograder, superselektiver intraarterieller Chemotherapie. Insgesamt 34 Patienten (21 Maenner und 13 Frauen) mit Zahnfleischplattenzellkarzinom erhielten eine Strahlenbehandlung mit gleichzeitiger retrograder, superselektiver intraarterieller Chemotherapie. Die Behandlung umfasste eine taegliche externe Bestrahlung mit gleichzeitiger retrograder, superselektiver intraarterieller Infusion von Cisplatin und

  2. Intra-arterial administration of carboplatin plus lower dosage radiation of {sup 60}CO as induction treatment in advanced oral cancer

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    Okutomi, Tadashi; Kato, Yukihiro; Ichihara, Hideki; Kusunoki, Yukihiro; Hatakeyama, Daijiro; Yokoyama, Kyoko; Tatematsu, Norichika [Gifu Univ. (Japan). School of Medicine; Liu, Jianhua

    2000-11-01

    Conventional pre-operative chemoradiotherapy often causes severe side effects, which may result in interruption of the treatment and delay of decided operation. Carboplatin (CBDCA) is one of the effective chemotherapeutants for head and neck cancer. We treated 23 patients with advanced oral cancers by a combination of intra-arterial administration of Carboplatin and {sup 60}CO radiotherapy. The dosage of Carboplatin was between 20 mg and 35 mg per square meter of body surface. The dosage of external {sup 60}CO irradiation was 2 Gy per day and 30 to 60 Gy in total. We evaluated clinical response, toxicity and survival of this therapy of all the patients. Histologic response was also evaluated in some of them. All cancers responded to the regional chemoradiotherapy and demonstrated remission. Two (8%) completed response rate (CR) and 16 (69%) partial response rate (PR) were achieved. The accumulated five-year overall survival rate by Kaplan-Meier method was 73.9%. Fourteen patients (60.8%) showed no evidence of disease (NED) within five years after the therapy. All patients had stomatitis, but most of them were not so severe. The major hematological toxicity was leukopenia, but it was from mild to moderate and reversible. Our study showed that this therapy provided low toxicity, high clinical and histological response rate. (author)

  3. Intra-arterial cisplatin and concurrent radiation for invasive bladder cancer

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    Miyanaga, Naoto; Ohtani, Mikinobu; Noguchi, Ryosuke (Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine) (and others)

    1991-10-01

    Fifteen patients with invasive bladder cancer were treated with selective intra-arterial cisplatin and external beam radiotherapy (30.6 Gy over 3 weeks) prior to a planned cystectomy. Cisplatin, in total 200 mg, was administered via bilateral internal iliac artery infusion during the course of radiotherapy. Seven patients were evaluated for local response. Partial response (PR) was revealed in 4, and minor response (MR) in 3. Ten patients received total cystectomy, and pathological effects by the criteria adipted by Japanese Urological Association and The Japanese Society of Pathology, were as follows: Ef.3 in 1 case, Ef.2 in 6. Ef.1b in 1 and Ef.1a in 2. Down staging was observed in 8 patients from the clinical to the pathological stage. Thirteen patients are alive for 21 months. Two patients have died (1 lung infarction, 1 pancreatic cancer). Though nausea and sciatica-like pain were observed in some cases, there were no severe systemic side effects such as bone marrow suppression and renal toxicity. From these results it is concluded that this therapeutic modality could be effective in the preoperative work-up of candidates for total cystectomy, and also that it could be useful in the treatment of patients in whom total cystectomy is contraindicated. (author).

  4. Curative and organ-preserving treatment with intra-arterial carboplatin induction followed by surgery and/or radiotherapy for advanced head and neck cancer: single-center five-year results

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    Tinelli Carmine

    2007-04-01

    Full Text Available Abstract Background This study evaluated the feasibility, toxicity, response rate and survival of neoadjuvant superselective intra-arterial infusion of high dose carboplatin in advanced head and neck cancer. Methods Forty-six patients with primary head and neck squamous cell carcinoma received 3 cycles of intra-arterial carboplatin (300 to 350 mg/m2 per cycle every 2 weeks, followed by radiotherapy or surgery plus radiotherapy. Results No complications or severe toxicity occurred. Sixteen patients (35% were complete responders, 20 (43% partial responders while 10 (22% did not respond to treatment. After completion of the multimodality treatment, 38/46 patients (83% were complete responders. After a 5-year follow-up period, 18/46 patients (39% are alive and disease-free, 3 (6,5% have died of a second primary tumor and 25 (54,5% have died of the disease. Conclusion Intra-arterial carboplatin induction chemotherapy is a safe, well-tolerated technique that discriminates between responders and non-responders and so may have prognostic significance in planning further integrated treatments aimed to organ preservation for advanced head and neck carcinomas.

  5. Paclitaxel and carboplatin concurrent with radiotherapy for primary cervical cancer

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    De Vos, FYFL; Bos, AME; Gietema, JA; Pras, E; Van Der Zee, AGJ; De Vries, EGE; Willemse, PHB

    2004-01-01

    Background: Concurrent radiochemotherapy is currently considered the new standard treatment in locally advanced cervical cancer. Patients and Methods: Eight women with cervical cancer stage IB2-IVA were treated with standard radiation therapy in combination with standard carboplatin (AUC=2, once wee

  6. Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: A p

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil.RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) mo. One patient showed complete response (CR) with disappearance of HCC and PVTT after treatment, and the two patients showed partialresponse (PR), response rate (CR + PR/All cases 30%).The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.

  7. Chemotherapy using new superselective intra-arterial infusion for advanced oral cancer

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    Iwai Tohnai; Kenji Mitsudo; Takefumi Fukui; Toshinori Iwai; Kei Watanuki; Yoshiro Matsui

    2008-01-01

    @@ Purpose: We developed a new method of superselective intra-arterial infusion via the superficial temporal artery (HFT method: Hattori, Fuwa and Tohnai reported) and preoperatively performed daily concurrent radiotherapy and chemotherapy with docetaxel (DOC) and cisplatin (CDDP) using this method for 46 patients with stage Ⅲ, Ⅳ oral cancer.

  8. Clinical Outcome in Definitive Concurrent Chemoradiation With Weekly Paclitaxel and Carboplatin for Locally Advanced Esophageal and Junctional Cancer.

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    Noronha, Vanita; Prabhash, Kumar; Joshi, Amit; Patil, Vijay Maruti; Talole, Sanjay; Nakti, Dipti; Sahu, Arvind; Shah, Srushti; Ghosh-Laskar, Sarbani; Patil, Prachi S; Mehta, Shaesta A; Jambhekar, Nirmala; Mahajan, Abhishek; Purandare, Nilendu

    2016-01-01

    There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m(2) and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8-13.9), median OS was 19 months (95% CI: 15.4-22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel-carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.].

  9. Intra-arterial chemotherapy in combination with radiotherapy for invasive bladder cancer and prostate cancer

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    Sumiyoshi, Yoshiteru; Hashine, Katsuyoshi; Nakatsuji, Hiroyoshi [National Shikoku Cancer Center Hospital, Matsuyama (Japan)

    1999-02-01

    Forty-five patients with muscle-invasive bladder cancer treated with intra-arterial doxorubicin chemotherapy plus low-dose radiotherapy between September 1979 and March 1990 were retrospectively studied. Twenty-eight (62%) patients achieved a complete response (CR) and in all of them, a functional bladder could be preserved. The 10-year cause-specific survival rate of patients with CR was 95.5%, but that of patients not achieving a CR was 39%. These results demonstrate that in patients who achieve a CR with this treatment, we may be able to preserve a functional bladder. In a prospective study, we designed a new intra-arterial chemotherapy regimen in order to achieve a higher degree of effectiveness and to preserve a functional bladder. Twenty-three patients were treated with concurrent pirarubicin/cisplatin intra-arterial chemotherapy and radiotherapy after complete transurethral resection. Twenty-one (91%) patients achieved CR. One of these patients had relapse with lung metastases and was treated surgically. Two patients who did not achieve a CR died of cancer, and 21 patients are alive with preservation of functional bladder. For treatment of prostate cancer, we now administer only adjuvant intra-arterial chemotherapy plus irradiation for patients after radical prostatectomy. (author)

  10. Continuous-Course Reirradiation With Concurrent Carboplatin and Paclitaxel for Locally Recurrent, Nonmetastatic Squamous Cell Carcinoma of the Head-and-Neck

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    Kharofa, Jordan [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Choong, Nicholas [Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Wang, Dian; Firat, Selim; Schultz, Christopher [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Sadasiwan, Chitra [Medical College of Wisconsin, Milwaukee, WI (United States); Wong, Stuart, E-mail: Swong@mcw.edu [Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

    2012-06-01

    Purpose: To examine the efficacy and toxicity of continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin for the treatment of locally recurrent, nonmetastatic squamous cell carcinoma of the head and neck (SCCHN) in a previously irradiated field. Methods and Materials: Patients treated with continuous course-reirradiation with concurrent carboplatin and paclitaxel at the Medical College of Wisconsin and the Clement J. Zablocki VA from 2001 through 2009 were retrospectively reviewed. Patients included in the analysis had prior radiation at the site of recurrence of at least 45 Gy. The analysis included patients who received either intensity-modulated radiotherapy (RT) or three-dimensional conformal RT techniques. All patients received weekly concurrent carboplatin (AUC2) and paclitaxel (30-50 mg/m{sup 2}). Results: Thirty-eight patients with nonmetastatic SCCHN met the entry criteria for analysis. The primary sites at initial diagnosis were oropharyngeal or laryngeal in most patients (66%). Median reirradiation dose was 60 Gy (range, 54-70 Gy). Acute toxicity included Grade 2 neutropenia (5%), Grade 3 neutropenia (15%), and Grade 1/2 thrombocytopenia (8%). No deaths occurred from hematologic toxicity. Chemotherapy doses held (50%) was more prevalent than radiation treatment break (8%). Sixty-eight percent of patients required a gastrostomy tube in follow-up. Significant late toxicity was experienced in 6 patients (16%): 1 tracheoesophageal fistula, 1 pharyngocutaneous fistula, 3 with osteoradionecrosis, and 1 patient with a lingual artery bleed. Patients treated with three-dimensional conformal RT had more frequent significant late toxicites than patients treated with intensity-modulated RT (44% and 7% respectively, p < 0.05). The median time to progression was 7 months and progression-free rates at 1, 2, and 5 years was 44%, 34%, and 29% respectively. The median overall survival was 16 months. Overall survival at 1, 3, and 5 years was 54

  11. INTRA-ARTERIAL PREOPERATIVE CHEMOTHERAPY FOR LOCALLY ADVANCED BREAST CANCER

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    A. D. Zikiryakhodzhaev

    2015-01-01

    Full Text Available Abstract:The article is devoted to studying the prospects of the use of selective intra-arterial chemotherapy in the treatment of locally advanced breast cancer IIIA, B, C stages. A review of literature on the methods of targent intra-arterial infusion of cytostatics and tumor embolization is performed, also it shows the results of treatment with different chemotherapeutic agents — epirubicin, doxorubicin, taxotere, cisplatin, 5‑fluorouracil, cyclophosphamide.

  12. CT angiography by means of intra-arterial contrast infusion

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    Okada, Junichiro; Watanabe, Hiroshi; Shiogai, Toshiyuki; Konishi, Yoshifumi; Hara, Mitsuhiro (Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine)

    1983-10-01

    CT angiography (CT-AG) by means of intra-arterial contrast infusion was carried out, and its clinical usefulness was evaluated in various intracranial lesions. The practical and diagnostic merits of CT-AG are as follows: a selective enhancement of the cerebral vessels by an extremely small amount of the contrast substance, accompanied by a satisfactory resolution of fine arterioles and arteries. The excellent ability of the CT to detect differences in the X-ray absorption coefficients surpasses that of cerebral angiography. An intracranial aneurysm which was not visualized by the angiography appeared between arterial branches upon CT-AG. The three-dimensional configuration of the aneurysmal body and its related artery, the pointing direction of the aneurysm, and the angle between the aneurysmal axis and the afferent artery were clearly shown. The fine structure of arteriovenous malformation could be shown concurrently with the cerebral tissue and the ventricle. The axial view of the circle of Willis gives important information for surgical intervention. Concerning brain tumors, the structural correlation between the tumor and the cerebral arteries became apparent when the CT-AG was carried out immediately after a conventional contrast-enhancement. Such a ''double contrast'' allows safe surgical access to the intracranial tumor. CT-AG in the case of ''Moyamoya'' disease visualized fine moyamoya vessels extending all over the cerebral hemisphere; those vessels were less prominent in the ordinary angiograms. The vascular networks of the arteriovenous malformation, which were not evident in the ordinary angiograms, were also revealed by the CT-AG. For the patient with poor prospects, CT-AG will be were valid as a screening study than ordinary angiography because of its less invasive procedure using a small amount of the contrast substance. CT-AG on a dynamic scan mode possible optimal timing in the visualization of the

  13. Intra-arterial injection of Tc-99m MDP

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    Ebru Salmanoglu

    2016-03-01

    Full Text Available Bone scintigraphy is applied to evaluate abnormalities of axial skeleton and appendicular skeleton including osteomyelitis, prosthesis infection, prosthesis loosening, avascular necrosis, stress fracture, bone metastasis. Technetium-99m methylene diphosphonate (Tc-99m MDP is most common used radiopharmaceutical. Injection of Tc-99m MDP should be done intravenous but it can be done intra-arterial, accidentally. After intra-arterial injection of Tc-99m MDP, it cause prominent soft tissue uptake distal to the injection site. This situation can create confusion in the scintigraphic images. Usually, it imitate reflex sympathetic dystrophy, so differential diagnosis is important. The aim of this report is to present the appearance of inadvertent intra-arterial injection of Tc-99m MDP. [Cukurova Med J 2016; 41(0.100: 79-82

  14. Clinical efficacy of concurrent carboplatin, etoposide, and definitive radiotherapy for stage III non-small-cell lung cancer. Consideration as to therapeutic outcomes and morbidity

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    Kodaira, Takeshi; Yamakawa, Kouji; Taniguchi, Hiroyuki [Tosei General Hospital, Seto, Aichi (Japan); Matsubara, Kazuhito; Ishigaki, Takeo

    1998-08-01

    To improve the therapeutic outcome for inoperable non-small-cell lung cancer, we applied definitive thoracic radiotherapy combined with concurrent administration of carboplatin and etoposide. We retrospectively analyzed 55 eligible patients with Stage III disease. The one-year rate of overall survival (OAS) and distant metastasis-free survival (DMFS) of the total group were 46.1% and 36.1%, respectively. Twenty-nine patients developed thoracic failures (52.7%) and 23 (41.8%) distant failures. Using univariate and multivariate analyses, radiation dose, performance status and LDH were revealed as significant prognostic factors of OAS, and LDH had a strong adverse effect on DMFS. Leucopenia of Grade 3 or higher was noted in 75.9%, anemia in 55.6%, thrombocytopenia in 59.3%, esophagitis in 20.4%, and lung injury in 10.9%. Sufficient gain was not obtained by out strategy, and higher morbidity, especially of lung, was noted than was expected. It was suspected that simultaneous use of oral etoposide might increase radiation pneumonitis, so one should take special care of unexpected toxicity in concurrent chemoradiotherapy. Both the hyperfractionated technique of radiotherapy and the time-dose modification of anti-tumor drugs should be considered in further steps. (author)

  15. Induction chemotherapy with carboplatin-paclitaxel followed by standard radiotherapy with concurrent daily low-dose cisplatin plus weekly paclitaxel for inoperable non-small-cell lung cancer.

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    Ardizzoni, Andrea; Scolaro, Tindaro; Mereu, Carlo; Cafferata, Mara Argenide; Tixi, Lucia; Bacigalupo, Almalina; Tiseo, Marcello; Monetti, Francesco; Rosso, Riccardo

    2005-02-01

    Both induction chemotherapy and concurrent platinating agents have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study investigated activity and feasibility of a novel chemoradiation regimen, including platinum and paclitaxel, both as induction chemotherapy and concurrently with thoracic radiotherapy. Previously untreated patients with histologically/cytologically proven unresectable stage I-III NSCLC were eligible. Induction chemotherapy consisted of 2 courses of 200 mg/m2 paclitaxel and carboplatin at AUC of 6 mg/mL/min every 3 weeks. From day 43, continuous thoracic irradiation (60 Gy in 30 fractions radiotherapy for 6 weeks) was given concurrently with daily cisplatin at a dose of 5 mg/m2 intravenously and weekly paclitaxel at a dose of 45 mg/m2 for 6 weeks. Fifteen patients were accrued in the first stage of the trial. According to the previous statistical considerations, accrual at the second stage of the study was halted as a result of the achievement an insufficient number of successes. Major toxicity of combined chemoradiation was grade III-IV esophagitis requiring hospitalization for artificial nutrition, which occurred in 58% of patients. Other toxicities included grade II-IV fatigue in 75% of patients and grade I-IV neuromuscular toxicity in 67%. Only 7 patients completed the treatment program as scheduled. Eight patients (53.3%; 95% confidence interval, 26.5-78.7%) had a major response (5 partial response, 3 complete response), 2 patients had disease progression, and 1 was stable at the end of treatment. Four patients died early. With a median follow up of 38 months, the median survival was 12 months. A combined chemoradiation program, including platinum and paclitaxel, appears difficult to deliver at full dose as a result of toxicity, mainly esophagitis. More active and less toxic combined modality treatments need to be developed for inoperable NSCLC.

  16. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

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    Tan, Terence, E-mail: trdtwk@nccs.com.sg [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Lim, Wan-Teck [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Ong, Whee-Sze; Tan, Sze-Huey [Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore (Singapore); Yip, Connie; Quah, Daniel [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Soo, Khee-Chee [Division of Surgical Oncology, National Cancer Centre Singapore (Singapore); Wee, Joseph [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore)

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  17. Intra-Arterial Treatment of Primary and Metastatic Liver Tumors

    NARCIS (Netherlands)

    Buijs, M.A.M.; Vossen, J.A.

    2009-01-01

    The aims of this thesis were, first, to investigate the toxicities associated with trans-arterial chemoembolization (TACE) of liver tumors and to evaluate the use of MR imaging in characterizing tumor response after this locoregional therapy, second, to further develop intra-arterial therapy of live

  18. Intra-arterial nimodipine for cerebral vasospasm after subarachnoid haemorrhage

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    Bashir, Asma; Andresen, Morten; Bartek, Jiri

    2016-01-01

    Intra-arterial nimodipine (IAN) has shown a promising effect on cerebral vasospasm (CV) after aneurysmal subarachnoid haemorrhage. At our institution, Rigshospitalet, IAN treatment has been used since 2009, but the short- and long-term clinical efficacy of IAN has not yet been assessed. The purpose...

  19. Simultaneous Integrated Boost Using Intensity-Modulated Radiotherapy Compared With Conventional Radiotherapy in Patients Treated With Concurrent Carboplatin and 5-Fluorouracil for Locally Advanced Oropharyngeal Carcinoma

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    Clavel, Sebastien, E-mail: sebastien.clavel@umontreal.ca [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen, David H.A.; Fortin, Bernard [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Despres, Philippe [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Khaouam, Nader [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Donath, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Soulieres, Denis [Department of Medical Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Guertin, Louis [Department of Head and Neck Surgery, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen-Tan, Phuc Felix [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada)

    2012-02-01

    Purpose: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. Methods and Materials: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. Results: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. Conclusions: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.

  20. Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel or cisplatin/etoposide in stage III non-small cell lung cancer.

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    Liew, Mun Sem; Sia, Joseph; Starmans, Maud H W; Tafreshi, Ali; Harris, Sam; Feigen, Malcolm; White, Shane; Zimet, Allan; Lambin, Philippe; Boutros, Paul C; Mitchell, Paul; John, Thomas

    2013-12-01

    Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each with concurrent radiotherapy, remain largely undefined. Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60 Gy chest radiotherapy between 2000 and 2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student's t and chi-squared tests. Seventy-five (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs. 63 years; P = 0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs. 14%, P = 0.024) and thrombocytopenia (10% vs. 0%, P = 0.039). Radiation pneumonitis was more common with PC (66% vs. 38%, P = 0.033). Five treatment-related deaths occurred (PC: 3 vs. PE: 2, P = 1.000). With a median follow-up of 51.6 months, there were no significant differences in relapse-free survival (median PC 12.0 vs. PE 11.5 months, P = 0.700) or overall survival (median PC 20.7 vs. PE 13.7 months; P = 0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities.

  1. Differential routes of carboplatin administration influence lymphocyte apoptosis in retroperitoneal lymph nodes.

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    Huang, Yong-Wen; Zeng, Zheng; Li, Su; Liu, Ji-Hong

    2012-12-01

    We aimed to investigate carboplatin distribution in retroperitoneal lymph nodes and its effect on lymphocyte apoptosis following intravenous (IV), intra-arterial (IA), and retroperitoneal (RP) administration. Sixty-three healthy female canines were randomly assigned as IV, IA, or RP administration of carboplatin. At 0.5, 1, 2, 4, 8, 24, and 72 h after carboplatin treatment, retroperitoneal lymph nodes (n = 6 at each time point) were collected and high-performance liquid chromatography was employed to measure the carboplatin content. The differences in carboplatin pharmacokinetics of the three administration routes were compared. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) was carried out to measure the lymphocyte apoptosis of the retroperitoneal lymphocytes. The peak concentration of carboplatin in plasma following IV administration was the highest among all approaches; as to the peak time, RP administration was longer than the other two administrations. Concentration for carboplatin in the retroperitoneal lymph node was highest following IA administration at early time points, but at higher time points, concentration was significantly higher following RP administration. Penetration of carboplatin into the retroperitoneal space was higher following RP administration. Following RP administration, the level of apoptotic lymphocytes in the retroperitoneal lymph nodes was significantly greater than either IV or IA. Following RP administration of carboplatin, the concentration, area under the curve of carboplatin and the number of apoptotic lymphocytes were significantly higher than those following IV and IA administration. This suggests that RP administration of carboplatin is beneficial for the treatment of retroperitoneal lymph node metastasis.

  2. [Maxillary Cancer with Metastasis to the Rouviere Nodes -- Complete Response to Chemoradiotherapy Using a Selective Intra-Arterial Infusion Technique].

    Science.gov (United States)

    Yamashiro, Keita; Heianna, Joichi; Azama, Kimei; Iraha, Yuko; Yamashiro, Tsuneo; Kinoshita, Ryo; Toita, Takafumi; Toyama, Masatomo; Agena, Shinya; Maeda, Hiroyuki; Suzuki, Mikio; Murayama, Sadayuki

    2016-02-01

    We report a case of advanced maxillary cancer with multiple lymph node metastases, including metastasis to the Rouviere nodes, which were successfully treated with chemoradiotherapy using a selective intra-arterial infusion technique.A 71-yearold man presented to our hospital with complaints of a staggering gait and epistaxis.He was diagnosed with maxillary cancer (squamous cell carcinoma)classified as T4a disease.Because multiple lymph node metastases were detected, including metastasis to the Rouviere nodes, radical surgical treatment was considered inadequate.Thus, the patient was treated with concurrent chemoradiotherapy with selective intra-arterial infusion of nedaplatin and docetaxel.After chemoradiotherapy, the maxillary cancer and lymph metastasis nearly resolved and the patient achieved a complete response.No additional surgery was needed, and the patient was discharged.We suggest that chemoradiotherapy using a selective intra-arterial infusion technique is a highly effective treatment option for patients with maxillary cancer and metastasis to the Rouviere nodes.

  3. Update on Intra-Arterial Chemotherapy for Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Mario Zanaty

    2014-01-01

    Full Text Available The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

  4. [Intra-arterial thrombolysis of acute mesenteric ischemia].

    Science.gov (United States)

    Nathan, N; Wintringer, P; Bregeon, Y; Cassat, C; Le Blanche, A; Boulanger, J P; Feiss, P

    1995-01-01

    A 73-year-old man with pre-existing cardiac failure, coronary artery and chronic obstructive pulmonary disease was presented for an acute mesenteric ischaemia, resulting from an embolic obstruction of the superior mesenteric artery. An intra-arterial fibrinolysis with a bolus of 250 000 units of streptokinase, followed by an infusion of 150 mg rtPA with adequate heparin dosage was performed 10 hours after the first symptoms. An abdominal guarding occurred 24 hours later, despite radiological improvement, justifying emergency surgery which confirmed the partial efficiency of the medical therapy. Unfortunately, a cardiogenic shock occurred preoperatively and the patient died five days later from intractable cardiovascular failure.

  5. Continuous intra-arterial blood-gas monitoring

    Science.gov (United States)

    Divers, George A.; Riccitelli, Samuel D.; Blais, Maurice; Hui, Henry K.

    1993-05-01

    Fiber optic technology and optical fluorescence have made the continuous monitoring of arterial blood gases a reality. Practical products that continuously monitor blood gases by use of an invasive sensor are now available. Anesthesiologists and intensive care physicians are beginning to explore the practical implications of this technology. With the advent of intra- arterial blood gas monitors it is possible to assess arterial blood gas values without the labor intensive steps of drawing blood and transporting a blood sample to the lab followed by the actual analysis. These intra-arterial blood gas monitors use new optical sensor technologies that can be reduced in size to the point that the sensor can be inserted into the arterial blood flow through a 20-gauge arterial cannula. In the best of these technologies the sensors accuracy and precision are similar to those in vitro analyzers. This presentation focuses on background technology and in vivo performance of a device developed, manufactured, and marketed by Puritan-Bennett Corporation.

  6. Percutaneous intra-arterial chemotherapy of osteosarcoma with cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Duk; Byun, Hong Sik; Kim, Kie Hwan; Chin, Soo Yil; Chung, Jin Youb; Lee, Soo Yong [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1990-04-15

    Intra-arterial Chemotherapy (IAC) was performed to the 34 patients with non metastatic osteosarcoma using Cisplatin and surgery was done in 26 cases out of 34. We analysed the therapeutic effect of IAC in the view of local control rate and distant metastasis for two and half years. Local control rate was 94% on the base of the radiologic studies including simple X-ray, angiography and CT. No variable cells were observed in 50% of the cases on the pathologic examination of the surgical specimens. Distant metastasis developed in 14 cases (41%), mainly in the lung. No significant complications occurred except each case of acute renal failure, congestive heart failure and peripheral embolism, which were improved by proper management. IAC is one of the most effective methods in controlling the regionally confined osteosarcoma, but it may be incorporated with other adjuvant protocols to decrease the chance of delayed metastasis.

  7. Gas gangrene following intra-arterial injection of oral medication in a drug abuser.

    Science.gov (United States)

    Haiart, D C; Andrade, B; Murie, J A

    1992-09-01

    We report a patient in whom intra-arterial injection of oral medication led to the development of fulminating gas gangrene and death, despite the initial clinical symptoms being minor. We believe that prophylactic antibiotics should be administered to patients following intra-arterial injection of oral medication especially if immunocompetence, such as from human immunodeficiency virus (HIV) infection, is likely.

  8. Spontaneously resolving periocular erythema and ciliary madarosis following intra-arterial chemotherapy for retinoblastoma

    Directory of Open Access Journals (Sweden)

    Marr Brian

    2010-01-01

    Full Text Available Purpose and Design: To describe an unusual clinical finding seen in children undergoing intra-arterial chemotherapy for retinoblastoma. Materials and Methods: A retrospective review of 69 eyes of 63 patients receiving intra-arterial chemotherapy over a 3-year period. Charts and photographs of 69 consecutive cases were reviewed, and data were collected on patients with clinical evidence of a hyperemic cutaneous periocular abnormality following the procedure. Results: A blanching erythematous and edematous patch was noted in the periocular region in 16% (11 of 69 of the children who received intraarterial chemotherapy. The plaque extended into the region of the supertrochlear and medial marginal artery distribution on the ipsilateral side of the intra-arterial chemotherapy. All patches of erythema spontaneously resolved within 3 months following completion of the intra-arterial chemotherapy. Conclusion: Periocular erythema and swelling is a self-limited clinical finding associated with intra-arterial chemotherapy in a small number of patients.

  9. Are intravenous injections of contrast media really less nephrotoxic than intra-arterial injections?

    Energy Technology Data Exchange (ETDEWEB)

    Nyman, Ulf [University of Lund, Department of Diagnostic Radiology, Trelleborg (Sweden); Almen, Torsten [Skaane University Hospital, Department of Clinical Sciences/Medical Radiology, University of Lund, Malmoe (Sweden); Jacobsson, Bo [University of Gothenburg and the Sahlgrenska Academy, Department of Diagnostic Radiology, The Queen Silvia Children' s Hospital, Goeteborg (Sweden); Aspelin, Peter [Karolinska Institute and University Hospital, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden)

    2012-06-15

    We oppose the opinion that the intra-arterial administration of iodine-based contrast media (CM) appears to pose a greater risk of contrast medium-induced nephropathy (CIN) than intravenous administration since (1) in intra-arterial coronary procedures and most other intra-arterial angiographic examinations, CM injections are also intravenous relative to the kidneys, (2) there is a lack of comparative trials studying the risk of CIN between intra-arterial and intravenous procedures with matched risk factors and CM doses, (3) a bias selection of patients with fewer risk factors may explain the seemingly lower rate of CIN after CT in comparison with coronary interventions, (4) the rate of CIN following intra-arterial coronary procedures may also be exaggerated owing to other causes of acute kidney failure, such as haemodynamic instability and microembolisation, (5) roughly the same gram-iodine/GFR ratio ({approx}1:1) as a limit of relatively safe CM doses has preliminarily been found for both intravenous CT and intra-arterial coronary procedures and (6) the substantially higher injected intravenous CM dose rate during CT relative to an intra-arterial coronary procedure might actually pose a higher risk of CIN following CT. Key Points circle Most intra-arterial injections of contrast media are intravenous relative to the kidneys. circle No evidence that intravenous CM injections should be less nephrotoxic than intra-arterial. circle Considerably higher dose rates of CM are used for CT relative to intra-arterial procedures. circle Higher dose rates may pose higher nephrotoxic risk for intravenous based CT studies. (orig.)

  10. Intra-arterial delivery of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Mitsuyoshi Watanabe

    2016-01-01

    Full Text Available While treatments have been developed to combat stroke, such as intravenous recombinant tissue plasminogen activator and endovascular recanalization therapies, their ability to decrease the long-term disability that accompanies stroke is limited. Currently, stem cell research focused on mesenchymal stem cells (MSCs. MSCs are multipotent, nonhematopoietic stem cells found in the stromal fraction of the bone marrow, along with the connective tissue of most organs. MSCs are an increasingly appealing cell source due to the relative ease in which they can be retrieved, developed, and handled in vitro. Despite the fact that numerous paths of stem cell transport to the brain in acute ischemic stroke (AIS exist, the intra-arterial (IA route of stem cell transport is most attractive. This is due to its great potential for clinical translation, especially considering the growing clinical application of endovascular treatment for AIS. Here, we evaluate research examining IA delivery of MSCs to the stroke region. The results of the study revealed the maximum tolerated dose and that the optimal time for administration was 24 h, following cerebral ischemia. It is important that future translational studies are performed to establish IA administration of MSCs as a widely used treatment for AIS.

  11. Intra-arterial chemotherapy for retinoblastoma: First Indian report

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2015-01-01

    Full Text Available Aim: To describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC for retinoblastoma (RB in Indian eyes. Materials and Methods: Single center, retrospective interventional case series of 6 eyes with RB who underwent IAC using Melphalan (3 mg/5 mg/7.5 mg and topetecan (1 mg (n = 4 or melphalan (3 mg/5 mg/7.5 mg alone (n = 2 between December 2013 and June 2014. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seeds control and globe salvage rates. Results: IAC was employed as primary (n = 1 or secondary (n = 5 modality of treatment. Each eye received mean 3 IAC sessions (median: 3; range: 1-4 sessions. Eyes were classified according to international classification of RB as Group B (n = 1, C (n = 1, D (n = 2 and E (n = 2. Following IAC, complete regression of the main tumor was seen in 3 cases (50%, partial regression in 2 (33%, while 1 case (15% showed no response. Of 4 eyes with subretinal seeds, 1 (25% eye had complete regression while 3 (75% eyes had partial regression. Of 5 eyes with vitreous seeds, 2 (40% eyes had complete regression while 3 (60% eyes had a partial response. Globe salvage was achieved in 5 of 6 eyes (83%. Diffuse choroidal atrophy and vitreous hemorrhage were observed in 1 (17% eye, each. No hematologic toxicity or cerebro-vascular events were observed. Mean follow-up period was 5.5 months (median: 6 months, range: 1-6 months. Conclusion: IAC is an effective therapy for globe preservation in eyes with RB. Larger studies with longer follow-up are required to validate these results.

  12. Intra-Arterial Thrombolysis for Deep Vein Thrombosis of the Lower Extremity: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moo Sang; Roh, Byung Suk [Dept. of Radiology, Wonkwang University School of Medicine, Iksan (Korea, Republic of)

    2011-09-15

    If the appropriate catheterization of the affected vein was not possible because of a narrowed or thrombus-filled venous lumen, successful treatment gets into trouble during catheter directed regional thrombolysis for treatment of deep vein thrombosis. In this situation, intra-arterial thrombolysis can be considered as an alternative treatment, but to the best of our knowledge, only two reports have been described. We present here cases of successful intra-arterial thrombolysis in patients with deep vein thrombosis.

  13. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  14. Feasibility, toxicity, and efficacy of short induction chemotherapy of docetaxel plus cisplatin or carboplatin (TP) followed by concurrent chemoradiotherapy for organ preservation in advanced cancer of the hypopharynx, larynx, and base of tongue. Early results

    Energy Technology Data Exchange (ETDEWEB)

    Semrau, Sabine; Klautke, Gunther; Fietkau, Rainer [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Waldfahrer, Frank; Iro, Heinrich [Erlangen-Nuernberg Univ., Erlangen (Germany). Hals-Nasen-Ohrenklinik, Kopf- und Halschirurgie; Lell, Michael; Uder, Michael [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Radiologie; Linke, Rainer; Kuwert, Torsten [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. und Poliklinik fuer Nuklearmedizin

    2011-01-15

    Concurrent chemoradiotherapy (CRT) is standard treatment for advanced head and neck cancer. Whether short induction chemotherapy (ICT) provides additional benefit or, in particular, predictive benefit for the response to chemoradiotherapy is an open question. The present study aimed to assess the feasibility, toxicity, and efficacy of induction with docetaxel and platinum salt (TP) and subsequent CRT. A total of 25 patients with functionally inoperable cancer of the base of the tongue, hypopharynx, or larynx received 1 cycle of docetaxel (75 mg/m{sup 2}, day 1) combined with either cisplatin (30 mg/m{sup 2}, days 1-3; n = 23) or carboplatin (AUC 1.5 days 1-3; n = 2). Responders (n = 22, > 30% tumor reduction, graded by endoscopy) and 1 non-responder received CRT (target dose: 69-72 Gy) with cisplatin/paclitaxel, carboplatin/paclitaxel, or cisplatin/docetaxel. All patients completed ICT with acceptable toxicity (leukocytopenia grade 4: 8%). The remission rate of the primary tumor was 88% (22/25 patients). There was no need to delay CRT due to toxicity in any case. Each patient received the full radiation dose. Of the patients, 56% received > 80% of the chemotherapy. The acute toxicity of CRT was moderate, no grade 4 toxicities occurred, while grade 3 toxicities included the following: infection (39%), dermatitis (13%), leukocytopenia (30%), and thrombocytopenia (4%). The local control rate was 84.6% {+-} 8.5% and the survival rate was 89.6% {+-} 7.2% at 12 months. Organ preservation was possible in 22/23 (95%) cases. Short induction with a TP regimen and subsequent CRT with a taxan is feasible and associated with an encouraging local control rate. (orig.)

  15. Phase II Study Evaluating the Addition of Cetuximab to the Concurrent Delivery of Weekly Carboplatin, Paclitaxel, and Daily Radiotherapy for Patients With Locally Advanced Squamous Cell Carcinomas of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Suntharalingam, Mohan, E-mail: msuntha@umm.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Kwok, Young [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Goloubeva, Olga [University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD (United States); Parekh, Arti [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Taylor, Rodney; Wolf, Jeffrey [Department of Otorhinolaryngology, University of Maryland School of Medicine, Baltimore, MD (United States); Zimrin, Ann [University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD (United States); Strome, Scott [Department of Otorhinolaryngology, University of Maryland School of Medicine, Baltimore, MD (United States); Ord, Robert [Department of Oral-Maxillo Facial Surgery, University of Maryland School of Medicine, Baltimore, MD (United States); Cullen, Kevin J. [University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD (United States)

    2012-04-01

    Purpose: To report the mature data of a prospective Phase II trial designed to evaluate the efficacy of an epidermal growth factor receptor inhibitor cetuximab (CTX) added to the concurrent therapy of weekly paclitaxel/carboplatin (PC) and daily radiation therapy (RT). Methods and Materials: From 2005 to 2009, a total of 43 patients were enrolled in the study. The median follow-up was 31 months (range, 9-59 months). All patients had Stage III/IV disease at presentation, and 67% had oropharyngeal primaries. The weekly IV dose schedules were CTX 250 mg/m{sup 2} (400 mg/m{sup 2} IV loading dose 1 week before RT), paclitaxel 40 mg/m{sup 2}, and carboplatin AUC 2. RT was given at 1.8 Gy per day to 70.2 Gy. Intensity-modulated RTwas used in 70% of cases. Results: All patients completed the planned RT dose, 74% without any treatment breaks. The planned CTX and PC cycles were completed in 70% (91% with at least seven of planned nine cycles) and 56% (93% with at least seven of planned eight cycles) of patients, respectively. Toxicity included Grade 3 mucositis (79%), rash (9%), leucopenia (19%), neutropenia (19%), and RT dermatitis (16%). The complete response (CR) rate at the completion of therapy was 84%. The estimated 3-year local regional control rate was 72%. Six patients with an initial CR subsequently experienced a local recurrence, 10 patients experienced distant progression. The median overall survival and disease-free survivals have not been reached. The 3-year actuarial overall survival and disease-free survival were 59% and 58%, respectively. Conclusions: The addition of CTX to weekly PC and daily RT was well tolerated and resulted in encouraging local control and survival rates.

  16. Neuroprotective effect of shenfu injection after intra-arterial thrombolysis

    Institute of Scientific and Technical Information of China (English)

    Huaijun Liu; Xiuchuan Jia; Jiping Yang; Zengpin Liu; Guoshi Wang; Linfang Li

    2006-01-01

    BACKGROUND: Within 3 hours after ischemic stroke, thrombolysis can improve prognosis of patients; however, cerebral edema and cerebral hemorrhage induced by vascular recanalization at an early phase can influence on therapeutic effect of thrombolysis; therefore, thrombolysis is combined with neuroprotective agent for recently clinical treatment.OBJECTIVE: To evaluate the neuroprotective effect of shenfu injection on patients with ischemic stroke after arterial thrombolysis and compare with the controls. DESIGN: Case-controlled study. SETTING : Department of Medical Image, Second Hospital of Hebei Medical University. PARIICIPANTS: A total of 45 patients with acute stroke were selected from Emergency Department or Neurological Department of the Second Hospital of Hebei Medical University from August 2005 to May 2006. All patients were met the diagnosis criteria published by the Fourth National Stroke Conference and had middle cerebral arterial embolism with angiography. Attacked course was less than 6 hours. Patients did not have a history of stroke. Scores of the National Institutes of Health Stroke Scale (NIHSS) were not less than 4 points and patients were aged from 18 to 80 years. All subjects consented of the whole therapeutic process. METHODS: ① Intermittent perfusion was used to treat intra-arterial thrombolysis. Thirty patients with vascular recanalization or partially vascular recanalization (18 males and 12 females) were randomly divided into treatment group and control group with 15 in each group. There was no significant difference of baseline data between the two groups. After recanalization, patients in treatment group were given 20 mL shenfu injection, which consisted of ginseng saponin and aconitine (Ya'an Sanjiu Pharmaceutical Company, batch number: 041013, 10 mL/ampoule) and slowly injected into vein for longer than 5 minutes. And then, patients were intravenously dripped with 50 mL shenfu injection and 50 g/L 250 mL glucose solution once a day

  17. Intra-arterial adenoviral mediated tumor transfection in a novel model of cancer gene therapy

    Directory of Open Access Journals (Sweden)

    Siemionow Maria

    2006-08-01

    Full Text Available Abstract Background The aim of the present study was to develop and characterize a novel in vivo cancer gene therapy model in which intra-arterial adenoviral gene delivery can be characterized. In this model, the rat cremaster muscle serves as the site for tumor growth and provides convenient and isolated access to the tumor parenchyma with discrete control of arterial and venous access for delivery of agents. Results Utilizing adenovirus encoding the green fluorescent protein we demonstrated broad tumor transfection. We also observed a dose dependant increment in luciferase activity at the tumor site using an adenovirus encoding the luciferase reporter gene. Finally, we tested the intra-arterial adenovirus dwelling time required to achieve optimal tumor transfection and observed a minimum time of 30 minutes. Conclusion We conclude that adenovirus mediated tumor transfection grown in the cremaster muscle of athymic nude rats via an intra-arterial route could be achieved. This model allows definition of the variables that affect intra-arterial tumor transfection. This particular study suggests that allowing a defined intra-tumor dwelling time by controlling the blood flow of the affected organ during vector infusion can optimize intra-arterial adenoviral delivery.

  18. Concurrent radiotherapy and chemotherapy with carboplatin in patients with unresectable advanced head and neck tumors stages III and IV; Simultane Radiochemotherapie mit Carboplatin bei Patienten mit inoperablen fortgeschrittenen Kopf-Hals-Tumoren der Stadien UICC III und IV

    Energy Technology Data Exchange (ETDEWEB)

    Muecke, R.; Ziegler, P.G.; Libera, T.; Fietkau, R. [Rostock Univ. (Germany). Klinik und Poliklinik fuer Strahlentherapie; Blynow, M.; Dommerich, S.; Kramp, B. [Rostock Univ. (Germany). HNO-Klinik und Poliklinik; Kundt, G. [Rostock Univ. (Germany). Inst. fuer Medizinische Informatik und Biometrie

    1999-05-01

    Background: The results of treating advanced tumors in the head and neck region with radiotherapy alone are disappointing. Concurrent radiotherapy and chemotherapy may improve this situation. The treatment results of concurrent radiochemotherapy at the University of Rostock were analyzed retrospectively. Results: Six weeks after radiochemotherapy 56.5% of patients had a complete remission, 36% a partial remission and 7.5% `no change`. With a median follow-up of 42 months (6 to 74 months) overall survival, disease-free survival and local control were 24.3%, 28.9%, 18.0% 5 years after treatment. All these criteria were significantly better in patients with palliative tumor resection compared to no surgical treatment (uni- and multivariate) and in patients with Stage III than in patients with Stage IV carcinomas (univariate), overall survival was significantly better in patients with Stage III (multivariate). A pretherapeutic Hb level below 7.0 mmol/l (11.27 g/dl) reduced the local control significantly (uni- and multivariate). Grade III and IV mucositis was detected in 10%, Grade III leucopenia in 12% of treated patients. Grade IV leucopenia and Grade III thrombopenia were observed in 1 patient each. Conclusion: The toxicity of this treatment is tolerable. However, additional trials must be conducted before considering the palliative tumor resection as standard therapy. (orig./AJ) [Deutsch] Hintergrund: Die Therapieergebnisse der Behandlung fortgeschrittener Tumoren der Kopf-Hals-Region mit alleiniger Bestrahlung sind unbefriedigend. Eine simultane Radiochemotherapie verbessert diese Resultate vermutlich. In einer retrospektiven Analyse wurden Ergebnisse nach simultaner Radiochemotherapie an der Universitaet Rostock ausgewertet. Ergebnisse: Sechs Wochen nach Radiochemotherapie erreichten 56,5% der Patienten eine komplette und 36% der Patienten eine partielle Remission, ein `no change` war bei 7,5% der Patienten festzustellen. Bei einer medianen Beobachtungszeit von

  19. Is it relevant that intra-arterial chemotherapy may be effective for advanced pancreatic cancer?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic.Gemcitabine is a promising new agent that has been studied recently for palliation of advanced pancreatic cancer. However, the response rates have been highly variable, and are often irreproducible. To improve this low response rate, various treatments are needed because no standard treatment exists. Intra-arterial chemotherapy is considered to take advantage of the first pass effect of the drug, generating higher local drug concentrations in tumor cells with lower toxicity.Regional intra-arterial chemotherapy may provide high levels of cytostatic concentrations within the tumor and, simultaneously, a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. Intra-arterial chemotherapy has been introduced as an alternative treatment for advanced pancreatic cancer. Further clinical trials of this method should be subjected to a prospective randomized controlled study for advanced pancreatic cancer.

  20. Combination of retrograde superselective intra-arterial chemotherapy and Seldinger method in locally advanced oral cancer

    Directory of Open Access Journals (Sweden)

    Masataka Uehara

    2015-01-01

    Full Text Available The nonsurgical strategies for locally advanced oral cancer are desirable. Superselective intra-arterial infusion with radiotherapy was utilized for this purpose, and there are two types of superselective intra-arterial infusion methods: The Seldinger method and the retrograde superselective intra-arterial chemotherapy (HFT method. In one case, the HFT method was applied to locally advanced tongue cancer, and the Seldinger method was used for additional administration of cisplatin (CDDP to compensate for a lack of drug flow in the HFT method. In another case, the HFT method was applied to locally advanced lower gingival cancer. The Seldinger method was applied to metastatic lymph nodes. In both cases, additional administration of CDDP using the Seldinger method resulted in a complete response. The combination of the HFT and Seldinger methods was useful to eradicate locally advanced oral cancer because each method compensated for the defects of the other.

  1. Combination of retrograde superselective intra-arterial chemotherapy and Seldinger method in locally advanced oral cancer.

    Science.gov (United States)

    Uehara, Masataka; Ohya, Ryouichi; Kodama, Masaaki; Shiraishi, Takeshi; Asahina, Izumi; Tominaga, Kazuhiro

    2015-01-01

    The nonsurgical strategies for locally advanced oral cancer are desirable. Superselective intra-arterial infusion with radiotherapy was utilized for this purpose, and there are two types of superselective intra-arterial infusion methods: The Seldinger method and the retrograde superselective intra-arterial chemotherapy (HFT method). In one case, the HFT method was applied to locally advanced tongue cancer, and the Seldinger method was used for additional administration of cisplatin (CDDP) to compensate for a lack of drug flow in the HFT method. In another case, the HFT method was applied to locally advanced lower gingival cancer. The Seldinger method was applied to metastatic lymph nodes. In both cases, additional administration of CDDP using the Seldinger method resulted in a complete response. The combination of the HFT and Seldinger methods was useful to eradicate locally advanced oral cancer because each method compensated for the defects of the other.

  2. Complete recovery following intra-arterial tenecteplase administration in a woman with acute ischemic stroke.

    Science.gov (United States)

    Meenakshi-Sundaram, S; Periakaruppan, A; Karuppiah, S N K P; Karthik, S N; Roopakumar, L; Thembavani, I

    2013-12-01

    A 23-year-old woman, who underwent a percutaneous transluminal mitral commissurotomy for a tight mitral stenosis, developed an acute ischemic stroke involving the proximal right middle cerebral artery territory. She had a dense left hemiplegia with a National Institutes of Health Stroke Scale score of 12. She was emergently treated within 1 hour with intra-arterial tenecteplase and made a dramatic recovery. Intra-arterial tenecteplase is an attractive option for treating acute ischemic stroke with proximal or major vessel occlusion.

  3. Clinical significance of preoperative regional intra-arterial infusion chemotherapy for advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Cheng-Wu Zhang; Shou-Chun Zou; Dun Shi; Da-Jian Zhao

    2004-01-01

    AIM: Preoperative intra-arterial infusion chemotherapy could increase the radical resection rate of advanced gastric cancer, but its effect on the long-term survival has not been assessed. This study was designed to evaluate the clinical significance of preoperative intra-arterial infusion chemotherapy for advanced gastric cancer.METHODS: Clinicopathological data of 91 patients who underwent curative resection for advanced gastric cancer were collected. Among them, 37 patients undertaken preoperative intra-arterial infusion chemotherapy were used as the interventional chemotherapy group, and the remaining 54 patients as the control group. Eleven factors including clinicopathological variables, treatment procedures and molecular biological makers that might contribute to the long-term survival rate were analyzed using Cox multivariate regression analysis.RESULTS: The 5-year survival rate was 52.5% and 39.8%,respectively, for the interventional group and the control group (P<0.05). Cox multivariate regression analysis revealed that the TNM stage (P<0.001), preoperative intraarterial infusion chemotherapy (P = 0.029) and growth pattern (P = 0.042) were the independent factors for the long-term survival of patients with advanced gastric cancer.CONCLUSION: Preoperative intra-arterial infusion chemotherapy plays an important role in improving the prognosis of advanced gastric cancer.

  4. Globe Salvage With Intra-Arterial Topotecan-Melphalan Chemotherapy in Children With a Single Eye.

    Science.gov (United States)

    Leal-Leal, Carlos A; Asencio-López, Laura; Higuera-Calleja, Jesús; Bernal-Moreno, Max; Bosch-Canto, Vanessa; Chávez-Pacheco, Juan; Isaac-Otero, Gabriela; Beck-Popovic, Maja

    2016-01-01

    Intra-arterial chemotherapy is a novel therapeutic modality for retinoblastoma patients. Intra-arterial chemotherapy involves the administration of a super-selective drug through the ophthalmic artery, resulting in better ocular penetration and low systemic toxicity. The aim of this report was to evaluate the feasibility of intra-arterial chemotherapy in a large referral center in Mexico City. We included patients with bilateral retinoblastoma, one enucleation, and active disease in the other eye after at least two courses of systemic chemotherapy combined with topical treatments. All patients were treated with three courses of a combination of melphalan 4 mg and topotecan 1 mg. Patients were examined under general anesthesia three weeks after each chemotherapy cycle. From 14 eligible patients, three could not be treated due to inaccessibility of the ophthalmic artery. A complete response was observed in 5/11 patients, three in Stage C according to the International Classification for Intraocular Retinoblastoma, one in Stage D, and one in Stage B. The eyes of three patients were enucleated as a result of active/progressive disease, one in Stage B and two in Stage D. Eye preservation was 55% after a mean follow-up of 171 days (range 21-336). Super-selective intra-arterial chemotherapy is safe and effective for preventing the enucleation of 55% of affected eyes in this group of patients.

  5. Local intra-arterial thrombolysis in a 4-year-old male with vertebrobasilar artery thrombosis

    NARCIS (Netherlands)

    Janmaat, Mirjam; Gravendeel, Joost P; Uyttenboogaart, Maarten; Vroomen, Patrick C; Brouwer, Oebele F; Luijckx, Gert-Jan

    2009-01-01

    We report the case of a 4-year-old male with vertebrobasilar artery thrombosis for which he was treated with local intra-arterial urokinase 60 hours after onset of symptoms. Initially the patient had dysarthria and dysphagia. Brain magnetic resonance imaging (MRI) in a community hospital showed abno

  6. In vitro evaluation of the PUCA II intra-arterial LVAD

    NARCIS (Netherlands)

    Vandenberghe, S; Van Loon, JP; Segers, P; Rakhorst, G; Verdonck, P

    2003-01-01

    The "pulsatile catheter" (PUCA) pump is a minimally invasive intra-arterial left ventricular assist device intended for acute support of critically ill heart failure patients. To assess the hydrodynamic performance of the PUCA II, driven by an Arrow AutoCat IABP driver, we used a (static) mock circu

  7. Intra-arterial nimodipine for the treatment of vasospasm due to aneurysmal subarachnoid hemorrhage

    OpenAIRE

    Chiriac A.; Ion Georgiana; Dobrin N.; Faiyad Z.; Poeată I.

    2016-01-01

    The cerebral vasospasm is still considered the most devastating complication for the patients with aneurysmal subarachnoid haemorrhage. The aim of this study was to evaluate the efficiency of intra-arterial nimodipine administration in cerebral vasospasm diminutions and outcome of the patients.

  8. Experimental intra-arterial administration of SR-2508 in the rabbit V2 carcinoma model

    Energy Technology Data Exchange (ETDEWEB)

    Coldwell, D.M.; Huff, J.; Marcellus, H.; Coldwell, S.G.

    1989-03-01

    The use of the nitroimidazole radiation sensitizers, misonidazole and SR-2508, has been limited by a variety of side-effects, principally peripheral neuropathies. To increase the effectiveness of radiosensitization and reduce the administered dose of the sensitizers, intra-arterial delivery of SR-2508 was performed and followed with 10Gy of 4 MeV photon beam radiotherapy in the rabbit V2 carcinoma tumour model. Comparison was made with rabbits treated with an identical dose of SR-2508 given intravenously prior to photon beam radiotherapy. Control animals were treated with radiation therapy only, intra-arterial SR-2508 only, or had no treatment. Neither radiation therapy alone nor SR-2508 alone had any effect on tumour growth. In the intra-arterial group, tumour growth was slower and size was significantly smaller than all other groups. Results suggest that the intra-arterial infusion of radiation sensitizer produces greater tumour response than intravenous infusion when each is combined with radiation therapy.

  9. Repeated Intra-Arterial Thrombectomy within 72 Hours in a Patient with a Clear Contraindication for Intravenous Thrombolysis

    Directory of Open Access Journals (Sweden)

    Mona Laible

    2015-01-01

    Full Text Available Introduction. Treating patients with acute ischemic stroke, proximal arterial vessel occlusion, and absolute contraindication for administering intravenous recombinant tissue plasminogen activator (rtPA poses a therapeutic challenge. Intra-arterial thrombectomy constitutes an alternative treatment option. Materials and Methods. We report a case of a 57-year-old patient with concomitant gastric adenocarcinoma, who received three intra-arterial thrombectomies in 72 hours due to repeated occlusion of the left medial cerebral artery (MCA. Findings. Intra-arterial recanalization of the left medial cerebral artery was performed three times with initially good success. However, two days later, the right medial cerebral artery became occluded. Owing to the overall poor prognosis at that time and knowing the wishes of the patient, we decided not to perform another intra-arterial recanalization procedure. Conclusion. To our knowledge, this is the first case illustrating the use of repeated intra-arterial recanalization in early reocclusion of intracranial vessels.

  10. NRG Oncology/RTOG 0921: A phase 2 study of postoperative intensity-modulated radiotherapy with concurrent cisplatin and bevacizumab followed by carboplatin and paclitaxel for patients with endometrial cancer.

    Science.gov (United States)

    Viswanathan, Akila N; Moughan, Jennifer; Miller, Brigitte E; Xiao, Ying; Jhingran, Anuja; Portelance, Lorraine; Bosch, Walter R; Matulonis, Ursula A; Horowitz, Neil S; Mannel, Robert S; Souhami, Luis; Erickson, Beth A; Winter, Kathryn A; Small, William; Gaffney, David K

    2015-07-01

    The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer. Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months. Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma. © 2015 American Cancer Society.

  11. Thermochemoradiation Therapy Using Superselective Intra-arterial Infusion via Superficial Temporal and Occipital Arteries for Oral Cancer With N3 Cervical Lymph Node Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Mitsudo, Kenji, E-mail: mitsudo@yokohama-cu.ac.jp [Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Koizumi, Toshiyuki; Iida, Masaki; Iwai, Toshinori; Oguri, Senri [Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Yamamoto, Noriyuki [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya (Japan); Itoh, Yoshiyuki [Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Kioi, Mitomu; Hirota, Makoto; Tohnai, Iwai [Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-08-01

    Purpose: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer. Methods and Materials: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m{sup 2}; CDDP, total 100-150 mg/m{sup 2}) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks. Results: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971;1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively. Conclusions: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3

  12. Lymphoscintigraphic evaluation of intra-arterial lymphocyte injection in patients with leg lymphedema

    Energy Technology Data Exchange (ETDEWEB)

    Suga, Kazuyoshi; Uchisako, Hiroji; Yoneshiro, Shu; Fujita, Takefumi; Nakanishi, Takashi; Wakamatsu, Takafumi; Esato, Kensuke (Yamaguchi Univ., Ube (Japan). School of Medicine)

    1992-05-01

    Three patients with chronic leg lymphedema were treated by intra-arterial lymphocyte injection and the effect was evaluated by lymphoscintigraphy using intradermal injection of {sup 99m}Tc-HSA. In all of the patients, the followed-up lymphoscintigraphy showed disappearance of the abnormalities of dermal back flow and/or collateral pathways observed before treatment and these findings were thought to indicate reduced load of dermal lymphatics induced by the treatment. These results indicated the usefulness of imaging with intradermal injection of {sup 99m}Tc-HSA for assessing the effect of treatment with intra-arterial lymphocyte injection. In addition, in two patients of them, analysis of lymph flow after treatment was underwent by time-activity curves obtained by lymphoscintigraphy using a load produced by standing. We also described the significance of the load test with standing. (author).

  13. Efficacy of intra-arterial nimodipine in the treatment of cerebral vasospasm complicating subarachnoid haemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Hui, C. [Department of Diagnostic Imaging, Monash Medical Centre, Clayton, Vic. (Australia)]. E-mail: cathryn.hui@southernhealth.org.au; Lau, K.P. [Department of Diagnostic Imaging, Monash Medical Centre, Clayton, Vic. (Australia)

    2005-09-01

    AIM: To examine the efficacy and safety of nimodipine as an alternative to papaverine for the treatment of cerebral vasospasm following subarachnoid haemorrhage. METHODS: We retrospectively reviewed the procedure reports, anaesthetic records, clinical charts and CT and angiographic images of 9 patients who had received intra-arterial nimodipine; 1 of these patients received both nimodipine and papaverine. The difference in arterial luminal diameter before and after treatment was calculated as a percentage change. RESULTS: The average dose of nimodipine administered per vessel was 3.3 mg. The mean increase in arterial diameter was 66.6% in the vasospastic segment. There was no significant change in blood pressure of any of the subjects during endovascular treatment of vasospasm. CONCLUSION: Intra-arterial nimodipine is effective in improving angiographic vasospasm complicating subarachnoid haemorrhage. Further studies aimed at examining the clinical benefits of nimodipine are warranted, particularly in view of the low risk of adverse side effects of nimopidine when compared with papaverine.

  14. Intra-arterial intervention chemotherapy for sarcoma and cancerous ulcer via an implanted pump.

    Science.gov (United States)

    Liu, Cheng; Cui, Qiu; Guo, Jun; Li, Dingfeng; Zeng, Yanjun

    2014-04-01

    To observe the efficacy of intra-arterial chemotherapy with subcutaneously implanted pump for soft tissue sarcoma in extremities and cancerous ulcer. 31 patients with ulcerative skin squamous cell carcinoma or sarcoma in extremities who received treatment during the period from July 2003 to November 2011 at our hospital were recruited, including 15 male and 16 female patients, aging between 14 and 83 with average age of 49 years old. 10 patients had tumor in upper extremities and 21 patients in lower extremities. The pathological types of studied cases include 9 cases with skin squamous cell carcinoma, 6 cases with synovial sarcoma, 5 cases with malignant fibrous histiocytoma, 3 cases with liposarcoma, 3 cases with osteosarcoma, 2 cases with malignant melanoma, 2 cases with epidermoid sarcoma, and 1 case with protuberans. The main symptoms of cancerous ulcer were pain, infection and hemorrhage; All the studied patients were administrated with cisplatin and doxorubicin by intra-arterial chemotherapy pump, and the patients with squamous cell carcinoma were additionally applied with bleomycin and patients with malignant melanoma were additionally applied with dacarbazine. The chemotherapy efficiency was observed after at 3 cycles of intra-arterial chemotherapy. The total remission rate of pain (RR) was 87 %, and total remission rate of ulcer cicatrization (RR) was 71 %, with ulcer cicatrizing spontaneously in 9 cases and obvious homeostasis in 5 cases with bleeding ulcers. 19 patients underwent surgery after chemotherapy, in which 16 cases had limb-salvage surgery and 3 cases underwent lower leg amputation after chemotherapy, and 3 patients out of 16 cases had local recurrence (19 %). The subcutaneous intra-arterial targeting chemotherapy could be applied to treat refractory sarcoma and cancerous ulcer in extremities to significantly increase the chemotherapeutic concentration at tumor area so as to effectively constrain the tumor rupture induced main symptoms

  15. Persistent renal enhancement after intra-arterial versus intravenous iodixanol administration

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Shinn-Huey; Wang, Zhen J.; Kuo, Jonathan; Cabarrus, Miguel; Fu Yanjun; Aslam, Rizwan; Yee, Judy; Zimmet, Jeffrey M.; Shunk, Kendrick; Elicker, Brett [Department of Radiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0628 (United States); Yeh, Benjamin M., E-mail: Benjamin.Yeh@ucsf.edu [Department of Radiology, University of California San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0628 (United States)

    2011-11-15

    Purpose: To examine the clinical significance of persistent renal enhancement after iodixanol administration. Methods: We retrospectively studied 166 consecutive patients who underwent non-enhanced abdominopelvic CT within 7 days after receiving intra-arterial (n = 99) or intravenous (n = 67) iodixanol. Renal attenuation was measured for each non-enhanced CT scan. Persistent renal enhancement was defined as CT attenuation >55 Hounsfield units (HU). Contrast-induced nephropathy (CIN) was defined as a rise in serum creatinine >0.5 mg/dL within 5 days after contrast administration. Results: While the intensity and frequency of persistent renal enhancement was higher after intra-arterial (mean CT attenuation of 73.7 HU, seen in 54 of 99 patients, or 55%) than intravenous contrast material administration (51.8 HU, seen in 21 of 67, or 31%, p < 0.005), a multivariate regression model showed that the independent predictors of persistent renal enhancement were a shorter time interval until the subsequent non-enhanced CT (p < 0.001); higher contrast dose (p < 0.001); higher baseline serum creatinine (p < 0.01); and older age (p < 0.05). The route of contrast administration was not a predictor of persistent renal enhancement in this model. Contrast-induced nephropathy was noted in 9 patients who received intra-arterial (9%) versus 3 who received intravenous iodixanol (4%), and was more common in patients with persistent renal enhancement (p < 0.01). Conclusion: Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients.

  16. Real-Time, In Vivo Monitoring, and Quantitative Assessment of Intra-Arterial Vasospasm Therapy.

    Science.gov (United States)

    Gölitz, Philipp; Kaschka, Iris; Lang, Stefan; Roessler, Karl; Knossalla, Frauke; Doerfler, Arnd

    2016-08-01

    Our study aimed to evaluate whether the effect of an intra-arterial vasospasm therapy can be assessed quantitatively by in vivo blood flow analysis using the postprocessing algorithm parametric color coding (PCC). We evaluated 17 patients presenting with acute clinical deterioration due to vasospasm following subarachnoidal hemorrhage treated with intra-arterial nimodipine application. Pre- and post-interventional DSA series were post-processed by PCC. The relative time to maximum opacification (rTmax) was calculated in 14 arterially and venously located points of interest. From that data, the pre- and post-interventional cerebral circulation time (CirT) was calculated. Additionally, the arterial vessel diameters were measured. Pre- and post-interventional values were compared and tested for significance, respectively. Flow analysis revealed in all arterial vessel segments a non-statistically significant prolongation of rTmax after treatment. The mean CirT was 5.62 s (±1.19 s) pre-interventionally and 5.16 s (±0.81 s) post-interventionally, and the difference turned out as statistically significant (p = 0.039). A significantly increased diameter was measurable in all arterial segments post-interventionally. PCC is a fast applicable imaging technique that allows via real-time and in vivo blood flow analysis a quantitative assessment of the effect of intra-arterial vasospasm therapy. Our results seem to validate in vivo that an intra-arterial nimodipine application induces not only vasodilatation of the larger vessels, but also improves the microcirculatory flow, leading to a shortened cerebral CirT that reaches normal range post-interventionally. Procedural monitoring via PCC offers the option to compare quantitatively different therapy regimes, which allows optimization of existing approaches and implementation of individualized treatment strategies.

  17. Admission Glucose and Effect of Intra-Arterial Treatment in Patients With Acute Ischemic Stroke.

    Science.gov (United States)

    Osei, Elizabeth; den Hertog, Heleen M; Berkhemer, Olvert A; Fransen, Puck S S; Roos, Yvo B W E M; Beumer, Debbie; van Oostenbrugge, Robert J; Schonewille, Wouter J; Boiten, Jelis; Zandbergen, Adrienne A M; Koudstaal, Peter J; Dippel, Diederik W J

    2017-05-01

    Hyperglycemia on admission is common after ischemic stroke. It is associated with unfavorable outcome after treatment with intravenous thrombolysis and after intra-arterial treatment. Whether hyperglycemia influences the effect of reperfusion treatment is unknown. We assessed whether increased admission serum glucose modifies the effect of intra-arterial treatment in patients with acute ischemic stroke. We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose >7.8 mmol/L. The primary outcome measure was the adjusted common odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale at 90 days, estimated with ordinal logistic regression. Secondary outcome variable was symptomatic intracranial hemorrhage. We assessed treatment effect modification of hyperglycemia and admission serum glucose levels with multiplicative interaction factors and adjusted for prognostic variables. Four hundred eighty-seven patients were included. Mean admission serum glucose was 7.2 mmol/L (SD, 2.2). Fifty-seven of 226 patients (25%) randomized to intra-arterial treatment were hyperglycemic compared with 61 of 261 patients (23%) in the control group. The interaction of either hyperglycemia or admission serum glucose levels and treatment effect on modified Rankin Scale scores was not significant (P=0.67 and P=0.87, respectively). The same applied for occurrence of symptomatic hemorrhage (P=0.39 for hyperglycemia, P=0.39 for admission serum glucose). We found no evidence for effect modification of intra-arterial treatment by admission serum glucose in patients with acute ischemic stroke. URL: www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

  18. Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study.

    Science.gov (United States)

    Hancı, Volkan; Özbilgin, Şule; Özbal, Seda; Kamacı, Gonca; Ateş, Hasan; Boztaş, Nilay; Ergür, Bekir Uğur; Arıkanoğlu, Ahmet; Yılmaz, Osman; Yurtlu, Bülent Serhan

    2016-01-01

    Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1μg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated. There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (psugammadex groups in histological scores. Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  19. [Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study].

    Science.gov (United States)

    Hancı, Volkan; Özbilgin, Şule; Özbal, Seda; Kamacı, Gonca; Ateş, Hasan; Boztaş, Nilay; Ergür, Bekir Uğur; Arıkanoğlu, Ahmet; Yılmaz, Osman; Yurtlu, Bülent Serhan

    2016-01-01

    Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1μg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated. There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (psugammadex groups in histological scores. Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  20. Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study

    Directory of Open Access Journals (Sweden)

    Volkan Hancı

    Full Text Available Abstract Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Methods: Rabbits were randomly divided into 4 groups. Group Control (n = 7; no intervention performed. Group Catheter (n = 7; a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n = 7; rabbits were given 4 mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n = 7; rabbits were given 1 µg/kg dexmedetomidine into the central artery of the ear. After 72 h, the ears were amputated and histologically investigated. Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p < 0.05. There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

  1. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Madaric, Juraj, E-mail: jurmad@hotmail.com [National Institute of Cardiovascular Diseases (NUSCH) and Slovak Medical University, Department of Cardiology and Angiology (Slovakia); Klepanec, Andrej [National Institute of Cardiovascular Diseases, Department of Diagnostic and Interventional Radiology (Slovakia); Mistrik, Martin [Clinic of Hematology and Transfusiology, Faculty Hospital (Slovakia); Altaner, Cestmir [Slovak Academy of Science, Institute of Experimental Oncology (Slovakia); Vulev, Ivan [National Institute of Cardiovascular Diseases, Department of Diagnostic and Interventional Radiology (Slovakia)

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  2. Intra-arterial pulmonary thrombolysis at the postoperative period of brain aneurysm clamping: case report.

    Science.gov (United States)

    Rojas, Salomón Soriano Ordinola; Veiga, Viviane Cordeiro; Carvalho, Júlio César de; Campodônico, Luis Enrique Amaya; Assis, Fabrizio Rodrigues; Shimizu, Sandra Patrícia; Morais, Elaine Aparecida; Buesio, Roberto; Marchesini, Andréia Maria; Junqueira, Ligia Maria Coscrato; Holanda, Carlos Vanderlei

    2008-09-01

    Pulmonary thromboembolism is a major cause of morbidity and mortality of patients undergoing neurosurgical procedures. The purpose of this study was to present a case of intra-arterial pulmonary thrombolysis in recent neurosurgery postoperative period. Male patient, undergoing neurosurgery, presented as a complication on the seventh day of postoperative massive pulmonary embolism with hemodynamic instability and intraarterial pulmonary thrombolysis with alteplase was indicated. Evolution was satisfactory without bleeding complications and patient was discharged. Pulmonary thromboembolism is a high morbidity and mortality condition at neurosurgical postoperative period and thrombolysis should be an alternative therapy in cases refractory to clinical treatment.

  3. CT findings in ischaemic hepatic failure due to intra-arterial embolisation: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Catalano, O. [Dept. of Radiological Sciences, Univ. `Federico II`, Naples (Italy)

    1997-01-01

    Liver infarction is relatively uncommon. It may be secondary to several conditions such as sepsis, shock, sickle-cell anaemia, eclampsia, vasculitis, metastatic disease, bacterial endocarditis, rheumatic heart disease, trauma, portal venous occlusion or compression, oral contraception, anaesthesia, hepatic artery thrombosis, therapeutical or inadvertent hepatic artery ligation, intra-arterial chemotherapy or embolisation. A case of hepatic infraction, unusual for iatrogenic pathogenesis, submassive extension with acute hepatic failure, and CT findings of an internally branching pattern due to intravascular gas was observed. (orig./AJ)

  4. Supraselective intra-arterial chemotherapy: evaluation of treatment-related complications in advanced retinoblastoma

    Directory of Open Access Journals (Sweden)

    Lejla Mutapcic Vajzovic

    2011-02-01

    Full Text Available Lejla Mutapcic Vajzovic1, Timothy G Murray1, Mohammad A Aziz-Sultan2, Amy C Schefler1, Stacey Quintero Wolfe2, Ditte Hess1, Cristina E Fernandes3, Sander R Dubovy1,41Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Neurological Surgery, University of Miami/Jackson Memorial Hospital, Miami, FL, USA; 3Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA; 4Florida Lions Oculopathology Laboratory, Miami, FL, USA Purpose: The purpose of this study is to report the complication profile and safety evaluation of supraselective intra-arterial melphalan chemotherapy in children undergoing treatment with advanced retinoblastoma.Methods: Twelve eyes of 10 children with advanced retinoblastoma (Reese-Ellsworth Group Vb or International Classification Group D were treated with supraselective intra-ophthalmic artery infusion of melphalan. Eleven eyes of nine children had previously failed traditional management with systemic chemotherapy and laser ablation and underwent intra-ophthalmic artery infusion of melphalan as an alternative to enucleation. Serial ophthalmic examinations, retinal photography, and ultrasonographic imaging were used to evaluate treatment regime.Results: Ophthalmic artery cannulation was successfully performed in 12 eyes of 10 patients (total 16 times. Striking regression of tumor, subretinal and vitreous seeds were seen early in each case. No severe systemic side effects occurred. Grade III neutropenia was seen in one patient. No transfusions were required. Three patients developed a vitreous hemorrhage obscuring tumor visualization. One patient developed periocular edema associated with inferior rectus muscle inflammation per orbital MRI. This same patient had scattered intraretinal hemorrhages and peripapillary cotton wool spots consistent with a Purtscher’s-like retinopathy that resolved spontaneously. At the 6-month follow-up examination

  5. Transplantation of hematopoietic stem cells: intra-arterial versus intravenous administration impacts stroke outcomes in a murine model.

    Science.gov (United States)

    Kasahara, Yukiko; Yamahara, Kenichi; Soma, Toshihiro; Stern, David M; Nakagomi, Takayuki; Matsuyama, Tomohiro; Taguchi, Akihiko

    2016-10-01

    Based on results of hematopoietic stem cell transplantation in animal models of stroke, clinical trials with hematopoietic stem cells administered intra-arterially or intravenously have been initiated in patients. Although intra-arterial injection is expected to deliver transplanted cells more directly to the ischemic tissue, the optimal route for enhancing clinical outcomes has not been identified in the setting of stroke. In this study, we compared the therapeutic potential of intra-arterial versus intravenous injection of bone marrow derived-mononuclear cells (BM-MNCs) and CD133-positive (CD133(+)) cells in a murine stroke model. We have found that intra-arterial injection of BM-MNCs exaggerates inflammation with accompanying loss of microvascular structures in poststroke brain and no improvement in cortical function. In contrast, intravenous injection of BM-MNCs did not similarly enhance inflammation and improved cortical function. Our results indicate that the optimal route of cell transplantation can vary with different cell populations and highlight possible issues that might arise with intra-arterial cell administration for acute ischemic cerebrovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. MRI evaluation of frequent complications after intra-arterial transplantation of mesenchymal stem cells in rats

    Science.gov (United States)

    Namestnikova, D.; Gubskiy, I.; Gabashvili, A.; Sukhinich, K.; Melnikov, P.; Vishnevskiy, D.; Soloveva, A.; Vitushev, E.; Chekhonin, V.; Gubsky, L.; Yarygin, K.

    2017-08-01

    Intra-arterial transplantation of mesenchymal stem cells (MSCs) is an effective delivery route for treatment of ischemic brain injury. Despite significant therapeutic effects and targeted cells delivery to the brain infraction, serious adverse events such as cerebral embolism have been reported and may restrict potential clinical applications of this method. In current study, we evaluate potential complications of intra-arterial MSCs administration and determine the optimum parameters for cell transplantation. We injected SPIO-labeled human MSCs via internal carotid artery with different infusion parameters and cell dose in intact rats and in rats with the middle cerebral occlusion stroke model. Cerebrovascular complications and labeled cells were visualized in vivo using MRI. We have shown that the incidence of cerebral embolic events depends on such parameters as cell dose, infusion rate and maintenance of blood flow in the internal carotid artery (ICA). Optimal parameters were considered to be 5×105 hMSC in 1 ml of PBS by syringe pump with velocity 100 μ/min and maintenance of blood flow in the ICA. Obtained data should be considered before planning experiments in rats and, potentially, can help in planning clinical trials in stroke patients.

  7. Role of selective intra-arterial embolization in benign liver tumors.

    Science.gov (United States)

    Ferrer Puchol, M D; Parra Casado, C La; Cervera Araez, A; Sala López, R; Esteban Hernández, E; Cremades Mira, A; Ramiro Gandia, R

    To present cases of symptomatic benign liver tumors diagnosed and treated with intra-arterial embolization before surgery. We present the cases of 7 patients diagnosed with symptomatic benign liver tumors that required treatment: 1 focal nodular hyperplasia, 2 giant cavernous hemangiomas, 1 hepatic adenomatosis, and 3 hepatic adenomas. Once the feeding arteries were identified, tumors were embolized with polyvinyl alcohol particles (500μm-700μm) and then the feeding artery was plugged with coils if there was an arterial pedicle to ensure the total vascular exclusion of the tumor. The surgical intervention took place 4 to 7 days after embolization. All 7 patients were women (age range, 23-74 years); presurgical intra-arterial embolization was done in 6. In 1 patient with adenomatosis, embolization was done to control intraparenchymal hepatic hemorrhage. In the 6 patients who underwent surgery, the tumor was completely excised and no intraoperative bleeding events or postoperative complications occurred. Provided there is a consensus among the multidisciplinary team, embolization is a useful option in the perioperative management of giant and/or symptomatic benign liver tumors. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Multimodal Imaging of Nanocomposite Microspheres for Transcatheter Intra-Arterial Drug Delivery to Liver Tumors

    Science.gov (United States)

    Kim, Dong-Hyun; Li, Weiguo; Chen, Jeane; Zhang, Zhuoli; Green, Richard M.; Huang, Sui; Larson, Andrew C.

    2016-01-01

    A modern multi-functional drug carrier is critically needed to improve the efficacy of image-guided catheter-directed approaches for the treatment of hepatic malignancies. For this purpose, a nanocomposite microsphere platform was developed for selective intra-arterial transcatheter drug delivery to liver tumors. In our study, continuous microfluidic methods were used to fabricate drug-loaded multimodal MRI/CT visible microspheres that included both gold nanorods and magnetic clusters. The resulting hydrophilic, deformable, and non-aggregated microspheres were mono-disperse and roughly 25 um in size. Sustained drug release and strong MRI T2 and CT contrast effects were achieved with the embedded magnetic nano-clusters and radiopaque gold nanorods. The microspheres were successfully infused through catheters selectively placed within the hepatic artery in rodent models and subsequent distribution in the targeted liver tissues and hepatic tumors confirmed with MRI and CT imaging. These multimodal nanocomposite drug carriers should be ideal for selective intra-arterial catheter-directed administration to liver tumors while permitting MRI/CT visualization for patient-specific confirmation of tumor-targeted delivery. PMID:27405824

  9. Terapia trombolítica intra-arterial intra-operatória

    Directory of Open Access Journals (Sweden)

    Ana Terezinha Guillaumon

    Full Text Available OBJETIVO: Apresentar um tratamento coadjuvante à desobstrução mecânica, nas oclusões arteriais agudas de membros. MÉTODO: A impossibilidade de desobstrução mecânica cirúrgica completa dos vasos tem levado a altas taxas de amputações. Utilizamos como coadjuvante desta a aplicação de agente trombolítico intra-operatório, intra-arterial regional, seguida da infusão de solução de diálise peritoneal à baixa temperatura. RESULTADO: Neste pequeno grupo de doentes, verificamos que o uso de fibrinolítico seguido da lavagem da árvore arterial com solução preservadora, à baixa temperatura, aumenta a taxa de sucesso cirúrgico com preservação do membro e sua função. CONCLUSÃO: A terapia trombolítica intra-arterial regional, associada ao uso de solução de diálise peritoneal heparinizada, apresentou um percentual de sucesso de 88,88% dos casos tratados com este método.

  10. Rabbit Model of Human Gliomas: Implications for Intra-Arterial Drug Delivery

    Science.gov (United States)

    Qin, Huamin; Janowski, Miroslaw; Pearl, Monica S.; Malysz-Cymborska, Izabela; Li, Shen; Eberhart, Charles G.

    2017-01-01

    The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices. To date, however, no protocols are available that enable human glioma modeling in rabbits. In this article, we report on the xenotransplantation of a human glioblastoma (GBM-1) in adult New Zealand rabbits. We induced multi-drug immunosuppression (Mycophenolate Mofetil, Dexamethasone, Tacrolimus) and stereotactically implanted GBM-1 tumor cells into rabbit brains. The rabbits were followed for 42 days, monitored by MRI and body weight measurements, and underwent postmortem histopathological analysis. On MRI, brain tumors were identified on T2-weighted scans. On histopathology, tumors were detected with hematoxylin/eosin and their human origin was confirmed with immunohistochemistry against human-specific antigens. Our method for human glioma modeling in rabbits provides the foundation to test novel treatment strategies, including intra-arterial therapeutic agent delivery. PMID:28103265

  11. Intentional intra-arterial injection of midazolam in a patient with status epilepticus in the intensive care unit

    Directory of Open Access Journals (Sweden)

    Muhammad Asghar Ali

    2017-01-01

    Full Text Available Fundamental medical care includes intravenous (IV access which provides prompt resuscitation and reliable delivery of analgesics, antibiotics, and vasoactive medication. Difficult access populations, especially in critical area, continue to challenge providers to consider and utilize alternative means to provide IV access. Potential options under such circumstances include intramuscular, intraosseous, and intratracheal drug administration, but in extreme cases where no other options are available, intra-arterial route might be considered. We present a case where midazolam was intentionally injected intra-arterially to abort seizure activity in a patient with status epilepticus in the Intensive Care Unit.

  12. MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors.

    Science.gov (United States)

    Kim, Dong-Hyun; Chen, Jeane; Omary, Reed A; Larson, Andrew C

    2015-01-01

    Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy. These alginate microspheres were synthesized using a highly efficient microfluidic gelation process. The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile. The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro studies. A xenograft rodent model was used to demonstrate the feasibility to deliver these microspheres to liver tumors using hepatic transcatheter intra-arterial infusions and potential to visualize the intra-hepatic delivery of these microspheres to both liver tumor and normal tissues with MRI immediately after infusion. This approach offer the potential for catheter-directed drug delivery to liver tumors for reduced systemic toxicity and superior therapeutic outcomes.

  13. Application of finite element analysis for assessing biocompatibility of intra-arterial catheters and probes.

    Science.gov (United States)

    Bedingham, W; Neavin, T D

    1991-01-01

    A commercial finite element modeling program (FIDAP) was adapted to compute the fluid dynamics of laminar blood flow around an intra-arterial catheter and/or sensor probe. The model provided an accurate transient solution to the Navier-Stokes equations under pulsatile blood flow conditions. To simulate the compliance in the catheter tubing set, a second order convolution integral was incorporated into the boundary conditions. The saline drip rate and catheter compliance could be specified, and the bulk blood flow, blood pressure, and heart rate were varied to simulate specific patient conditions. Analysis of the transient solution was used to assess probable sites for thrombus activation and deposition. The transient velocity and pressure fields identified regions of separated flow and recirculation. The computed shear rates and stresses were used to predict hemolysis, platelet activation, and thrombus formation. Analysis of particle paths provided an estimate of residence times and thrombus deposition sites.

  14. Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke.

    Science.gov (United States)

    Banerjee, Soma; Bentley, Paul; Hamady, Mohammad; Marley, Stephen; Davis, John; Shlebak, Abdul; Nicholls, Joanna; Williamson, Deborah A; Jensen, Steen L; Gordon, Myrtle; Habib, Nagy; Chataway, Jeremy

    2014-11-01

    Treatment with CD34+ hematopoietic stem/progenitor cells has been shown to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. We aimed to determine the safety and feasibility of treatment with CD34+ cells delivered intra-arterially in patients with acute ischemic stroke. This was the first study in human subjects. We performed a prospective, nonrandomized, open-label, phase I study of autologous, immunoselected CD34+ stem/progenitor cell therapy in patients presenting within 7 days of onset with severe anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score≥8). CD34+ cells were collected from the bone marrow of the subjects before being delivered by catheter angiography into the ipsilesional middle cerebral artery. Eighty-two patients with severe anterior circulation ischemic stroke were screened, of whom five proceeded to treatment. The common reasons for exclusion were age>80 years (n=19); medical instability (n=17), and significant carotid stenosis (n=13). The procedure was well tolerated in all patients, and no significant treatment-related adverse effects occurred. All patients showed improvements in clinical functional scores (Modified Rankin Score and NIHSS score) and reductions in lesion volume during a 6-month follow-up period. Autologous CD34+ selected stem/progenitor cell therapy delivered intra-arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials. ©AlphaMed Press.

  15. Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects

    Science.gov (United States)

    Savic, Lynn Jeanette; Chapiro, Julius

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a rare disease and carries a poor prognosis with surgery remaining the only curative treatment option. However, due to the late presentation of symptoms and close proximity of the tumors to central hepatic structures, only about 30% of patients are classified eligible to resection. As for palliative approaches, ICC constitutes a possible indication for loco-regional therapies (LRT). As such, intra-arterial therapies (IAT) are reported to be feasible, safe and effective in inducing tumor response in unresectable ICC. The paradigm of IAT is premised on the selective delivery of embolic, chemotherapeutic agents to the tumor via its feeding arteries, thus allowing dose escalation within the carcinoma and reduction of systemic toxicity. Conventional transcatheter arterial chemoembolization (cTACE) so far remains the most commonly used IAT modality. However, drug-eluting beads (DEB)-TACE was initiated with the idea of more selective targeting of the tumor owing to the combined embolizing as well as drug-eluting properties of the microspheres used in this setting. Moreover, radioembolization is performed by intra-arterial administration of very small spheres containing β-emitting yttrium-90 (Y90-RE) to the site of the tumor. Clinical evidence exists in support of survival benefits for IAT in the palliative treatment of ICC compared to surgery and systemic chemotherapy. As for combination regimens, cTACE, DEB-TACE and Y90-RE are reported to achieve conversion of patients to surgery in a sequential treatment planning and simultaneous IAT combinations may provide a therapeutic option for treatment escalation. Regarding the current status of literature, controlled randomized prospective trials to compare different IAT techniques and combination therapies as well as treatment recommendations for different IAT modalities are needed. PMID:28261591

  16. Blood pressure monitoring during arrhythmia: agreement between automated brachial cuff and intra-arterial measurements.

    Science.gov (United States)

    Lakhal, K; Ehrmann, S; Martin, M; Faiz, S; Réminiac, F; Cinotti, R; Capdevila, X; Asehnoune, K; Blanloeil, Y; Rozec, B; Boulain, T

    2015-10-01

    Since arrhythmia induces irregular pulse waves, it is widely considered to cause flawed oscillometric brachial cuff measurements of blood pressure (BP). However, strong data are lacking. We assessed whether the agreement of oscillometric measurements with intra-arterial measurements is worse during arrhythmia than during regular rhythm. Among patients of three intensive care units (ICUs), a prospective comparison of three pairs of intra-arterial and oscillometric BP readings was performed among patients with arrhythmia and an arterial line already present. After each inclusion in the arrhythmia group, one patient with regular rhythm was included as a control. International Organization for Standardization (ISO) standard validation required a mean bias arterial measurements of systolic, diastolic and mean BP was similar to that observed in 136 patients with regular rhythm: for mean BP, similar mean bias [-0.1 (sd 5.2) and 1.9 (sd 5.9) mm Hg]. In both groups, the ISO standard was satisfied for mean and diastolic BP, but not for systolic BP (sd >10 mm Hg) in our ICU population. The ability of oscillometry to detect hypotension (systolic BP 10% increase in mean BP after cardiovascular intervention) and hypertension (systolic BP >140 mm Hg) was good and similar during arrhythmia and regular rhythm (respective areas under the receiver operating characteristic curves ranging from 0.89 to 0.96, arrhythmia vs regular rhythm between-group comparisons all associated with P>0.3). Contrary to widespread belief, arrhythmia did not cause flawed automated brachial cuff measurements. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Quantitative evaluation of leg lymphedema by MR imaging. Estimation of therapeutic effect by intra-arterial injection of lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Makimoto, Yumi; Harada, Masafumi; Matsuzaki, Kenji; Hayashi, Yoshinori; Nishitani, Hiromu; Yoshizumi, Masanori; Yoshida, Osamu; Katoh, Itsuo [Tokushima Univ. (Japan). School of Medicine

    1994-12-01

    The purpose of this study was to obtain characteristic findings of lymphedema and reactions after intra-arterial lymphocytes injection therapy by MRI and to evaluate quantitatively effect of intra-arterial lymphocytes injection. Five patients were treated by several intra-arterial lymphocytes injections. We measured T{sub 2} value on edematous tissue using triple echo sequence and shot TI IR (STIR) images to assess the extent of lymphedema. MRI was measured before and after each intra-arterial lymphocytes injection. Mean T{sub 2} and standard deviation (SD) of T{sub 2} distribution were obtained from T{sub 2}-calculated images. Characteristic findings of lymphedema were the thickening of subcutaneous, meshed pattern of fluid, thickening of skin, and fluid on the fascia. After therapy, thickness of subcutaneous tissue and meshed pattern were greatly decreased, but thickening of skin and fluid on the fascia still remained. Mean T{sub 2} and SD of T{sub 2} in edematous tissue were much higher than those of normal tissue. Both of them decreased extremely after therapy on improved cases but did not change on less effective cases. STIR could differentiate water from adipose tissue and clearly indicated the distribution of water. Mean T{sub 2} and SD of T{sub 2} distribution were useful to indicate evaluation of lymphedema and assessment of therapy. (author).

  18. Evolution of Intra-arterial Therapy for Acute Ischemic Stroke in the Netherlands : MR CLEAN Pretrial Experience

    NARCIS (Netherlands)

    Rozeman, Anouk D.; Wermer, Marieke J H; Vos, Jan Albert; Nijeholt, Geert J Lycklama À; Beumer, Debbie; Berkhemer, Olvert A.; Dippel, Diederik W J; Algra, Ale; Boiten, Jelis; Schonewille, Wouter J.

    2016-01-01

    Introduction The Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) trial showed efficacy of intra-arterial (IA) treatment in acute ischemic stroke (AIS). We studied the evolution of IA treatment for AIS and its effects on clinical

  19. Facial nerve paralysis after super-selective intra-arterial chemotherapy for oral cancer.

    Science.gov (United States)

    Sugiyama, S; Iwai, T; Oguri, S; Koizumi, T; Mitsudo, K; Tohnai, I

    2017-02-10

    Facial nerve paralysis (FNP) after super-selective intra-arterial chemotherapy (SSIAC) is a relatively rare local side effect of SSIAC to the maxillary artery (MA) or the middle meningeal artery (MMA). The incidence and prognosis of FNP after SSIAC in 381 patients with oral cancer (133 with catheterization of the MA, 248 without) was investigated retrospectively. Only three patients (two male and one female) had FNP, for an incidence of 0.8%. All patients with FNP had undergone catheterization of the MA, and the incidence of FNP in this group was 2.3% (3/133). One of the three patients with FNP had paralysis of the third branch of the trigeminal nerve. FNP occurred a mean of 8.7 days (range 5-11 days) after initial SSIAC, and the mean total dose of cisplatin was 55.8mg (range 42.5-67.2mg) and of docetaxel was 25.4mg (range 17.0-33.6mg). FNP resolved completely a mean of 12.7 months (range 6-19 months) after onset. Because the administration of anticancer agents via the MA or MMA carries a risk of FNP, this information will be useful when obtaining informed consent from patients before treatment.

  20. Dose-rate distribution of {sup 32}P-glass microspheres for intra-arterial brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Guimaraes, Carla C.; Moralles, Mauricio; Sene, Frank F.; Martinelli, Jose R. [Centro de Ciencia e Tecnologia de Materiais, IPEN, Av. Lineu Prestes 2242, Sao Paulo, Sao Paulo 05508-000 (Brazil); Centro do Reator de Pesquisas, Energy and Nuclear Research Institute, IPEN/CNEN, CP 11049, CEP 05422-970, Sao Paulo, Sao Paulo (Brazil); Centro de Ciencia e Tecnologia de Materiais, IPEN, Av. Lineu Prestes 2242, Sao Paulo, Sao Paulo 05508-000 (Brazil)

    2010-02-15

    Purpose: The intra-arterial administration of radioactive glass microspheres is an alternative therapy option for treating primary hepatocellular carcinoma, the main cause of liver cancer death, and metastatic liver cancer, another important kind of cancer induced in the liver. The technique involves the administration of radioactive microspheres in the hepatic artery, which are trapped preferentially in the tumor. Methods: In this work the GEANT4 toolkit was used to calculate the radial dose-rate distributions in water from {sup 32}P-loaded glass microspheres and also from {sup 90}Y-loaded glass microspheres. To validate the toolkit for this application, the authors compared the dose-rate distribution of {sup 32}P and {sup 90}Y point sources in water with data from the International Commission on Radiation Units and Measurements report 72. Results: Tables of radial dose-rate distributions are provided for practical use in brachytherapy planning with these microspheres. Conclusions: The simulations with the microspheres show that the shape of the beta ray energy spectra with respect to the {sup 32}P and {sup 90}Y sources is significantly modified by the glass matrix.

  1. Intra-Arterial Prostaglandin E1 Infusion in Patients with Rest Pain: Short-Term Results

    Directory of Open Access Journals (Sweden)

    A. Chatziioannou

    2012-01-01

    Full Text Available Purpose. To present our results after short-term (1 month intra-arterial infusion therapy of PGE1-alprostadil via a port system implanted in the ipsilateral external iliac artery (EIA in patients with severe rest pain. Methods. Ten patients with severe rest pain were included. All patients showed extensive peripheral vascular disease below the knee. The tip of the catheter was introduced via a retrograde puncture in the ipsilateral external iliac artery (EIA. The patients received intraarterial infusion of PGE1, 20 mgr alprostadil daily, via the port catheter for 1 month. Results. Clinical success was evaluated according to subjective grading of pain (group A significant decrease, group B moderate decrease and group C no response. A significant decrease of rest pain was observed in 8 (group A, 80% patients, a moderate decrease in 2 (Group B, 20%, whereas no patients demonstrated any significant response. Both patients of group B had Buergers' disease and continue to smoke during therapy. No peripheral thrombosis or clinical deterioration was noticed. Conclusion. Intraarterial infusion of PGE1 alprostadil on a daily basis, using a port catheter into the ipsilateral EIA, in selected patients with severe rest pain, seems to be very effective, without any serious complications.

  2. Local intra-arterial thrombolysis in the carotid territory: does recanalization depend on the thromboembolus type?

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H.; Wilhelm, K.; Flacke, S.; Schild, H.H. [Department of Radiology/Neuroradiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany); Hartmann, A.; Pohl, C.; Klockgether, T. [Department of Neurology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany); Omran, H. [Department of Cardiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn (Germany)

    2002-08-01

    Little is known about whether recanalization of carotid territory occlusions by local intra-arterial thrombolysis (LIT) depends on the type of the occluding thromboembolus. We retrospectively analysed the records of 62 patients with thromboembolic occlusions of the intracranial internal carotid artery (ICA) bifurcation or the middle cerebral artery who were undergoing LIT with urokinase within 6 h of symptom onset. We determined the influence of thromboembolus type (according to the TOAST criteria), thromboembolus location, leptomeningeal collaterals, time interval from onset of symptoms to onset of thrombolysis, and patient's age on recanalization. The thromboembolus type was atherosclerotic in six patients, cardioembolic in 29, of other determined etiology in four, and of undetermined etiology in 23 patients. Thirty-three (53%) thromboembolic occlusions were recanalized. The thromboembolus location but not the TOAST stroke type nor other parameters affected recanalization. In the TOAST group of patients with cardioembolic occlusions recanalization occurred significantly less frequently when transoesophageal echocardiography showed cardiac thrombus. The present study underlines the thromboembolus location as being the most important parameter affecting recanalization. The fact that thromboembolic occlusions originating from cardiac thrombi had a lower likelihood of being resolved by thrombolysis indicates the thromboembolus type as another parameter affecting recanalization. (orig.)

  3. Efficacy of intra-arterial treatment for massive gastrointestinal bleeding in hemodialysis patients.

    Science.gov (United States)

    Banshodani, Masataka; Kawanishi, Hideki; Moriishi, Misaki; Shintaku, Sadanori; Sato, Tomoyasu; Tsuchiya, Shinichiro

    2014-02-01

    The incidence of acute nonvariceal massive gastrointestinal bleeding (GIB) is higher in hemodialysis (HD) patients than in healthy individuals, and this is often a life-threatening event. We evaluated the efficacy of intra-arterial treatment for GIB in HD patients. Between January 2006 and June 2012, eight HD patients with GIB were treated with superselective transarterial embolization. Of the eight cases, one was duodenal bleeding, two were jejunal bleeding, one was ileocecum bleeding, two were ascending colonic bleeding, and two were sigmoid colonic bleeding. After examining the site of bleeding by endoscopy or contrast-enhanced computed tomography (CT), embolizations with microcoils, gelatin sponges, or N-butyl cyanoacrylate were performed through interventional radiology (IVR). In all cases, blood transfusions were frequently administered. Six of the eight patients with GIB were successfully salvaged by transarterial embolization. In one case, duodenal bleeding was refractory to endoscopic treatment. Embolization was performed twice in this case; however, the patient died of an aneurysm rupture at the embolization site 24 days after the embolizations. In another case, massive jejunal bleeding and disseminated intravascular coagulation were identified at the time of the first examination, and the patient died of multiorgan failure 26 days after the embolization. On the basis of our experience, we established an effective treatment strategy for HD patients with acute nonvariceal massive GIB, by immediately identifying the exact site and degree of bleeding using contrast-enhanced computed tomography and performing early treatment with transarterial embolization.

  4. Compound list: carboplatin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available carboplatin CBP 00133 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/carboplatin....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/carboplatin...T/Rat/in_vivo/Liver/Repeat/carboplatin.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bio...sciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/carboplatin.Rat.in_vivo.Kidney.Single.zi...p ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Kidney/Repeat/carboplatin.Rat.in_vivo.Kidney.Repeat.zip ...

  5. Comparison of classification methods for voxel-based prediction of acute ischemic stroke outcome following intra-arterial intervention

    Science.gov (United States)

    Winder, Anthony J.; Siemonsen, Susanne; Flottmann, Fabian; Fiehler, Jens; Forkert, Nils D.

    2017-03-01

    Voxel-based tissue outcome prediction in acute ischemic stroke patients is highly relevant for both clinical routine and research. Previous research has shown that features extracted from baseline multi-parametric MRI datasets have a high predictive value and can be used for the training of classifiers, which can generate tissue outcome predictions for both intravenous and conservative treatments. However, with the recent advent and popularization of intra-arterial thrombectomy treatment, novel research specifically addressing the utility of predictive classi- fiers for thrombectomy intervention is necessary for a holistic understanding of current stroke treatment options. The aim of this work was to develop three clinically viable tissue outcome prediction models using approximate nearest-neighbor, generalized linear model, and random decision forest approaches and to evaluate the accuracy of predicting tissue outcome after intra-arterial treatment. Therefore, the three machine learning models were trained, evaluated, and compared using datasets of 42 acute ischemic stroke patients treated with intra-arterial thrombectomy. Classifier training utilized eight voxel-based features extracted from baseline MRI datasets and five global features. Evaluation of classifier-based predictions was performed via comparison to the known tissue outcome, which was determined in follow-up imaging, using the Dice coefficient and leave-on-patient-out cross validation. The random decision forest prediction model led to the best tissue outcome predictions with a mean Dice coefficient of 0.37. The approximate nearest-neighbor and generalized linear model performed equally suboptimally with average Dice coefficients of 0.28 and 0.27 respectively, suggesting that both non-linearity and machine learning are desirable properties of a classifier well-suited to the intra-arterial tissue outcome prediction problem.

  6. Intra-Arterially Delivered Mesenchymal Stem Cells Are Not Detected in the Brain Parenchyma in an Alzheimer's Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Na Kyung Lee

    Full Text Available Mesenchymal stem cells (MSCs have a promising role as a therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD. Prior studies suggested that intra-arterially administered MSCs are engrafted into the brain in stroke or traumatic brain injury (TBI animal models. However, a controversial standpoint exists in terms of the integrity of the blood brain barrier (BBB in transgenic AD mice. The primary goal of this study was to explore the feasibility of delivering human umbilical cord-blood derived mesenchymal stem cells (hUCB-MSCs into the brains of non-transgenic WT (C3H/C57 and transgenic AD (APP/PS1 mice through the intra-arterial (IA route. Through two experiments, mice were infused with hUCB-MSCs via the right internal carotid artery and were sacrificed at two different time points: 6 hours (experiment 1 or 5 minutes (experiment 2 after infusion. In both experiments, no cells were detected in the brain parenchyma while MSCs were detected in the cerebrovasculature in experiment 2. The results from this study highlight that intra-arterial delivery of MSCs is not the most favorable route to be implemented as a potential therapeutic approach for AD.

  7. Intra-Arterially Delivered Mesenchymal Stem Cells Are Not Detected in the Brain Parenchyma in an Alzheimer's Disease Mouse Model.

    Science.gov (United States)

    Lee, Na Kyung; Yang, Jehoon; Chang, Eun Hyuk; Park, Sang Eon; Lee, Jeongmin; Choi, Soo Jin; Oh, Wonil; Chang, Jong Wook; Na, Duk L

    2016-01-01

    Mesenchymal stem cells (MSCs) have a promising role as a therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). Prior studies suggested that intra-arterially administered MSCs are engrafted into the brain in stroke or traumatic brain injury (TBI) animal models. However, a controversial standpoint exists in terms of the integrity of the blood brain barrier (BBB) in transgenic AD mice. The primary goal of this study was to explore the feasibility of delivering human umbilical cord-blood derived mesenchymal stem cells (hUCB-MSCs) into the brains of non-transgenic WT (C3H/C57) and transgenic AD (APP/PS1) mice through the intra-arterial (IA) route. Through two experiments, mice were infused with hUCB-MSCs via the right internal carotid artery and were sacrificed at two different time points: 6 hours (experiment 1) or 5 minutes (experiment 2) after infusion. In both experiments, no cells were detected in the brain parenchyma while MSCs were detected in the cerebrovasculature in experiment 2. The results from this study highlight that intra-arterial delivery of MSCs is not the most favorable route to be implemented as a potential therapeutic approach for AD.

  8. Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: Seven cases

    Institute of Scientific and Technical Information of China (English)

    Kiminori Uka; Kazuaki Chayama; Hiroshi Aikata; Shintaro Takaki; Tomokazu Kawaoka; Hiromi Saneto; Daiki Mild; Shoichi Takahashi; Naoyuld Toyota; Katsuhide Ito

    2008-01-01

    The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC).Systemic gemcitabine chemotherapy seems effective in many cancers.We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP).Seven patients with non-resectable advanced HCC were treated with GEMFP.One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on day z, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port.Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8.The objective response was 57%.The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients),and progressive disease (no patients).The median survival period was 8 mo (range, 5-55).With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%),seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia,respectively.GEMFP may potentially be effective for nonresectable advanced HCC, but it has severe hematologic toxicity.

  9. Selection of patients for intra-arterial treatment for acute ischaemic stroke : Development and validation of a clinical decision tool in two randomised trials

    NARCIS (Netherlands)

    E. Venema (Esmee); M.J.H.L. Mulder (Maxim); B. Roozenbeek (Bob); J.P. Broderick (Joseph P.); S.D. Yeatts (Sharon D.); P. Khatri (Pooja); O.A. Berkhemer (Olvert); B.J. Emmer (Bart J.); Y.B.W.E.M. Roos (Yvo); C.B. Majoie (Charles); R.J. Van Oostenbrugge; W.H. van Zwam (Wim); A. van der Lugt (Aad); E.W. Steyerberg (Ewout); D.W.J. Dippel (Diederik); H.F. Lingsma (Hester)

    2017-01-01

    markdownabstract__Objective__ To improve the selection of patients with acute ischaemic stroke for intra-arterial treatment using a clinical decision tool to predict individual treatment benefit. __Design__ Multivariable regression modelling with data from two randomised controlled clinical

  10. Intra-arterial thrombolysis with r-tPA for the treatment of acute cerebral infarction 6 to 9 hours after onset

    Institute of Scientific and Technical Information of China (English)

    毕敏

    2013-01-01

    Objective To determine the safety and efficacy of intra-arterial recombinant tissue plasminogen activator(r-tPA)for the treatment of acute cerebral infarction(ACI)in patients under the guidance of computed

  11. Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Stem Cells in Subacute Ischemic Stroke Patients.

    Science.gov (United States)

    Ghali, Azza Abass; Yousef, Mohamed Khalil; Ragab, Osama AbdAllah; ElZamarany, Enas Arafa

    2016-01-01

    Based on many preclinical and small clinical trials, stem cells can help stroke patient with the possibility of replacing the cells and supporting the remaining cells. The aim of this study was to evaluate the safety and feasibility of bone marrow mononuclear (BMMN) stem cell transplantation in subacute ischemic stroke patients. Thirty-nine (n = 39) patients with subacute ischemic cerebral infarct due to large artery occlusion in the middle cerebral artery (MCA) territory were recruited. They were distributed into two groups: first group (n = 21) served as an experimental group, which received intra-arterial (IA) mononuclear stem cells (bone marrow-derived mononuclear cell), while the other group (n = 18) served as a control group. All the patients were evaluated clinically by National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel Index, modified and standardized Arabic version of the Comprehensive Aphasia Test, and radiological for 12 months. The stem cell-treated group showed better improvement, but it was not significant when compared with the non-treated group. The volume of infarction changes at the end of the study was non-significant between both the groups. There was no, or minimal, adverse reactions in stem cell-treated group. The study results suggest that autologous BMMN stem cell IA transplantation in subacute MCA ischemic stroke patients is safe with very minimal hazards, but no significant improvement of motor, language disturbance, or infarction volume was detected in stem cell-treated group compared with the non-treated group.

  12. Feeding Arteries of Primary Tongue Cancers on Intra-arterial Infusion Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kamitani, Takeshi, E-mail: kamitani@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan); Kawanami, Satoshi, E-mail: kawanami-01@mac.com [Kyushu University, Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences (Japan); Asayama, Yoshiki, E-mail: asayama@radiol.med.kyushu-u.ac.jp; Matsuo, Yoshio, E-mail: yymatsuo@radiol.med.kyushu-u.ac.jp; Yonezawa, Masato, E-mail: ymasato@radiol.med.kyushu-u.ac.jp; Yamasaki, Yuzo, E-mail: yyama@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan); Nagao, Michinobu, E-mail: minagao@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences (Japan); Yamanouchi, Torahiko, E-mail: tora0228@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan); Yabuuchi, Hidetake, E-mail: h-yabu@med.kyushu-u.ac.jp [Kyushu University, Department of Health Sciences, Graduate School of Medical Sciences (Japan); Nakamura, Katsumasa, E-mail: nakam@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan); Nakashima, Torahiko, E-mail: nakatora@qent.med.kyushu-u.ac.jp [Kyushu University, Department of Otorhinolaryngology, Graduate School of Medical Sciences (Japan); Honda, Hiroshi, E-mail: honda@radiol.med.kyushu-u.ac.jp [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences (Japan)

    2016-02-15

    PurposeTo evaluate the frequency and the predictive factor of each feeding artery on intra-arterial infusion chemotherapy (IAIC) in primary tongue cancer.Materials and MethodsWe retrospectively evaluated 20 patients who received IAIC for primary tongue cancer. The main and accompanying feeding arteries were identified on super-selective angiography of the branches of the external carotid artery. Tumor diameter, and extension to the contralateral side, tongue extrinsic muscles (TEMs), and lateral mesopharyngeal wall were determined based on magnetic resonance imaging or computed tomography findings.ResultsThe main feeding artery was the ipsilateral lingual artery (LA) in 15 of the 20 examined tumors and the contralateral LA in the other 5. Ten cancers had only one feeding artery, and multiple feeding arteries were detected in the remaining 10. Tumors >4 cm (n = 9), those with extension to the contralateral side (n = 13), and those with extension to TEMs (n = 15) were supplied by significantly larger numbers of feeding arteries compared to tumors without these features (P = 0.01, 0.049, and 0.02, respectively). The frequency of feeding from the contralateral LA was 64 % (9/14) and 17 % (1/6) in tumors with and without extension to the contralateral side, respectively. Feeding from a facial artery (FA) was not detected in tumors ≤4 cm, while 5 of the 9 (56 %) tumors >4 cm were supplied by a FA (P = 0.01).ConclusionA careful search for feeding arteries is required, especially in large tumors with extension to the contralateral side or to TEMs.

  13. Radiation dose reduction in intra-arterial chemotherapy infusion for intraocular retinoblastoma.

    Science.gov (United States)

    Cooke, Daniel L; Stout, Charles E; Kim, Warren T; Hetts, Steven W; Higashida, Randall T; Halbach, Van V; Dowd, Christopher F; Gould, Robert G

    2014-12-01

    Retinoblastoma (RB) is a rare malignancy affecting the pediatric population. Intravenous chemotherapy is the longstanding delivery method, although intra-arterial (IA) chemotherapy is gaining popularity given the reduced side effects compared with systemic chemotherapy administration. Given the sensitivity of the target organ, patient age, and secondary tumor susceptibility, a premium has been placed on minimizing procedural related radiation exposure. To reduce patient x-ray dose during the IA infusion procedure, customized surgical methods and fluoroscopic techniques were employed. The routine fluoroscopic settings were changed from the standard 7.5 pulses/s and dose level to the detector of 36 nGy/pulse, to a pulse rate of 4 pulses/s and detector dose to 23 nGy/pulse. The angiographic dose indicators (reference point air kerma (Ka) and fluoroscopy time) for a cohort of 10 consecutive patients (12 eyes, 30 infusions) were analyzed. An additional four cases (five eyes, five infusions) were analyzed using dosimeters placed at anatomic locations to reflect scalp, eye, and thyroid dose. The mean Ka per treated eye was 20.1±11.9 mGy with a mean fluoroscopic time of 8.5±4.6 min. Dosimetric measurements demonstrated minimal dose to the lens (0.18±0.10 mGy). Measured entrance skin doses varied from 0.7 to 7.0 mGy and were 73.4±19.7% less than the indicated Ka value. Ophthalmic arterial melphalan infusion is a safe and effective means to treat RB. Modification to contemporary fluoroscopic systems combined with parsimonious fluoroscopy can minimize radiation exposure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Intra-arterial tirofiban infusion for thromboembolic complication during coil embolization of ruptured intracranial aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Dae, E-mail: aronnn@naver.com [Department of Radiology, Seoul National University Boramae Medical Center, Seoul National University College of Medicine, 425 Sindaebang-dong, Dongjak-gu, Seoul 156-707 (Korea, Republic of); Lee, Jong Young, E-mail: gen78@naver.com [Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744 (Korea, Republic of); Seo, Jung Hwa, E-mail: jhseo34@gmail.com [Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744 (Korea, Republic of); Kang, Hyun-Seung, E-mail: hsk4428@yahoo.com [Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744 (Korea, Republic of); Kim, Jeong Eun, E-mail: eunkim@snu.ac.kr [Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744 (Korea, Republic of); Jung, Keun Hwa, E-mail: jungkh@gmail.com [Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744 (Korea, Republic of); Han, Moon Hee, E-mail: hanmh@snuh.org [Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744 (Korea, Republic of); Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744 (Korea, Republic of)

    2012-10-15

    Introduction: Intra-arterial (IA) thrombolytic intervention for acute thrombosis has been challenged due to the risk of bleeding during the endovascular treatment of ruptured aneurysms. We present the results of IA tirofiban infusion for thromboembolic complications during coil embolization in patients with ruptured intracranial aneurysms. Methods: Thromboembolic events requiring thrombolytic intervention occurred in 39 (10.5%) cases during coil embolization of 372 consecutive ruptured intracranial aneurysms. Maximal aneurysm diameters of 39 patients (mean age, 54.7 ± 13.2 years; 23 female, 16 male) ranged from 2.1 to 13.1 mm (mean, 6.6 ± 3.0 mm). The anterior communicating artery was the most common site (n = 13), followed by the middle cerebral artery (n = 9) and the posterior communicating artery (n = 7). In this series, we used intracranial stents in 10 patients during the procedure. Superselective IA tirofiban infusion through a microcatheter was performed to resolve thrombi and emboli. We assessed the efficacy and safety of IA tirofiban infusion in patients with ruptured aneurysms. Results: Intraarterially administered tirofiban doses ranged from 0.25 to 1.25 mg (mean, 0.71 ± 0.26 mg). Effective thrombolysis or recanalization was achieved in 34 patients (87.2%), and three patients (7.7%) suffered distal migration of clots with partial recanalization. The rest (5.1%) had no recanalization. Nonconsequent intracerebral hemorrhage occurred in two patients (5.1%) after the procedure. Thromboemboli-related cerebral infarction developed in eight patients, and only two patients remained infarction related disabilities. Conclusion: IA tirofiban infusion seems to be efficacious and safe for thrombolysis during coil embolization in patients with ruptured intracranial aneurysms.

  15. Intravenous versus intra-arterial thrombolysis in ischemic stroke: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qing-feng Ma

    Full Text Available Reperfusion following ischemic stroke can be attained by either intravenous thrombolysis (IVT or intra-arterial thrombolysis (IAT. Only a limited number of randomized prospective studies have compared the efficacy and safety of IVT and IAT. This meta-analysis investigated possible clinical benefits of IAT relative to IVT in patients with acute ischemic stroke.We searched the PubMed, Cochrane, and Google Scholar databases through October 2013 for manuscripts that describe the findings of randomized controlled or prospective studies that evaluated the outcomes of patients with ischemic stroke who were treated with IVT or IAT. The clinical outcome measures were score on the modified Rankin scale (mRS and mortality at 90 days. A favorable outcome was defined as an mRS score of 0 to 2.For the mRS, the combined odds ratio (OR of 3.28 (95% confidence interval (CI, 1.91 to 5.65, P < 0.001 indicated that patients who received IAT had a significantly higher chance for a favorable outcome than did those who received IVT. For mortality, the OR indicated that IAT therapy significantly reduced the proportion of patients who died within 90 days of the procedure (combined OR, 0.40; 95%CI, 0.17 to 0.92; P = 0.032.This meta-analysis determined that IAT conferred a significantly greater probability of achieving a favorable outcome compared with IVT. There was also a significant difference in mortality rates between IAT and IVT. The studies included in this analysis were small and heterogeneous; therefore, larger randomized prospective clinical studies are necessary to further investigate this issue.

  16. The effects of low dose chemotherapy for advanced hepatocellular carcinoma through percutaneously implanted intra-arterial port system

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Seok; Won, Je Hwan; Yoo, Byung Moo; Kim, Young Soo; Cho, Sung Won [Ajou Univ. College of Medicine, Suwon (Korea, Republic of); Park, Dong Won [Suwon Medical Center, Suwon (Korea, Republic of)

    2001-07-01

    To investigate the effects of low-dose FP (5-Fluorouracil[5FU]+Cispatin[CDDP]) therapy through a percutaneously implanted intra-arterial port system in patients with advanced hepatocellular carcinoma (HCC). Twenty-five patients with advanced HCCs and portal vein thrombosis, or large HCCs which were unresectable or for which transarterial chemoembolization was thought to be ineffective, underwent intra-arterial port implantation. The mean maxinal diameter of these tumors was 13.7 (range, 5-21.5) cm, and they were located at the right lobe (n=18), the left lobe(n=3), or throughout the liver (n=4). Tumor thrombosis was detected in the main (n=14), right (n=3) and left portal vein(n=1), the right portal vein and inferior vena cava(n=2), and the inferior vena cava(n=1). The four others patients had no portal vein thrombosis. All intra-arterial port implantations were performed percutaneously in the angiographic ward through the right or left common femoral artery. The port chamber was implanted in the inguinal area and fixed using histoacryl. For intra-arterial chemotherapy, 5-FU (250 mg/day) and CDDP (10 mg/day) were used for five days every four weeks. In order to observe changes in tumor size, follow-up CT scanning was performed every two months. Implantation of the port system was successful in all cases, and patients underwent between one and eleven (mena, 3.9) sessions of chemotherapy. Port-and catheter-related complications, namely dislodgement of the catheter(n=2), wound infection(n=2), migration of the coil(n=1) and catheter occlusion(n=1) occurred in six patients (24%), and chemotherapy-related complications, namely liver failure(n=3) and gastric ulcer bleeding(n=1), in four (16%). A complete response, i. e. the disappearance of tumor thrombosis of the portal vein, was achieved in one patient (4%), a partial response in three (12%), and a minor response in four (16%); the overall response rate was 32% and the mean survival period was 7.6 months. Low-dose FP

  17. Trombólise intra-arterial pulmonar no pós-operatório de clipagem de aneurisma cerebral: relato de caso Intra-arterial pulmonary thrombolysis at the postoperative period of brain aneurysm clamping: case report

    Directory of Open Access Journals (Sweden)

    Salomón Soriano Ordinola Rojas

    2008-09-01

    Full Text Available O tromboembolismo pulmonar (TEP é uma importante causa de morbimortalidade nos pacientes submetidos a procedimentos neurocirúrgicos. O objetivo deste estudo foi apresentar um caso de trombólise intra-arterial pulmonar em pós-operatório recente de neurocirurgia. Paciente do sexo masculino, sendo submetido a clipagem de aneurisma de artéria comunicante anterior, apresentou como complicação no sétimo dia de pós-operatório, tromboembolismo pulmonar maciço, apresentando instabilidade hemodinâmica, sendo optado pela trombólise intra-arterial pulmonar com alteplase. Apresentou evolução satisfatória, sem complicações hemorrágicas, recebendo alta hospitalar. O tromboembolismo pulmonar é uma condição com alta morbi-mortalidade no pós-operatório de neurocirurgia, devendo ser a trombólise ser uma alternativa terapêutica nos casos refratários ao tratamento clínico.Pulmonary thromboembolism is a major cause of morbidity and mortality of patients undergoing neurosurgical procedures. The purpose of this study was to present a case of intra-arterial pulmonary thrombolysis in recent neurosurgery postoperative period. Male patient, undergoing neurosurgery, presented as a complication on the seventh day of postoperative massive pulmonary embolism with hemodynamic instability and intraarterial pulmonary thrombolysis with alteplase was indicated. Evolution was satisfactory without bleeding complications and patient was discharged. Pulmonary thromboembolism is a high morbidity and mortality condition at neurosurgical postoperative period and thrombolysis should be an alternative therapy in cases refractory to clinical treatment.

  18. Intra-arterial thrombolysis vs. standard treatment or intravenous thrombolysis in adults with acute ischemic stroke: a systematic review and meta-analysis.

    Science.gov (United States)

    Nam, Julian; Jing, He; O'Reilly, Daria

    2015-01-01

    Recent evidence has suggested that intra-arterial thrombolysis may provide benefit beyond intravenous thrombolysis in ischemic stroke patients. Previous meta-analyses have only compared intra-arterial thrombolysis with standard treatment without thrombolysis. The objective was to review the benefits and harms of intra-arterial thrombolysis in ischemic stroke patients. We undertook a meta-analysis of randomized controlled trials comparing the efficacy and safety of intra-arterial thrombolysis with either standard treatment or intravenous thrombolysis following acute ischemic stroke. Primary outcomes included poor functional outcomes (modified Rankin Scale 3-6), mortality, and symptomatic intracranial hemorrhage. Study quality was assessed, and outcomes were stratified by comparison treatment received. Four trials (n = 351) comparing intra-arterial thrombolysis with standard treatment were identified. Intra-arterial thrombolysis reduced the risk of poor functional outcomes (modified Rankin Scale 3-6) [relative risk (RR) = 0·80; 95% confidence interval = 0·67-0·95; P = 0·01]. Mortality was not increased (RR = 0·82; 95% confidence interval = 0·56-1·21; P = 0·32); however, risk of symptomatic intracranial hemorrhage was nearly four times more likely (RR = 3·90; 95% confidence interval = 1·41-10·76; P = 0·006). Two trials (n = 81) comparing intra-arterial thrombolysis with intravenous thrombolysis were identified. Intra-arterial thrombolysis was not found to reduce poor functional outcomes (modified Rankin Scale 3-6) (RR = 0·68; 95% confidence interval = 0·46-1·00; P = 0·05). Mortality was not increased (RR = 1·12; 95% confidence interval = 0·47-2·68; P = 0·79); neither was symptomatic intracranial hemorrhage (RR = 1·13; 95% confidence interval = 0·32-3·99; P = 0·85). Differences in time from symptom onset-to-treatment and type of thrombolytic administered were found

  19. Impact of Thrombus Length on Outcomes After Intra-Arterial Aspiration Thrombectomy in the THERAPY Trial.

    Science.gov (United States)

    Yoo, Albert J; Khatri, Pooja; Mocco, J; Zaidat, Osama O; Gupta, Rishi; Frei, Donald; Lopes, Demetrius; Shownkeen, Harish; Berkhemer, Olvert A; Meyer, Denise; Hak, Susana S; Kuo, Sophia S; Buell, Hope; Bose, Arani; Sit, Siu Po; von Kummer, Rüdiger

    2017-07-01

    Increasing thrombus length (TL) impedes recanalization after intravenous (IV) thrombolysis. We sought to determine whether the clinical benefit of aspiration thrombectomy relative to IV r-tPA (recombinant tissue-type plasminogen activator) may be greater at longer TL. THERAPY was a randomized trial of aspiration thrombectomy plus IV r-tPA versus IV r-tPA alone in large-vessel stroke patients with prospective TL measurement ≥8 mm. In this post hoc study, we evaluated the association of TL with trial end points and potential endovascular treatment effect, using univariate, multivariable, and multiplicative interaction analyses. TL data were available for all 108 patients (28% internal carotid artery, 62% M1, and 10% M2). Median TL was 14.0 mm (interquartile range, 9.7-19.5 mm). Longer TL was associated with worse outcome (90-day modified Rankin Scale score: odds ratio, 1.24 per 5-mm TL increment; 95% confidence interval, 1.04-1.52; P=0.02), even after adjusting for key outcome predictors (adjusted P=0.004). Longer TL was also associated with more serious adverse events (adjusted P=0.01), more symptomatic hemorrhages (adjusted P=0.03), and increased mortality (adjusted P=0.01). No significant relationship was observed between TL and angiographic reperfusion (modified thrombolysis in cerebral ischemia 2b-3), but greater TL was associated with longer endovascular procedural times (ρ=0.36; P=0.045). Increasing TL was associated with greater aspiration thrombectomy treatment effect (interaction term P=0.03). This might be related to a potentially stronger adverse effect of increasing TL on 90-day modified Rankin Scale for patients treated with IV r-tPA (ρ=0.39; P=0.01) compared with intra-arterial therapy (ρ=0.20; P=0.165). Ischemic stroke patients with longer symptomatic thrombi have worse 90-day clinical outcomes but may have a greater relative benefit of aspiration thrombectomy over IV r-tPA alone. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01429350

  20. Access to the ophthalmic artery by retrograde approach through the posterior communicating artery for intra-arterial chemotherapy of retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Chi-Tuan; Blanc, Raphael; Pistocchi, Silvia; Bartolini, Bruno; Piotin, Michel [Fondation Rothschild Hospital, Department of Interventional Neuroradiology, Paris (France); Lumbroso-Le Rouic, Livia [Institut Curie, Department of Ocular Oncology, Paris (France)

    2012-08-15

    Intra-arterial infusion of chemotherapy into the ophthalmic artery for treatment of retinoblastoma has been realized after catheterization of the internal carotid and temporary balloon occlusion beyond the orifice of the ophthalmic artery, or more recently after superselective canulation of the ophthalmic artery by a microcatheter. The superselective catheterization of the ophthalmic artery could be cumbersome because of the implantation of the ostium on the carotid siphon or because of the tortuosity of the carotid siphon. We report our experience of using a retrograde approach through the posterior communicating artery that allows a more direct angle of access to the origin of the ophthalmic artery. (orig.)

  1. The Smoking Paradox: Impact of Smoking on Recanalization in the Setting of Intra-Arterial Thrombolysis

    Directory of Open Access Journals (Sweden)

    Elena Meseguer

    2014-05-01

    Full Text Available Background: The smoking paradox refers to a better outcome in smokers eligible for thrombolytic treatment in myocardial infarction or ischemic stroke. Recent findings suggest that current smokers may present higher recanalization rates after intravenous (IV thrombolysis with recombinant tissue plasminogen activator (rt-PA. We evaluated the impact of smoking in a consecutive series of patients treated with intra-arterial (IA rt-PA. Methods: We analyzed data collected between April 2007 and December 2012 in our prospective registry. All acute ischemic stroke patients with an arterial occlusion treated by IA rt-PA (± IV, ± thrombectomy were included. Arterial status was monitored with conventional angiography during the IA procedure. The primary study outcome was a complete recanalization achieved immediately after termination of IA rt-PA infusion. Secondary outcomes included complete recanalization after the end of the endovascular therapy (including complete recanalization achieved after adjunctive thrombectomy, favorable outcome (90-day modified Rankin Score ≤2, 90-day all-cause mortality, and any intracerebral hemorrhage. Results: Among the 227 included patients, 18.5% (n = 42 were current smokers and 16.7% (n = 38 former smokers. Compared with nonsmokers, current smokers were younger, more often men, had less frequently hypertension, and cardioembolic etiology, whereas former smokers were more often men and had more frequently hypercholesterolemia. The rate of complete recanalization was 30% (n = 68 after IA rt-PA infusion and 49% after adjunctive thrombectomy. A higher complete recanalization rate was found both in current smokers (45.2% and former smokers (42.1% compared to nonsmokers (22.5%. After adjustment for potential confounders, the adjusted odds ratio (OR for complete recanalization associated with ever-smokers was 2.51 [95% confidence interval (CI 1.26-4.99; p = 0.009]. A similar adjusted OR was found when the complete

  2. Intra-arterial transplantation of low-dose stem cells provides functional recovery without adverse effects after stroke.

    Science.gov (United States)

    Fukuda, Yuhtaka; Horie, Nobutaka; Satoh, Katsuya; Yamaguchi, Susumu; Morofuji, Youichi; Hiu, Takeshi; Izumo, Tsuyoshi; Hayashi, Kentaro; Nishida, Noriyuki; Nagata, Izumi

    2015-04-01

    Cell transplantation therapy for cerebral infarction has emerged as a promising treatment to reduce brain damage and enhance functional recovery. We previously reported that intra-arterial delivery of bone marrow mesenchymal stem cells (MSCs) enables superselective cell administration to the infarct area and results in significant functional recovery after ischemic stroke in a rat model. However, to reduce the risk of embolism caused by the transplanted cells, an optimal cell number should be determined. At 24 h after middle cerebral artery occlusion and reperfusion, we administered human MSCs (low dose: 1 × 10(4) cells; high dose: 1 × 10(6) cells) and then assessed functional recovery, inflammatory responses, cell distribution, and mortality. Rats treated with high- or low-dose MSCs showed behavioral recovery. At day 8 post-stroke, microglial activation was suppressed significantly, and interleukin (IL)-1β and IL-12p70 were reduced in both groups. Although high-dose MSCs were more widely distributed in the cortex and striatum of rats, the degree of intravascular cell aggregation and mortality was significantly higher in the high-dose group. In conclusion, selective intra-arterial transplantation of low-dose MSCs has anti-inflammatory effects and reduces the adverse effects of embolic complication, resulting in sufficient functional recovery of the affected brain.

  3. Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

    Directory of Open Access Journals (Sweden)

    Fiorentini Giammaria

    2006-01-01

    Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

  4. Clinical experience of intra-arterial therapy in patients with acute ischemic stroke from a single institute

    Energy Technology Data Exchange (ETDEWEB)

    Park, So Young [Dept. Neurology, Seoul National University-Seoul Metropolitan Government Boramae Medical Center, Seoul (Korea, Republic of); Lee, Han Bin; Kim, Jong Guk; Oh, Seung Hun; Kim, Jin Kwon; Kim, Sang Heum; Kim, Ok Joon [CHA Bundang Medical Center, CHA University, Seongnam (Korea, Republic of); Kim, Nam Keun [Institute for Clinical Research, School of Medicine, CHA University, Seongnam (Korea, Republic of)

    2016-11-15

    To compare the efficacy and safety between intra-arterial therapy (IAT) and intra-venous and intra-arterial combined therapy (IVIACT) in patients with acute ischemic stroke in the anterior circulation territory. Forty-one patients treated with IAT using Solitaire were retrospectively reviewed. Nineteen patients were treated with IAT, twenty-two patients were treated with IVIACT, and ten patients of the forty-one patients were managed with multimodal treatment like stent, balloon angioplasty etc. We investigated the rate of recanalization and hemorrhage, NIH stroke scale and 3-month modified Rankin Scale. The overall recanalization rate was 93% and symptomatic ICH occurred in 10% of the patients. There was no difference in hemorrhage, recanalization rate, and early improvement between IAT and IVIACT. Good outcome was more frequently observed in 59% of the patients with IVIACT than 36% of the patients treated with IAT without any significant difference. The patients managed with multimodal treatment did not show any significant hemorrhage outcome. IAT using Solitaire is a useful treatment method without high risk in patients with acute ischemic stroke in the anterior circulation territory. Also, IVIACT and multimodal treatment might be considered as reasonable therapeutic options in these patients.

  5. Continuous Selective Intra-Arterial Application of Nimodipine in Refractory Cerebral Vasospasm due to Aneurysmal Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Stephanie Ott

    2014-01-01

    Full Text Available Background. Cerebral vasospasm is one of the leading courses for disability in aneurysmal subarachnoid hemorrhage. Effective treatment of vasospasm is therefore one of the main priorities for these patients. We report about a case series of continuous intra-arterial infusion of the calcium channel antagonist nimodipine for 1–5 days on the intensive care unit. Methods. In thirty patients with aneurysmal subarachnoid hemorrhage and refractory vasospasm continuous infusion of nimodipine was started on the neurosurgical intensive care unit. The effect of nimodipine on brain perfusion, cerebral blood flow, brain tissue oxygenation, and blood flow velocity in cerebral arteries was monitored. Results. Based on Hunt & Hess grades on admission, 83% survived in a good clinical condition and 23% recovered without an apparent neurological deficit. Persistent ischemic areas were seen in 100% of patients with GOS 1–3 and in 69% of GOS 4-5 patients. Regional cerebral blood flow and computed tomography perfusion scanning showed adequate correlation with nimodipine application and angiographic vasospasm. Transcranial Doppler turned out to be unreliable with interexaminer variance and failure of detecting vasospasm or missing the improvement. Conclusion. Local continuous intra-arterial nimodipine treatment for refractory cerebral vasospasm after aSAH can be recommended as a low-risk treatment in addition to established endovascular therapies.

  6. Treatment of malignant digestive tract obstruction by combined intraluminal stent installation and intra-arterial drug infusion

    Institute of Scientific and Technical Information of China (English)

    Ai-Wu Mao; Zhong-Du Gao; Jia-Yu Xu; Ren-Jie Yancg; Xiang-Seng Xiao; Ting-Hui Jiang; Wei-Jun Jiang

    2001-01-01

    AIM To study the palliative treatment of malignant obstrution of digestive tract with placement of intraluminal stent combined with intra-arterial infusion of chemotherapeutic drugs. METHODS A total of 281 cases of digestive tract malignant obstruction were given per oral (esophagus,stomach, duodenum and jejunum), per anal (colon and rectum ) and percutaneous transhepatic ( biliary )installation of metallic stent. Among them, 205 cases received drug infusion by cannulation of tumor supplying artery with Seldingers technique. RESULTS Altogether 350 stents were installed in 281 cases, obstructive symptoms were relieved or ameliorated after installation. Occurrence of restenotic obstruction was 8 - 43 weeks among those with intraarterial drug infusion, which was later than 4 - 26 weeks in the group with only stent installation. The average survival time of the former group was 43 (3 - 105) weeks,which was significantly longer than 15 (3- 24) weeks of the latter group. CONCLUSION Intraluminal placement of stent combined with intra-arterial infusion chemotherapy is one of the effective palliative therapies for malignant obstruction of the digestive tract with symptomatic as well as etiological treatment.

  7. Comparison of Intra-arterial and Subcutaneous Testicular Hyaluronidase Injection Treatments and the Vascular Complications of Hyaluronic Acid Filler.

    Science.gov (United States)

    Wang, Muyao; Li, Wei; Zhang, Yan; Tian, Weidong; Wang, Hang

    2017-02-01

    Hyaluronidase is a key preventative treatment against vascular complications of hyaluronic acid (HA) filler injection, but the degradation profile of HA to hyaluronidase is limited, and the comparison between intra-arterial and subcutaneous injections of hyaluronidase has not been studied. To evaluate HA degradation to hyaluronidase and compare different treatments between intra-arterial and subcutaneous testicular hyaluronidase injections. The authors observed HA degradation to hyaluronidase in vitro via microscopic examination and particle analysis. Rabbit ears were used for the in vivo study. There were 2 control groups receiving ligation or HA-induced embolism in the arteries, respectively, and 2 intervention groups receiving hyaluronidase treatments in different regions. The laser Doppler blood perfusion monitoring measurements were made at defined time points, and biopsies were taken on Day 2. Nearly, all of the HAs degraded in vitro at the 1-hour time point. Subcutaneous hyaluronidase treatment showed better recovery of blood perfusion. Histology showed severe inflammation in the embolism group and mild inflammation in the intervention groups. A complete enzymatic degradation of HA filler to hyaluronidase needs a certain time, and subcutaneous hyaluronidase treatment may be the better option.

  8. Clinical outcome after intra-arterial stroke therapy in the very elderly: why is it so heterogeneous?

    Directory of Open Access Journals (Sweden)

    Ronil V. Chandra

    2014-04-01

    Full Text Available Very elderly patients (i.e. ≥80 years are disproportionally affected by acute ischemic stroke. They account for a third of hospital stroke admissions, but two thirds of overall stroke-related morbidity and mortality. There is some evidence of clinical benefit in treating selected very elderly patients with intravenous thrombolytic therapy (IVT. For very elderly patients ineligible or non-responsive to IVT, intra-arterial therapy (IAT may have promise in improving clinical outcome. However, its unequivocal efficacy in the general population remains to be proven in randomized trials. Small cohort studies reveal that the rate of good clinical outcome for very elderly patients after IAT is highly variable, ranging from 2% to 28%. In addition, they experience higher rates of futile reperfusion than younger patients. Thus it is imperative to understand the factors that impact on clinical outcome in very elderly patients after IAT. The aim of this review is to examine the factors that may be responsible for the heterogeneous clinical response of the very elderly to IAT. This will allow the reader to integrate the current available evidence to individualize intra-arterial stroke therapy in very elderly patients. Placing emphasis on pre-stroke independent living, smaller infarct core size, short procedure times, and avoiding general anesthesia where feasible, will help improve rates of good clinical outcome.

  9. Combined intra-arterial thrombolysis and neuprotectant agents reduce cerebral infarction in rabbits with experimental acute cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Pei Shi

    2006-01-01

    BACKGROUND:The intra-arterial thrombolytic therapy is one of main methods for more patients to obtain bene-fits.The percentage of arterial recanalization treated with intre-arterial therapy is higher than with intra-venous therapy.next,the dose of thrombolytic medicines is lower and the therapeutic time window may be possibly longer.Related researches are focus on intra-artedal thrombolysis combining with neuprotectant agents to treat acute ischemic stroke.The results show that combination of them can further prolong the therapeutic time window.improve the percentage of arterial recanalization and reduce cerebral infarction volume.OBJECTIVE:To observe the effect of single thmmbolitic therapy combined with neuroprotectant agents in the treatment of acute ischemic stroke.DESIGN:Randomized block design.SETTING:Xinhua Hospital of Xixiang City.Henan Province.MATERIALS:Thirty-six adult male white rabbits.weighing 1.5-2.0 kg.dean grade.were provided by Expedmental Animal Center of Xinxiang Medical College.All rabbits were randomly divided into three groups:intra-arterial thrombolysis control group.corenalin control group and combination group with 12 in each group.Urekinase was provided by Beijing Saisheng Pharmaceutical Co.,Ltd.(batch number:020923);corenalin by Sanjing Pharmaceutical Co.,Ltd.of Harbin Pharmacautical Group(batch number:021106):nimodipine by Shandong Xihua Pharmaceutical Co.,Ltd.(batch number:020611):contrast medium IOPAMlR0300 by Bracco s.P.a.Milano italian (batch number:0584);2,3,5-triphenyltetrazolium chloride(TTC)by Beijing Mashi Fine ChemicaL Product Co.,Ltd.(batch number:020926).METHODS: The experiment was camed out in the Department of Intervention. Second People's Hospital of Xinxiang from September 2002 to May 2003.①According to techniques of Benes et al and Zhu et al,animal models with acute ischemia were established.Two hours later.the therapy began.Intra-artedal thrombolysis control group:5 000 U/kg urokinase was dripped in Ieft common

  10. Successful Treatment of Two Cases of Squamous Cell Carcinoma on the Ear with Intra-Arterial Administration of Peplomycin through a Superficial Temporal Artery

    Directory of Open Access Journals (Sweden)

    Takahiro Haga

    2014-09-01

    Full Text Available Cutaneous squamous cell carcinoma (SCC is the second most common non-melanoma skin cancer and tends to develop in sun-exposed cosmetic areas, including the ear. In this report, we describe two cases of SCC on the ear successfully treated with intra-arterial administration of peplomycin through a superficial temporal artery. In addition to this selective chemotherapy, we administered oral tegafur, which achieved complete remission of the tumor. These findings suggest that intra-arterial administration of peplomycin with tegafur is one of the optimal therapies for the treatment of SCC developing on the ear.

  11. Effects of the intra-arterial injection of bradykinin into the limbs, upon the activity of mesencephalic reticular units.

    Science.gov (United States)

    Lombard, M C; Guilbaud, G; Besson, J M

    1975-02-01

    The changes in firing rate of mesencephalic reticular units after intra-arterial injection into the limbs of a potent nociceptive agent, bradykinin, were studied in cats (unanesthetized, immobilized with flaxedil and hyperventilated). 30 per cent of the d35 studied cells were affected, 56 per cent were excited, 23 per cent inhibited and 5 per cent had mixed effects. Among the 75 excited cells, the activation of 16 of them seemed to related to the arousa- processes (group A); for 56 cells the increase seemed dire-tly dependent on the nociceptive stimulation itself (group B). The changes of firing rate were repruducible; their latencies and durations were of the same order as the latencies and duration of the nociceptive reactions and painful sensation s, which have been obtained in animals and men after bradykinin injections. The modifications induced by bradykinin administration were suppressed by Ketamin and Thiopental.

  12. Intra-arterial vasodilators to prevent radial artery spasm: a systematic review and pooled analysis of clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Kwok, Chun Shing, E-mail: shingkwok@doctors.org.uk [Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent (United Kingdom); Rashid, Muhammad [St. Helens & Knowsley Teaching Hospital (NHS) Trust, Whiston Hospital, Prescot (United Kingdom); Fraser, Doug [Manchester Heart Centre, Manchester Royal Infirmary (United Kingdom); Nolan, James [University Hospital of North Midlands, Stoke-on-Trent (United Kingdom); Mamas, Mamas [Keele Cardiovascular Research Group, Keele University, Stoke-on-Trent (United Kingdom); Farr Institute, Institute of Population Health, University of Manchester, Manchester (United Kingdom)

    2015-12-15

    Objectives: The aim of this study is to review the available literature on the efficacy and safety of agents used for prevention of RAS. Background: Different vasodilator agents have been used to prevent radial artery spasm (RAS) in patients undergoing transradial cardiac catheterization. Methods: We included studies that evaluated any intra-arterial drug administered in the setting cardiac catheterization that was undertaken through the transradial access site (TRA). We also compared studies for secondary outcomes of major bleeding, procedure time, and procedure failure rate in setting of RAS prevention, patent hemostasis and radial artery occlusion. Results: 22 clinical studies met the inclusion criteria. For placebo, RAS rate was 12% (4 studies, 638 participants), which was similar to 2.5 mg of verapamil 12% (3 studies, 768 participants) but greater than 5 mg of verapamil (4%, 2 studies, 497 participants). For nicorandil, there was a much higher RAS rate compared to placebo (16%, 3 studies, 447 participants). The lowest rates of RAS was found for nitroglycerin at both 100 μg (4%) and 200 μg (2%) doses, isosorbide mononitrate (4%) and nicardipine (3%). We found no information regarding the procedure failure rates, patent hemostasis, and radial artery occlusion in these studies. Conclusions: In this largest and up-to-date review on intra-arterial vasodilators use to reduce RAS, we have found that the verapamil at a dose of 5 mg or verapamil in combination with nitroglycerine are the best combinations to reduce RAS. - Highlights: • Radial artery spasm (RAS) causes procedural failure in transradial catheterization. • RAS may complicate 10–15% procedures undertaken through the radial approach. • We reviewed the efficacy of vasodilators that have been used to minimize RAS. • The pooled RAS rate was lowest with 5 mg of verapamil (4%) compared to placebo (12%). • The best combination of drugs to minimize RAS is nitroglycerine and verapamil.

  13. Selective intra-arterial administration of {sup 18}F-FDG to the rat brain - effects on hemispheric uptake

    Energy Technology Data Exchange (ETDEWEB)

    Arnberg, Fabian; Samen, Erik; Lundberg, Johan; Grafstroem, Jonas; Soederman, Michael; Stone-Elander, Sharon; Holmin, Staffan [Karolinska Institutet, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska University Hospital-Solna, Department of Neuroradiology, Stockholm (Sweden); Lu, Li [Karolinska University Hospital-Solna, KERIC, Stockholm (Sweden)

    2014-05-15

    The purpose of this study was to investigate the radioligand uptake and iodine contrast distribution in the intra- and extracranial circulation of the rat, after intra-arterial injections to the common carotid artery and different parts of the internal carotid artery. All animal experiments were carried out in accordance with Karolinska Institutet's guidelines and were approved by the local laboratory animal ethics committee. We used clinical neurointerventional systems to place microcatheters in the extra- or intracranial carotid artery of 15 Sprague-Dawley rats. Here, injection dynamics of iodine contrast was assessed using digital subtraction angiography. Maintaining the catheter position, the animals were placed in a micro PET and small-animal positron emission tomography (PET) was used to analyze injections [2-{sup 18}F]-2-fluoro-2-deoxy-d-glucose ({sup 18}F-FDG). Microcatheters had to be placed in the intracranial carotid artery (iICA) for the infusate to distribute to the brain. Selective injection via the iICA resulted in a 9-fold higher uptake of {sup 18}F-FDG in the injected hemisphere (p < 0.005) compared to both intravenous and more proximal carotid artery injections. Furthermore, selective injection gave a dramatically improved contrast between the brain and extracranial tissue. Intra-arterial injection increases the cerebral uptake of a radiotracer dramatically compared to systemic injection. This technique has potential applications for endovascular treatment of malignancies allowing intra-interventional modifications of injection strategy, based on information on tumor perfusion and risk to surrounding normal parenchyma. Furthermore the technique may increase diagnostic sensitivity and avoid problems due to peripheral pharmacological barriers and first passage metabolism of labile tracers. (orig.)

  14. Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won Tae; Kim, Yong Kan; Lee, Ju Hye; Kim, Dong Hyun; Park, Dahl; Cho, Kyu Sup; Kim, Dong Won [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Nam, Ji Ho; Roh, Hwan Jung [Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2013-09-15

    The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery. Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m2) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT. At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence. Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens.

  15. Value of Computed Tomographic Perfusion-Based Patient Selection for Intra-Arterial Acute Ischemic Stroke Treatment.

    Science.gov (United States)

    Borst, Jordi; Berkhemer, Olvert A; Roos, Yvo B W E M; van Bavel, Ed; van Zwam, Wim H; van Oostenbrugge, Robert J; van Walderveen, Marianne A A; Lingsma, Hester F; van der Lugt, Aad; Dippel, Diederik W J; Yoo, Albert J; Marquering, Henk A; Majoie, Charles B L M

    2015-12-01

    The utility of computed tomographic perfusion (CTP)-based patient selection for intra-arterial treatment of acute ischemic stroke has not been proven in randomized trials and requires further study in a cohort that was not selected based on CTP. Our objective was to study the relationship between CTP-derived parameters and outcome and treatment effect in patients with acute ischemic stroke because of a proximal intracranial arterial occlusion. We included 175 patients who underwent CTP in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN). Association of CTP-derived parameters (ischemic-core volume, penumbra volume, and percentage ischemic core) with outcome was estimated with multivariable ordinal logistic regression as an adjusted odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale. Interaction between CTP-derived parameters and treatment effect was determined using multivariable ordinal logistic regression. Interaction with treatment effect was also tested for mismatch (core 1.2; penumbra core >10 mL). The adjusted odds ratio for improved functional outcome for ischemic core, percentage ischemic core, and penumbra were 0.79 per 10 mL (95% confidence interval: 0.71-0.89; P<0.001), 0.82 per 10% (95% confidence interval: 0.66-0.90; P=0.002), and 0.97 per 10 mL (96% confidence interval: 0.92-1.01; P=0.15), respectively. No significant interaction between any of the CTP-derived parameters and treatment effect was observed. We observed no significant interaction between mismatch and treatment effect. CTP seems useful for predicting functional outcome, but cannot reliably identify patients who will not benefit from intra-arterial therapy. © 2015 American Heart Association, Inc.

  16. Low-dose intra-arterial contrast-enhanced MR aortography in patients based on a theoretically derived injection protocol

    Energy Technology Data Exchange (ETDEWEB)

    Potthast, S.; Bongartz, G.M.; Huegli, R.; Bilecen, D. [University Hospital of Basel, Department of Diagnostic Radiology, Basel (Switzerland); Schulte, A.-C. [University of Basel, Biocenter, Basel (Switzerland); Aschwanden, M. [University of Basel, Department of Angiology, Basel (Switzerland)

    2005-11-01

    Multiple intra-arterial contrast agent injections are necessary during MR-guided endovascular interventions. In respect to the approved limits of maximum daily gadolinium dose, a low-dose injection protocol is mandatory. The objective of this study was to derive and apply a low-dose injection protocol for intra-arterial 3D contrast-enhanced MR aortography in patients. Injection rate (Q{sub inj}), concentration of injected gadolinium [Gd]{sub inj} and aortal blood flow rate (Q{sub blood}) were included for the theoretical evaluation of signal intensity (SI) of the arterial lumen. SI simulations were carried out at Q{sub inj}=2 versus 4 ml/s in the [Gd]{sub inj} range between 0-500 mM. Q{sub inj} and [Gd]{sub inj} with SI above the 75% threshold of the maximal SI were regarded as optimal injection parameters. [Gd]{sub inj}=50 mM and Q{sub inj}=4 ml/s were considered as optimal and were administered in five patients for 3D MR aortography. All images revealed clear delineation of the abdominal aorta and its major branches. Mean{+-}SD of contrast-to-noise ratios of the abdominal aorta, common iliac and renal artery were 70.2{+-}15.2, 58.6{+-}12.3 and 67.4{+-}12.3. Approximately seven intra-aortal injections would be permissible in patients during MR-guided interventions without exceeding the maximal dose of gadolinium. (orig.)

  17. Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

    Science.gov (United States)

    Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

    2014-01-01

    Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

  18. Intra-arterial infusion of Solcoseryl: a clinical trial of a method of treatment for pre-gangrene of the lower limb.

    Science.gov (United States)

    Charlesworth, D; Harris, P L; Palmer, M K

    1975-05-01

    A randomized double blind trial of the drug Solcoseryl given by intra-arterial infusion was carried out on 57 patients with pre-gangrene of the lower limb. A sequential analysis was carried out and the trial stopped when the results showed a statistically significant result in favour of the active drug.

  19. Intra-arterial tert-Butyl-hydroperoxide infusion induces an exacerbated sensory response in the rat hind limb and is associated with an impaired tissue oxygen uptake.

    NARCIS (Netherlands)

    Tan, E.C.T.H.; Goor, H. van; Bahrami, S.; Kozlov, A.V.; Leixnering, M.; Redl, H.; Goris, R.J.A.

    2011-01-01

    The objective of this study was to investigate oxidative stress and oxygen extraction mechanisms in an animal model of continuous intra-arterial infusion of a free radical donor and in an in vitro model using isolated mitochondria. tert-Butyl-hydroperoxide (tert-BuOOH, 25 mM) was infused for 24 h in

  20. Superior diagnostic strength of combined contrast enhanced MR-angiography and MR-imaging compared to intra-arterial DSA in liver transplantation candidates

    NARCIS (Netherlands)

    Boeve, WJ; Kok, T; Haagsma, EB; Slooff, MJH; Sluiter, WJ; Kamman, RL

    2001-01-01

    To evaluate the diagnostic value of combined contrast enhanced MRA (ce-MRA) and MRI compared to that of intra-arterial DSA (i.a.DSA) in liver transplantation, transjugular porto-systemic (TIPSS) and spleno-renal shunt candidates. 50 patients in the workup for liver transplantation underwent ce-MRA/M

  1. Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhao Q

    2016-12-01

    Full Text Available Qianqian Zhao,1,2 Kunli Zhu,2 Jinbo Yue,2 Zhonghua Qi,1,2 Shumei Jiang,2 Xiaoqing Xu,2 Rui Feng,2 Renben Wang2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 2Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People’s Republic of China Purpose: Numerous studies have tried to combine transarterial chemoembolization (TACE or hepatic arterial infusion chemotherapy (HAIC with radiotherapy (RT for the treatment of hepatocellular carcinoma (HCC patients with portal vein tumor thrombus (PVTT. However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT.Methods: PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR, overall survival (OS, and adverse events.Results: Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07–5.80; P<0.001 and OS (HR, 0.69; 95% CI, 0.57–0.83; P=0.001, but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67–2.79; P=0.390. The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478–13.56; P<0.001 and thrombocytopenia (OR, 3.77; 95% CI, 1.06–13.43; P=0.041 was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group.Conclusion: Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could

  2. Photochemical Studies on Aqueous Carboplatin

    Institute of Scientific and Technical Information of China (English)

    刘伟平; 杨懿昆; 阙振寰; 熊惠周

    1994-01-01

    The photochemical products,quantum yields and mechanisms of aqueous Carboplatin havebeen studied at 313 and 254 nm irradiation.Excitation in the ligand field bands 1A1→1A2 and 1A1→1E leads tosubstitution reactions,giving diaquodiammineplatinum and tetraaquoplatinum.And then these complexesundergo thermally hydrolysis and polymerization producing polymeric hydroxo-bridged complexes.Oxygen isnot involved in the reactions.Excitation in the charge-transfer band 1A1→1A2u results in redox reaction.Metallic platinum and diaquodiammineplatinum are formed,respectively,in the absence and the presence ofoxygen.

  3. Analysis of the Curative Effect of Preoperative Intra-Arterial Infusion Chemoembolization on Stage,IB2-IIB Uterine Cervix Cancer

    Institute of Scientific and Technical Information of China (English)

    Huashu Li; Fuxiang Liu; Guohe Zhou; Zhaoxia Mo

    2008-01-01

    OBJECTIVE To investigate the short-term and long-term therapeutic efficacy of preoperative intra-arterial infusion chemo-embolization on stage IB2-IIB Uterine cervix cancer (UCC). METHODS A total of 143 patients with Stage IB2-lIB UCC were divided into a clinical trial group and a control group. The patients in the clinical trial group (n/=86) were treated with a combined therapy, i.e. preoperative intra-arterial infusion chemo-embolization, surgical therapy and postoperative radiotherapy, and those in the control group(n=57)were given surgical therapy and post-operative radiotherapy. The adverse effects, changes in local lesion and pathological examinations of the cancer, and the state during the surgery were observed after the intra-arterial infusion chemo-embolization. The survival rate and recurrence rate between the two groups were compared. RESUITS The total effective rate of the intra- arterial infusion chemo-embolization on Stage IB2-IIB UCC was 93.02%. The treatment could reduce tumor size, bring about retro-conversions of the clinical stage of the tumors and pathological grade of the cancer cells, and decrease the quantity, of intra-operative blood loss as well as the operating time. It could significantly improve the 5-year survival rate (P<0.05), and reduce the 2 and 5-yeartumor recurrence rates(P<0.05). Moreover, its side effects were little. CONCLUSIOAN Preoperative intra-arterial infusion chemo-embolization can create conditions for radical operation, lower the postoperative recurrence rate, and improve the prognosis in the patients with UCC. It is an effctive therapy in treating UCC.

  4. Effectiveness of sublingual nitroglycerin before puncture compared with conventional intra-arterial nitroglycerin in transradial procedures: a randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Turan, Burak, E-mail: drburakturan@gmail.com; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

    2015-10-15

    Aim: Sublingual (SL) nitroglycerin administered before radial artery puncture can improve cannulation success and decrease the incidence of radial artery spasm (RAS) compared with intra-arterial (IA) nitroglycerin in transradial procedures. Methods: Patients undergoing diagnostic transradial angiography were randomized to IA (200 mcg) or SL (400 mcg) nitroglycerin. Primary endpoints were puncture time and puncture attempts. Secondary endpoint was the incidence of RAS. Results: Total of 101 participants (mean age 60 ± 11 years, 53% male) were randomized (51 in IA and 50 in SL groups). Puncture time (50 [36–75] vs 50 [35–90] sec), puncture attempts (1.18 ± 0.48 vs 1.20 ± 0.49), multiple punctures (13.7 vs 16.0%) and RAS (19.6 vs 24.0%) were not statistically different between IA vs SL groups respectively. A composite endpoint of all adverse events related to transradial angiography (multiple punctures, RAS, access site crossover, hypotension/bradycardia associated with nitroglycerin and radial artery occlusion) was very similar in IA vs SL groups (39 vs 40%, respectively). However puncture time was significantly longer with SL nitroglycerin in patients < 1.65 m height (47 [36–66] vs 63 [41–110] sec, p = 0.042). Multiple punctures seemed higher with SL nitroglycerin in patients with diabetes (0 vs 30%, p = 0.028) or in patients < 1.65 m height (7.4 vs 25%, p = 0.085). Likewise, RAS with SL nitroglycerin seemed more frequent in smokers compared to IA nitroglycerin (0 vs 27%, p = 0.089). Conclusions: SL nitroglycerin was not different from IA nitroglycerin in terms of efficiency and safety in overall study population. However it may be inferior to IA nitroglycerin in certain subgroups (shorter individuals, diabetics and smokers). - Highlights: • Improvement in radial artery puncture time and success with subcutaneous nitrate was reported. • Giving nitrate sublingually may have vasodilation along entire length of radial artery and may prevent RAS

  5. Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas.

    KAUST Repository

    Jain, Harsh Vardhan

    2014-01-06

    Platinum drug-resistance in ovarian cancers mediated by anti-apoptotic proteins such as Bcl-xL is a major factor contributing to the chemotherapeutic resistance of recurrent disease. Consequently, concurrent inhibition of Bcl-xL in combination with chemotherapy may improve treatment outcomes for patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-xL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo experimental data, wherein xenografts established in mice were treated with ABT-737 and/or carboplatin on a fixed periodic schedule. The validated model is used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the infusion-duration of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin given weekly combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. The potential of combination therapy to prevent or delay the onset of carboplatin-resistance is also investigated. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, drug delivery schedules that induce tumor remission with even low doses of combination therapy can be identified. Intrinsic resistance due to pre-existing cohorts of resistant cells precludes tumor regression, but dosing strategies that extend disease-free survival periods can still be identified. These results highlight the potential of our model to accelerate the development of novel therapeutics such as BH3 mimetics.

  6. Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis

    Science.gov (United States)

    Zhao, Qianqian; Zhu, Kunli; Yue, Jinbo; Qi, Zhonghua; Jiang, Shumei; Xu, Xiaoqing; Feng, Rui; Wang, Renben

    2017-01-01

    Purpose Numerous studies have tried to combine transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) with radiotherapy (RT) for the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT. Methods PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR), overall survival (OS), and adverse events. Results Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07–5.80; P<0.001) and OS (HR, 0.69; 95% CI, 0.57–0.83; P=0.001), but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67–2.79; P=0.390). The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478–13.56; P<0.001) and thrombocytopenia (OR, 3.77; 95% CI, 1.06–13.43; P=0.041) was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group. Conclusion Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could bring higher ORR of PVTT and better survival benefits. This combination therapy was also associated with a significantly increased risk of adverse events. However, they were mostly mild to moderate and successfully treated with conservative treatment. PMID:28053537

  7. Desensitization with oxaliplatin in patients intolerant of carboplatin desensitization.

    Science.gov (United States)

    Rose, Peter G; Metz, Carol; Link, Nicolas

    2014-11-01

    The tolerance and efficacy of oxaliplatin desensitization in patients who were intolerant of carboplatin desensitization were determined. We retrospectively reviewed the Gynecologic Oncology patients who received carboplatin or oxaliplatin from December 2007 until August 2014. The number of treatments and number of patients of carboplatin standard infusions, carboplatin desensitizations, and oxaliplatin desensitizations were determined. Carboplatin infusions (2294) were administered to 281 patients. Twenty-eight (10%) of these patients developed carboplatin hypersensitivity and were treated with 205 carboplatin desensitizations. Nine (29%) patients were subsequently treated with 61 oxaliplatin desensitizations due to intolerance of carboplatin desensitization. Nine of the 10 patients tolerated this infusion well. Four of 9 evaluable patients had an objective response, 2 complete and 2 partial. Oxaliplatin desensitization seems well tolerated and effective in most patients who are intolerant of carboplatin desensitization.

  8. Multimodal assessment of spatial distribution of drug-tracer uptake by brain tissue after intra-arterial injections

    Science.gov (United States)

    Singh-Moon, Rajinder; Chaudhuri, Durba; Wang, Mei; Straubinger, Robert; Bigio, Irving J.; Joshi, Shailendra

    2014-02-01

    It is challenging to track the rapid changes in drug concentrations after intra-arterial (IA) administration to elucidate the pharmacokinetics of this method of drug delivery. Traditional pharmacokinetic parameters (such as protein binding) that are highly relevant to intravenous (IV) administration do not seem to apply to IA injections. Regional drug delivery is affected by the biomechanics of drug injection, resting blood flow, and local tissue extraction. In-vivo and ex-vivo, optical methods for spatial mapping of drug deposition can assist in visualizing drug distributions and aid in the screening of potential drugs and carrier candidates. We present a multimodal approach for the assessment of drug distribution in postmortem tissue specimens using diffuse reflectance spectroscopy, multispectral imaging, and confocal microscopy and demonstrate feasibility of distinguishing route of administration advantages of liposome-dye conjugate delivery. The results of this study suggest that insight on drug dynamics gained by this aggregated approach can be used to help screen and/or optimize potential drug candidates and drug delivery protocols.

  9. Clinical evaluation of intra-arterial infusion chemotherapy for advanced or recurrent cervical cancer with or without radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kaneyasu, Yuko; Kita-Okawa, Midori; Kokubo, Nahoko; Karasawa, Kumiko; Fukuhara, Noboru; Toda, Jo; Okawa, Tomohiko [Tokyo Women`s Medical Coll. (Japan)

    1997-09-01

    We analyzed 52 cases of advanced or recurrent cancer of the cervix treated by intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. IAIC regimen was separated into two groups: Group I consisted of 5-FU + MMC {+-} ADR (30 cases) and Group II of CDDP + MMC {+-} 5-FU (22 cases). The tip of the catheter was placed in the bifurcation of abdominal aorta or the bilateral internal iliac arteries (7 cases). The overall response rate (CR + PR) was 71%, 87% in patients given radiotherapy, 50% in those without radiotherapy, and 100% in primary cases. The five-year survival rate was 20% in primary cases, 14% in recurrent cases, 3% in Group I and 38% in Group II (p=0.00182) by chemotherapy regimen. Severe (more than grade III) hematological acute side effect was 48% for all cases, but recovered by interruption of drugs. In 7 cases in which the tip of the catheter was placed in internal iliac arteries, there were severe skin ulcers in 2 cases and severe pain of leg or gluteal region requiring narcotics in 2 cases. These data suggest that IAIC mainly with cisplatin with or without radiotherapy is one of the effective treatments for advanced or recurrent cervix cancer. But we should check the blood flow distribution periodically, and control the concentration of drugs. (author)

  10. Change apparent diffusion coefficient immediately after recanalization through intra-arterial revascularization therapy in acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Ji Eun; Yeom, Joeng A; Kim, Young Soo; Yoon, Chang Hyo; Park, Min Gyu; Park, Kyung Pil; Baik, Seung Kug [Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2016-04-15

    Intra-arterial revascularization therapy (IART) for acute ischemic stroke has become increasingly popular recently. However, early change in apparent diffusion coefficient (ADC) values after full recanalization in human stroke has not received much attention. The aim of this study was to evaluate ADC changes immediately after interventional full-recanalization in patients with acute ischemic stroke. ADC values of 25 lesions from 18 acute ischemic stroke patients were recorded with both pre- and post-recanalization ADC maps. Measurement was done by placing region of interests over the representative images of the lesion. For analysis, lesions were divided into territorial infarction (TI) and watershed infarction (WI). Mean ADC values of the overall 25 lesions before IART were 415.12 × 10-6 mm{sup 2}/sec, and increased to 619.08 × 10-6 mm{sup 2}/sec after the IART. Average relative ADC (rADC) value for 22 TI increased from 0.59 to 0.92 (p < 0.000), whereas, average rADC value for 3 WI did not change significantly. There was a conspicuous increase of ADC values immediately after full-recanalization in TI lesions. On the other hand, WI lesions did not show significant change in ADC values after recanalization.

  11. Superselective Intra-Arterial Ethanol Sclerotherapy of Feeding Artery and Nidal Aneurysms in Ruptured Cerebral Arteriovenous Malformations.

    Science.gov (United States)

    Settecase, F; Hetts, S W; Nicholson, A D; Amans, M R; Cooke, D L; Dowd, C F; Higashida, R T; Halbach, V V

    2016-04-01

    In the endovascular treatment of cerebral arteriovenous malformations, ethanol sclerotherapy is seldom used due to safety concerns. However, when limited reflux of an embolic agent is permissible or when there is a long distance to the target, ethanol may be preferable. We reviewed 10 patients with 14 cerebral AVM feeding artery aneurysms or intranidal aneurysms treated with intra-arterial ethanol sclerotherapy at our institution between 2005 and 2014. All patients presented with acute intracranial hemorrhage. Thirteen of 14 aneurysms were treated primarily with 60%-80% ethanol into the feeding artery. Complete target feeding artery and aneurysm occlusion was seen in all cases; 8/13 (62%) were occluded by using ethanol alone. No retreatments or recurrences were seen. One permanent neurologic deficit (1/13, 7.7%) and no deaths occurred. In a subset of ruptured cerebral AVMs, ethanol sclerotherapy of feeding artery aneurysms and intranidal aneurysms can be performed with a high degree of technical success and a low rate of complication. © 2016 by American Journal of Neuroradiology.

  12. Predictive Factors of Downstaging of Hepatocellular Carcinoma Beyond the Milan Criteria Treated with Intra-arterial Therapies

    Energy Technology Data Exchange (ETDEWEB)

    Bova, Valentina; Miraglia, Roberto, E-mail: rmiraglia@ismett.edu; Maruzzelli, Luigi [Mediterranean Institute for Transplantation and Advanced Specialized Therapies, (ISMETT), Department of Diagnostic and Interventional Radiology (Italy); Vizzini, Giovanni Battista [Mediterranean Institute for Transplantation and Advanced Specialized Therapies, (ISMETT), Department of Hepatology (Italy); Luca, Angelo [Mediterranean Institute for Transplantation and Advanced Specialized Therapies, (ISMETT), Department of Diagnostic and Interventional Radiology (Italy)

    2013-04-15

    This study was designed to analyze the clinical results in patients suitable for liver transplantation with hepatocellular carcinoma (HCC) who exceeded Milan criteria, which underwent intra-arterial therapies (IAT), to determine predictive factors of successful downstaging. A total of 277 consecutive patients with cirrhosis and HCC were treated by IAT (transarterial oily chemoembolization, transarterial chemoembolization, transarterial embolization) in a single center. Eighty patients exceed the Milan criteria. Patients with infiltrative HCC, hypovascular HCC, and portal vein thrombosis were excluded, with a final study population of 48 patients. Tumor response to IAT was evaluated with CT and/or MRI according to modified RECIST criteria. Successful downstaging was defined as a reduction in the number and size of viable tumors to within the Milan criteria, and serum alpha-fetoprotein (AFP) <100 ng/mL, for at least 6 months. Nineteen patients (39 %) had their tumors successfully downstaged; 29 patients (61 %) did not. Multivariate analysis showed that AFP level <100 ng/mL and 3-year calculated survival probability using the Metroticket calculator were the only independent predictors of successful downstaging (p < 0.023 and p < 0.049 respectively). Biological characteristics of HCC as AFP levels <100 ng/mL and high 3-year calculated survival probability may predict a good response to downstage after IAT.

  13. Intra-arterial therapy for cardio embolic internal carotid artery terminus occlusion: The past and present status in real practice

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Seung Guk; Jung, Cheol Kyu; KIm, Jae Hyoung; Choi, Byung Se; Kim, Beomn Joon; Han, Moon Ku; Bae, Hee Joon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Kwon, Bae Ju [Dept. of Radiology, Myongji Hospital, Goyang (Korea, Republic of); Cha, Sang Hoon [Dept. of Radiology, Chungbuk National University College of Medicine, Daejeon (Korea, Republic of)

    2015-10-15

    There is little data on the effect of intra-arterial therapy (IAT) in acute cardioembolic internal carotid artery terminus (ICAT) occlusion that has poor prognosis. We determined procedural and clinical outcomes in patients with acute cardioembolic ICAT occlusion treated with different methods of IAT. On retrospective review of our registry, patients with cardioembolic ICAT occlusion were categorized as thrombolytic-based IAT group (TLG) and thrombectomy-based IAT group (TEG) according to the primary endovascular technique. Subsequently, procedural and clinical outcomes were compared. Fifty-five patients had cardioembolic ICAT occlusion and 18 patients were assigned to TLG and 37 patients to TEG. The rate of complete reperfusion was significantly higher and the groin puncture to reperfusion time was significantly shorter in TEG than those in TLG. There was a trend towards functional outcome at 3 months in the TEG group; however, it was not statistically significant (p = 0.06). Age, baseline Albert Stroke program early CT score and puncture to reperfusion time were factors affecting unfavorable outcome at 3 months, on multivariable analysis. Thrombectomy-based IAT has advantages over thrombolytic-based IAT in terms of the reduction of groin puncture to reperfusion time and improvement of the rate of complete reperfusion.

  14. Convulsion during intra-arterial infusion of fasudil hydrochloride for the treatment of cerebral vasospasm following subarachnoid hemorrhage.

    Science.gov (United States)

    Enomoto, Yukiko; Yoshimura, Shinichi; Yamada, Kiyofumi; Iwama, Toru

    2010-01-01

    The incidence of convulsion and associated factors were retrospectively analyzed in 23 patients with symptomatic cerebral vasospasm following subarachnoid hemorrhage (SAH) who underwent a total of 31 intra-arterial infusion of fasudil hydrochloride (IAFH) procedures in 49 vessels. Fasudil hydrochloride was administered by superselective infusion via a microcatheter positioned at the proximal portion of the affected artery. Thirteen procedures were performed by manually controlled infusion of 30-75 mg fasudil hydrochloride (1.2-3.75 mg/ml) for approximately 10 minutes. Eighteen procedures were performed by continuous infusion of 60 mg fasudil hydrochloride (1.2 mg/ml) by infusion pump at a constant rate of 3 mg/min. Neurological improvement was observed after 18 of 22 procedures in patients with neurological deterioration due to vasospasm. Convulsion during IAFH developed in 4 patients, all treated by manual infusion (p convulsion during IAFH. IAFH was effective for treating cerebral vasospasm following aneurysmal SAH. IAFH at a constant rate of 3 mg/min delivered by infusion pump improved the symptoms of cerebral vasospasm and prevented convulsions during IAFH.

  15. Image-Based Analysis of Tumor Localization After Intra-Arterial Delivery of Technetium-99m-Labeled SPIO Using SPECT/CT and MRI

    Directory of Open Access Journals (Sweden)

    In Joon Lee MD, PhD

    2017-01-01

    Full Text Available The aim of this study is to evaluate the localization of 99mTc-labeled dextran-coated superparamagnetic iron oxide (SPIO nanoparticles to the liver tumor using image-based analysis. We delivered 99mTc-SPIO intravenously or intra-arterially (IA with/without Lipiodol to compare the tumor localization by gamma scintigraphy, single-photon emission computed tomography (SPECT, and magnetic resonance imaging (MRI in a rabbit liver tumor. The gamma and SPECT image-based analysis shows that the uptake ratio of the tumor to the normal liver parenchyma is highest after delivery of 99mTc-SPIO with Lipiodol IA and that well correlates with the trend of the signal decrease in the liver MRIs. Intra-arterial delivery of SPIO with Lipiodol might be a good drug delivery system targeting the hepatic tumors, as confirmed by image-based analysis.

  16. Intra-Arterially Delivered Mesenchymal Stem Cells Are Not Detected in the Brain Parenchyma in an Alzheimer’s Disease Mouse Model

    Science.gov (United States)

    Lee, Na Kyung; Yang, Jehoon; Chang, Eun Hyuk; Park, Sang Eon; Lee, Jeongmin; Choi, Soo Jin; Oh, Wonil; Chang, Jong Wook; Na, Duk L.

    2016-01-01

    Mesenchymal stem cells (MSCs) have a promising role as a therapeutic agent for neurodegenerative diseases such as Alzheimer’s disease (AD). Prior studies suggested that intra-arterially administered MSCs are engrafted into the brain in stroke or traumatic brain injury (TBI) animal models. However, a controversial standpoint exists in terms of the integrity of the blood brain barrier (BBB) in transgenic AD mice. The primary goal of this study was to explore the feasibility of delivering human umbilical cord-blood derived mesenchymal stem cells (hUCB-MSCs) into the brains of non-transgenic WT (C3H/C57) and transgenic AD (APP/PS1) mice through the intra-arterial (IA) route. Through two experiments, mice were infused with hUCB-MSCs via the right internal carotid artery and were sacrificed at two different time points: 6 hours (experiment 1) or 5 minutes (experiment 2) after infusion. In both experiments, no cells were detected in the brain parenchyma while MSCs were detected in the cerebrovasculature in experiment 2. The results from this study highlight that intra-arterial delivery of MSCs is not the most favorable route to be implemented as a potential therapeutic approach for AD. PMID:27203695

  17. The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs

    Directory of Open Access Journals (Sweden)

    Hongting Jin

    2016-01-01

    Full Text Available This study aimed to investigate if autologous bone marrow mesenchymal stem cells (MSCs could treat osteonecrosis of the femoral head (ONFH and what the fate and distribution of the cells are in dogs. Twelve Beagle dogs were randomly divided into two groups: MSCs group and SHAM operated group. After three weeks, dogs in MSCs group and SHAM operated group were intra-arterially injected with autologous MSCs and 0.9% normal saline, respectively. Eight weeks after treatment, the necrotic volume of the femoral heads was significantly reduced in MSCs group. Moreover, the trabecular bone volume was increased and the empty lacunae rate was decreased in MSCs group. In addition, the BrdU-positive MSCs were unevenly distributed in femoral heads and various vital organs. But no obvious abnormalities were observed. Furthermore, most of BrdU-positive MSCs in necrotic region expressed osteocalcin in MSCs group and a few expressed peroxisome proliferator-activated receptor-γ (PPAR-γ. Taken together, these data indicated that intra-arterially infused MSCs could migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. It suggests that intra-arterial infusion of autologous MSCs might be a feasible and relatively safe method for the treatment of femoral head necrosis.

  18. Influential factors of clinical outcome of local intra-arterial thrombolysis using urokinase in patients with hyperacute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jae Min; Yoon, Woong; Kim, Jae Kyu; Seo, Jeong Jin; Heo, Sook Hee; Park, Jin Gyoon; Jeong, Yoon Yeon; Kang, Heoung Keun [Chonam University Hospital, Kwangju (Korea, Republic of)

    2002-10-01

    To evaluate the clinical outcome and other relevant factors in cases where local intra-arterial thrombolysis (LIT) is used for the treatment of hyperacute ischemic stroke. Forty-eight hyperacute ischemic stroke patients were treated by LIT, using urokinase, within six hours of ictus, and for evaluation of their neurological status, the national institutes of health stroke scale (NIHSS) score was used. Angiography recanalization was classified according to Mori recanalization grades. Three months after LIT, the outcome was assessed by clinical examination using the modified rankin scale (good outcome: RS=0-3; poor outcome: RS=4-6). In all patients, the findings of pre- and post- LIT CT, and angiography, as well as neurological status and hemorrhagic complications, were also analysed. Thirty-three patients had occlusions of the middle cerebral artery (MCA), and 15, of the internal carotid artery (ICA). The NIHSS score averaged 16.9 at the onset of therapy and 13.5 at 24 hours later. Successful recanalization (Mori grade 3,4) was achieved in 28 (58.3%) of 48 patients, but in 20 (41.7%) the attempt failed. Twenty-two (45.8%) of the 48 patients had a good outcome, but in (54.2%) the outcome was poor. Thirteen (40.6%) of 32 patients with MCA occlusions and 13 (81.2%) of 16 with ICA occlusions had a poor outcome. Eight patients (16.7%) died. Overall, hemorrhages occured in 20 (41.7%) of 48 patients, with symptomatic hemorrhage in ten. Five (50%) of these ten died. LIT using urokinase for hyperacute ischemic stroke is feasible; patients with MCA occlusions had better outcomes than those with ICA occlusions. Hemorrhagic complications of LIT were frequent, and in cases of symptomatic hemorrhage a fatal outcome may be expected.

  19. Intra-arterial administration improves temozolomide delivery and efficacy in a model of intracerebral metastasis, but has unexpected brain toxicity.

    Science.gov (United States)

    Muldoon, Leslie L; Pagel, Michael A; Netto, Joao Prola; Neuwelt, Edward A

    2016-02-01

    We tested the hypothesis that intra-arterial (IA) infusion of temozolomide into the internal carotid artery would safely improve drug delivery to brain and enhance chemotherapy efficacy in a chemosensitive rat brain tumor model. Quantitative autoradiography after 25 µCi (14)C-temozolomide was given by oral, intravenous, or IA route of administration, or IA with osmotic blood-brain barrier disruption (BBBD) (n = 5-7 per group) showed that both IA and IA/BBBD administration increased drug delivery in tumor by over threefold compared to normal brain (P Temozolomide (20 mg/kg; ~150 mg/m(2)) increased median survival when given by oral (25.5 days), intravenous (25.5 days), or IA (33 days) route of administration, compared to 17.5 days in untreated controls (n = 8 per group; overall P temozolomide was significantly longer than all other groups (P temozolomide was toxic in the efficacy study, but there was no evidence of symptomatic neurotoxicity in rats given IA temozolomide. After these promising animal results, a 49 year old male with glioblastoma multiforme who failed all standard therapy received temozolomide 100 mg/m(2) IA. Upon initiation of the second course of IA infusion the patient had increased heart rate, blood pressure, and rash, and the procedure was terminated without sequelae. Follow up IA infusion of temozolomide diluent in normal rats showed damaged cerebrovasculature as determined by dye leakage. These results demonstrate that IA infusion of temozolomide was toxic, with or without BBBD. We conclude that under the current formulation temozolomide is not safe for IA infusion in patients.

  20. Continuous non-invasive finger arterial pressure monitoring reflects intra-arterial pressure changes in children undergoing cardiac surgery.

    Science.gov (United States)

    Hofhuizen, C M; Lemson, J; Hemelaar, A E A; Settels, J J; Schraa, O; Singh, S K; van der Hoeven, J G; Scheffer, G J

    2010-10-01

    Continuous non-invasive measurement of finger arterial pressure (FAP) is a reliable technology in adults. FAP is measured with an inflatable cuff around the finger and simultaneously converted to a reconstructed brachial artery pressure waveform (reBAP) by the Nexfin™ device. We assessed the adequacy of a prototype device (Nexfin-paediatric), designed for a paediatric population, for detecting rapid arterial pressure changes in children during cardiac surgery. Thirteen anaesthetized children with a median age of 11 months (2 months-7 yr) undergoing congenital cardiac surgery were included in the study. reBAP and intra-arterial pressure (IAP) were recorded simultaneously during the surgical procedure. To assess the accuracy of reBAP in tracking arterial pressure changes, the four largest IAP variations within a 5 min time interval were identified from each procedure. These variations were compared offline with reBAP during a 10 s control period before and a 10 s period after an arterial pressure change had occurred. In 10 out of 13 children, a non-invasive arterial pressure recording could be obtained. Therefore, recordings from these 10 children were eligible for further analysis, resulting in 40 data points. The correlation coefficient between reBAP and IAP in tracking mean arterial pressure (MAP) changes was 0.98. reBAP followed changes in IAP with a mean bias for systolic, diastolic arterial pressure, and MAP of 0.0 mm Hg (sd 5.8), 0.1 (sd 2.8), and 0.19 (sd 2.7), respectively. The prototype device closely follows arterial pressure changes in children. However, in a considerable number of attempts, obtaining a signal was time-consuming or unsuccessful. This technique seems promising but requires further technical development.

  1. Intra-arterial high signals on arterial spin labeling perfusion images predict the occluded internal carotid artery segment

    Energy Technology Data Exchange (ETDEWEB)

    Sogabe, Shu; Satomi, Junichiro; Tada, Yoshiteru; Kanematsu, Yasuhisa; Kuwayama, Kazuyuki; Yagi, Kenji; Yoshioka, Shotaro; Mizobuchi, Yoshifumi; Mure, Hideo; Yamaguchi, Izumi; Kitazato, Keiko T.; Nagahiro, Shinji [Tokushima University Graduate School, Department of Neurosurgery, Tokushima (Japan); Abe, Takashi; Harada, Masafumi [Tokushima University Graduate School, Department of Radiology, Tokushima (Japan); Yamamoto, Nobuaki; Kaji, Ryuji [Tokushima University Graduate School, Department of Clinical Neurosciences, Institute of Biomedical Biosciences, Tokushima (Japan)

    2017-06-15

    Arterial spin labeling (ASL) involves perfusion imaging using the inverted magnetization of arterial water. If the arterial arrival times are longer than the post-labeling delay, labeled spins are visible on ASL images as bright, high intra-arterial signals (IASs); such signals were found within occluded vessels of patients with acute ischemic stroke. The identification of the occluded segment in the internal carotid artery (ICA) is crucial for endovascular treatment. We tested our hypothesis that high IASs on ASL images can predict the occluded segment. Our study included 13 patients with acute ICA occlusion who had undergone angiographic and ASL studies within 48 h of onset. We retrospectively identified the high IAS on ASL images and angiograms and recorded the occluded segment and the number of high IAS-positive slices on ASL images. The ICA segments were classified as cervical (C1), petrous (C2), cavernous (C3), and supraclinoid (C4). Of seven patients with intracranial ICA occlusion, five demonstrated high IASs at C1-C2, suggesting that high IASs could identify stagnant flow proximal to the occluded segment. Among six patients with extracranial ICA occlusion, five presented with high IASs at C3-C4, suggesting that signals could identify the collateral flow via the ophthalmic artery. None had high IASs at C1-C2. The mean number of high IAS-positive slices was significantly higher in patients with intra- than extracranial ICA occlusion. High IASs on ASL images can identify slow stagnant and collateral flow through the ophthalmic artery in patients with acute ICA occlusion and help to predict the occlusion site. (orig.)

  2. Intra-Arterial MR Perfusion Imaging of Meningiomas: Comparison to Digital Subtraction Angiography and Intravenous MR Perfusion Imaging

    Science.gov (United States)

    Martin, Alastair J.; Alexander, Matthew D.; McCoy, David B.; Cooke, Daniel L.; Lillaney, Prasheel; Moftakhar, Parham; Amans, Matthew R.; Settecase, Fabio; Nicholson, Andrew; Dowd, Christopher F.; Halbach, Van V.; Higashida, Randall T.; McDermott, Michael W.; Saloner, David; Hetts, Steven W.

    2016-01-01

    Background and Purpose To evaluate the ability of IA MR perfusion to characterize meningioma blood supply. Methods Studies were performed in a suite comprised of an x-ray angiography unit and 1.5T MR scanner that permitted intraprocedural patient movement between the imaging modalities. Patients underwent intra-arterial (IA) and intravenous (IV) T2* dynamic susceptibility MR perfusion immediately prior to meningioma embolization. Regional tumor arterial supply was characterized by digital subtraction angiography and classified as external carotid artery (ECA) dural, internal carotid artery (ICA) dural, or pial. MR perfusion data regions of interest (ROIs) were analyzed in regions with different vascular supply to extract peak height, full-width at half-maximum (FWHM), relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and mean transit time (MTT). Linear mixed modeling was used to identify perfusion curve parameter differences for each ROI for IA and IV MR imaging techniques. IA vs. IV perfusion parameters were also directly compared for each ROI using linear mixed modeling. Results 18 ROIs were analyzed in 12 patients. Arterial supply was identified as ECA dural (n = 11), ICA dural (n = 4), or pial (n = 3). FWHM, rCBV, and rCBF showed statistically significant differences between ROIs for IA MR perfusion. Peak Height and FWHM showed statistically significant differences between ROIs for IV MR perfusion. RCBV and MTT were significantly lower for IA perfusion in the Dural ECA compared to IV perfusion. Relative CBF in IA MR was found to be significantly higher in the Dural ICA region and MTT significantly lower compared to IV perfusion. PMID:27802268

  3. Intra-Arterial Transplantation of Allogeneic Mesenchymal Stem Cells Mounts Neuroprotective Effects in a Transient Ischemic Stroke Model in Rats: Analyses of Therapeutic Time Window and Its Mechanisms.

    Science.gov (United States)

    Toyoshima, Atsuhiko; Yasuhara, Takao; Kameda, Masahiro; Morimoto, Jun; Takeuchi, Hayato; Wang, Feifei; Sasaki, Tatsuya; Sasada, Susumu; Shinko, Aiko; Wakamori, Takaaki; Okazaki, Mihoko; Kondo, Akihiko; Agari, Takashi; Borlongan, Cesario V; Date, Isao

    2015-01-01

    Intra-arterial stem cell transplantation exerts neuroprotective effects for ischemic stroke. However, the optimal therapeutic time window and mechanisms have not been completely understood. In this study, we investigated the relationship between the timing of intra-arterial transplantation of allogeneic mesenchymal stem cells (MSCs) in ischemic stroke model in rats and its efficacy in acute phase. Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. MSCs (1 × 10(6) cells/ 1 ml PBS) were intra-arterially injected at either 1, 6, 24, or 48 hours (1, 6, 24, 48 h group) after MCAO. PBS (1 ml) was intra-arterially injected to control rats at 1 hour after MCAO. Behavioral test was performed immediately after reperfusion, and at 3, 7 days after MCAO using the Modified Neurological Severity Score (mNSS). Rats were euthanized at 7 days after MCAO for evaluation of infarct volumes and the migration of MSCs. In order to explore potential mechanisms of action, the upregulation of neurotrophic factor and chemotactic cytokine (bFGF, SDF-1α) induced by cell transplantation was examined in another cohort of rats that received intra-arterial transplantation at 24 hours after recanalization then euthanized at 7 days after MCAO for protein assays. Behavioral test at 3 and 7 days after transplantation revealed that stroke rats in 24h group displayed the most robust significant improvements in mNSS compared to stroke rats in all other groups (p'sstroke rats in 24h group were much significantly decreased compared to those in all other groups (p'sstroke functional recovery and reduction of infarct volumes in ischemic stroke model of rats. The upregulation of bFGF and SDF-1α likely played a key mechanistic role in enabling MSC to afford functional effects in stroke. MSC transplantation at 24 hours after recanalization appears to be the optimal timing for ischemic stroke model, which should guide the design of clinical

  4. Definitive radiochemotherapy of advanced head and neck cancer with carboplatin and paclitaxel. A phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Semrau, Robert; Temming, Susanne; Mueller, Rolf-Peter [Cologne Univ., Koeln (Germany). Dept. of Radiation Oncology; Preuss, Simon Florian [Cologne Univ., Koeln (Germany). Dept. of Otorhinolaryngology, Head and Neck Surgery; Klussmann, Jens Peter [Giessen Univ. (Germany). Dept. of Otorhinolaryngology and Head and Neck Surgery; Guntinas-Lichius, Orlando [Friedrich-Schiller Univ. Jena (Germany). Dept. of Otorhinolaryngology and Head and Neck Surgery

    2011-10-15

    To report outcome and toxicity of concurrent radiochemotherapy with carboplatin and paclitaxel in advanced squamous cell carcinomas of the oropharynx and hypopharynx. Advanced inoperable carcinomas of the oropharynx and hypopharynx were treated with either hyper-fractionated, accelerated radiotherapy (50.0 Gy/2.0 with concomitant boost to 69.2 Gy/1.6) or conventional fractionated radiotherapy (70.2-72 Gy/1.8) concurrent with paclitaxel 40 mg/m{sup 2} and carboplatin AUC 1 weekly for 6 weeks. Acute and long-term toxicity was measured according to WHO- and CTC-criteria. A total of 84 patients were included between 2000 and 2008. Median follow-up time of patients alive was 36 months. Conventionally fractionated radiotherapy was given to 16 patients, while 68 patients were treated with concomitant boost. Finally, 88.1% of patients received full dose paclitaxel. Acute mucositis {>=} grade 3 was present in 51.2% of patients, while 6% of patients experienced {>=} grade 3 leucopenia and thrombopenia. A supportive gastric feeding tube was implanted in 89.1% of patients. Overall survival after 2 years was 46.3%, progression-free survival after 2 years was 41.0%. There was no significant survival difference between the different radiotherapy protocols. Concomitant carboplatin and paclitaxel is feasible and effective in advanced carcinomas of the head and neck.

  5. Intra-arterial hepatic chemotherapy for unresectable colorectal liver metastases: a review of medical devices complications in 3172 patients

    Directory of Open Access Journals (Sweden)

    Stefano Bacchetti

    2009-03-01

    .Conclusions: The fully implantable pump, maintaining a continuous infusion through the system, allows the lowest risk for thrombosis and infection and the best median number of cycles of loco-regional chemotherapy in HAI.Keywords: liver metastases, colorectal cancer, medical devices, loco-regional treatments, intra-arterial hepatic chemotherapy

  6. Efficacy and dose-dependent safety of intra-arterial delivery of mesenchymal stem cells in a rodent stroke model.

    Directory of Open Access Journals (Sweden)

    Dileep R Yavagal

    Full Text Available Intra-arterial (IA delivery of mesenchymal stem cells (MSCs for acute ischemic stroke is attractive for clinical translation. However, studies using rat model of stroke have demonstrated that IA MSCs delivery can decrease middle cerebral artery (MCA flow, which may limit its clinical translation. The goal of this study is to identify a dose of IA MSCs (maximum tolerated dose; MTD that does not compromise MCA flow and evaluate its efficacy and optimal timing in a rat model of reversible middle cerebral artery occlusion (rMCAo. We sought to determine if there is a difference in efficacy of acute (1 h versus sub-acute (24 h IA MSCs treatment after rMCAo. Adult female Sprague-Dawley rats underwent rMCAo (90 min and an hour later a single dose of MSCs (at de-escalating doses 1 × 10(6, 5 × 10(5, 2 × 10(5, 1 × 10(5 and 5 × 10(4 was given using IA route. MSCs were suspended in phosphate buffered saline (PBS and PBS alone was used for control experiments. We measured the percent change in mean laser Doppler flow signal over the ipsilateral MCA in de-escalating doses groups to determine MTD. The results demonstrated that the lowering of IA MSC dose to 1 × 10(5 and below did not compromise MCA flow and hence an IA MSC dose of 1 × 10(5 considered as MTD. Subsequently, 1 h and 24 h after rMCAo, rats were treated with IA MSCs or PBS. The 24 h delivery of IA MSCs significantly improved neurodeficit score and reduced the mean infarct volume at one month as compared to control, but not the 1 h delivery. Overall, this study suggests that the IA delivery of MSCs can be performed safely and efficaciously at the MTD of 1 × 10(5 delivered at 24 hours in rodent model of stroke.

  7. Effect of multiple-phase regional intra-arterial infusion chemotherapy on patients with resectable pancreatic head adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    JIN Chen; YAO Lie; LONG Jiang; FU De-liang; YU Xian-jun; XU Jin; YANG Feng; NI Quan-xing

    2009-01-01

    Background Regional intra-arterial infusion chemotherapy (RIAC) has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC (preoperative combined with postoperative RIAC) for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed.Methods Patients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A (n=50) were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B (n=50) were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response (CBR), surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method.Results The pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months

  8. Targeted Intra-arterial Transplantation of Stem Cells to the Injured CNS is More Effective than Intravenous Administration - Engraftment is Dependent on Cell Type and Adhesion Molecule Expression

    DEFF Research Database (Denmark)

    Lundberg, Johan; Södersten, Erik; Sundström, Erik

    2011-01-01

    Stem cell transplantation procedures using intraparenchymal injections cause tissue injury in addition to associated surgical risks. Intra-venous cell administration give engraftment in parenchymal lesions although the method has low efficacy and specificity. In pathological conditions...... with inflammation, such as traumatic brain injury, there is a transient up-regulation of ICAM-1 and VCAM-1 which might provide enviromental cues for migration of stem cells from blood to parenchyma. The aim of this study was to i) analyze the effect of intra-arterial administration on cellular engraftment, ii......) compare engraftment and side effects between three different stem cell systems and iii) analyze gene expression in these three systems....

  9. Intra-Arterial Treatment in Patients with Acute Massive Gastrointestinal Bleeding after Endoscopic Failure: Comparisons between Positive versus Negative Contrast Extravasation Groups

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Wei Chou; Liu, Chang Hsien; Hsu, Hsian He; Huang, Guo Shu; Hsieh, Tasi Yuan; Tsai, Shin Hung; Hsieh, Chung Bao; Yu, Chin Yung [Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (China); Tung, Ho Jui [Asia University, Taichung, Taiwan (CN)

    2011-10-15

    To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemo stasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage.

  10. The relationship between interventionists' experience and clinical and radiological outcome in intra-arterial treatment for acute ischemic stroke. A MR CLEAN pretrial survey.

    Science.gov (United States)

    Beumer, Debbie; van Boxtel, Tiemen H; Schipperen, Stefanie; van Zwam, Wim H; Lycklama À Nijeholt, Geert J; Brouwer, Patrick A; Jenniskens, Sjoerd F M; Schonewille, Wouter J; Vos, Jan Albert; van der Lugt, Aad; Roos, Yvo B; Majoie, Charles B; van Oostenbrugge, Robert J; Dippel, Diederik W J

    2017-06-15

    Intra-arterial treatment in acute ischemic stroke is safe and effective as recently shown in several randomized clinical trials. The level of experience of the interventionist performing the IAT procedure has not been studied. The present study investigates effects of interventionists' experience on technical aspects of the procedure and clinical outcome of the patient. In this study of 313 patients with a proximal intracranial arterial anterior circulation occlusion, treated in the Netherlands from 2002 until participation in the Multicenter Randomized Clinical trial of Endovascular treatment for acute ischemic stroke (MR CLEAN), data were collected retrospectively. The association of the senior interventionists' experience with duration of the procedure, adverse events, recanalization, neurological outcome, and functional outcome at discharge was analyzed. Multiple regression models adjusted for age, sex, stroke severity, carotid terminus occlusion, use of a retrievable stent and onset to door time were used. No association between interventionists' experience and recanalization, neurological outcome, or functional outcome was observed in a strict selection of patients. This strict selection include a start of intra-arterial treatment within 6h, no coagulation disturbances, systolic blood pressureexperience and either serious neurologic adverse events or poor outcomes was observed in this study of treatments by interventionists with experience of experience with procedure times, results and patient outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Dose adjustment of carboplatin in patients on peritoneal dialysis.

    Science.gov (United States)

    Guddati, Achuta K; Joy, Parijat S; Marak, Creticus P

    2014-05-01

    The Calvert equation has been extensively used to determine the dosage of carboplatin. However, in patients on dialysis, it predicts the same dosage regardless of the frequency of dialysis. Clearance of carboplatin during hemodialysis has been studied to a lesser extent, but there have been very few studies which have investigated the clearance of carboplatin in patients on peritoneal dialysis. A mathematical formula is proposed here to predict the dose of carboplatin for a given AUC in patients on peritoneal dialysis. This formula takes into account the frequency of dialysis sessions and the time delay between carboplatin infusion and the initiation of dialysis. The formula predicts an approximately similar dosage of carboplatin as that of the Calvert formula in patients undergoing peritoneal dialysis four times per day if dialysis is initiated 12 h after infusion. The formula may help in guiding the adjustment of carboplatin dose in patients who receive a lesser number of dialysis sessions per day and in those patients whose dialysis is initiated at different times (0-24 h) after carboplatin infusion. It is suggested that usage of this formula will result in a better dosage of carboplatin to suit specific dialysis frequencies in specific patients and eventually may result in a better efficacy and toxicity profile.

  12. Anesthetic strategy during endovascular therapy: General anesthesia or conscious sedation? (GOLIATH - General or Local Anesthesia in Intra Arterial Therapy) A single-center randomized trial

    DEFF Research Database (Denmark)

    Simonsen, Claus Z; Sørensen, Leif H; Juul, Niels

    2016-01-01

    RATIONALE: Endovascular therapy after acute ischemic stroke due to large vessel occlusion is now standard of care. There is equipoise as to what kind of anesthesia patients should receive during the procedure. Observational studies suggest that general anesthesia is associated with worse outcomes...... compared to conscious sedation. However, the findings may have been biased. Randomized clinical trials are needed to determine whether the choice of anesthesia may influence outcome. AIM AND HYPOTHESIS: The objective of GOLIATH (General or Local Anestesia in Intra Arterial Therapy) is to examine whether....... Patients with acute ischemic stroke, scheduled for endovascular therapy, are randomized to receive either general anesthesia or conscious sedation. STUDY OUTCOMES: The primary outcome measure is infarct growth after 48-72 h (determined by serial diffusion-weighted magnetic resonance imaging). Secondary...

  13. Panitumumab-associated encephalopathy after accidental intra-arterial application through dislocated Port-a-Cath device in the left ventricle

    Directory of Open Access Journals (Sweden)

    Slaven Pikija

    2016-11-01

    Full Text Available Acute central nervous system (CNS toxicity and immune-related side effects are increasingly recognized with the use of monoclonal antibodies for cancer therapy. Here, we report a patient who developed of acute-onset encephalopathy and coma, which began shortly after administration of panitumumab for the treatment of metastatic colorectal cancer. Echocardiography revealed that the drug had been infused into the left cardiac ventricle via a dislocated central venous line. Diffusion-weighted magnetic resonance imaging disclosed multiple cortical hyperintensities, which were preferentially located in the frontal lobes. While the neurological condition improved within a few days, the patient died four weeks later. It seems likely that the administration of the antibody via the intra-arterial route contributed to the development of this condition. Toxic encephalopathy may be a hitherto unrecognized complication of panitumumab treatment and should be taken into consideration in patients developing CNS symptoms undergoing this therapy.

  14. The Effect of Short-term Intra-arterial Delivery of Paclitaxel on Neointimal Hyperplasia and the Local Thrombotic Environment after Angioplasty

    Energy Technology Data Exchange (ETDEWEB)

    Yajun, E, E-mail: eyj7681@yahoo.com.cn [Affiliated Hospital of Hebei University, Department of Interventional Radiology (China); He Nengshu, E-mail: eyajun@hotmail.com; Fan Hailun, E-mail: mydream510@yahoo.com.cn [Tianjin Institute of Radiology, General Hospital of Tianjin Medical University, Department of Radiology (China)

    2013-08-01

    PurposeTo evaluate the effects of short-term intra-arterial delivery of paclitaxel on neointimal hyperplasia and the local thrombotic environment after angioplasty.MethodsAn experimental common carotid artery injury model was established in 60 rats, which were divided into experimental groups (40 rats) and controls (20 rats). Local intra-arterial administration of paclitaxel was applied at 2 doses (90 and 180 {mu}g/30 {mu}l), and the effects of short-term delivery of paclitaxel on neointimal hyperplasia and the expression of tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated at days 15 and 30 by hematoxylin and eosin staining and immunohistochemistry.ResultsAt 15 and 30 days after injury, neointimal thickness and area, the ratio of intimal area to medial area and the stenotic rate were all significantly decreased in the group provided the high concentrations (180 {mu}g/30 {mu}l) of paclitaxel for 2 min or 10 min and in the group provided the low concentration (90 {mu}g/30 {mu}l) of paclitaxel for 10 min (p < 0.05). At 30 days after injury, there were no significant changes in TF expression among all experimental groups. PAI-1 expression increased in the neointima of the high concentration 10 min group (p < 0.05), while t-PA expression decreased in the neointima of the high concentration 2 min group (p < 0.05).ConclusionIn the rat common carotid artery injury model, the short-term delivery of paclitaxel could effectively inhibit neointimal hyperplasia in the long term, with very little influence on the local expression of TF and PAI-1.

  15. Case-Control Study of Intra-arterial Verapamil for Intraprostatic Anastomoses to Extraprostatic Arteries in Prostatic Artery Embolization for Benign Prostatic Hypertrophy.

    Science.gov (United States)

    Yu, Simon Chun Ho; Cho, Carmen; Hung, Esther; Wang, Defeng; Chiu, Peter; Yee, Chi Hang; Ng, Anthony

    2017-08-01

    It is hypothesized that intra-arterial administration of verapamil is a safe and effective way to reverse the flow in intraprostatic anastomoses to extraprostatic arteries without compromising treatment outcomes in prostatic artery embolization (PAE) for benign prostatic hypertrophy (BPH). A prospective study of 62 prostate sides in 31 consecutive patients (median age, 66 y; range, 60-71 y) with symptomatic BPH was undertaken. Median prostate volume was 72.4 mL (range, 48.8-85.8 mL), median International Prostate Symptom Score was 21 (range, 15-23), and median urine peak flow rate was 4 mL/s (range, 2-6 mL/s). The arterial anastomoses were classified as types I-III according to vascular morphology. Treatment safety was assessed in terms of adverse events and complications, and treatment effectiveness was assessed in terms of success rate of angiographic flow reversal. The PAE procedure was successfully completed in all 31 patients (100%). Adverse events in both groups were transient and mild and did not necessitate prolonged hospitalization. There was no clinical evidence of any significant nontarget ischemic complication in either group. Intraprostatic anastomosis was diagnosed in 19 of 31 patients (61.3%) and 22 of 62 prostate sides (35.5%). Success rates of verapamil treatment were 88.9% overall (20 of 22) and 100% (19 of 19) in type II and III anastomoses. There was no difference between the treatment group and the control group in clinical, urologic, and imaging outcomes of PAE. Intra-arterial verapamil treatment was probably safe and effective in causing flow reversal in type II and III intraprostatic anastomoses and in preventing ischemic complications in PAE for BPH without compromising PAE outcomes. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  16. Antitumor effect of intra-arterial tumor necrosis factor-{alpha} in rats with transplanted intracerebral glioma and its evaluation by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Kunyu; Yoshida, Jun; Wakabayashi, Toshihiko; Sugita, Kenichiro [Nagoya Univ. (Japan). School of Medicine; Kurisu, Kaoru; Uozumi, Tohru; Zieroth, B.F.; Takahashi, Masaya; Yamanaka, Tsuyoshi

    1995-12-01

    Recombinant human TNF-{alpha} was administrated intra-arterially to rats with transplanted intracerebral glioma. 1 x 10{sup 6} of T9 rat glioma cells were transplanted into Fisher 344 rat brain stereotaxically and 1000 units of TNF-{alpha} was administrated at a rate of 100{mu}l/min via an internal carotid artery 1 or 3 weeks after the transplantation. The effects of TNF-{alpha} were evaluated by MRI and histopathological examinations. Neurological symptoms, i.e. hemiparesis, appeared after 9.0{+-}0.63 days and all rats died of tumor overloading 14.5{+-}0.84 days after the transplantation. Single injection of TNF-{alpha} on 7th day after the transplantation induced regression of the tumor size in one of six rats. The tumors were detected 3 days after transplantation by MRI and they were revealed as low/iso intensity mass in T1WI, iso/high intensity in T2WI, and were enhanced by Gd-DTPA heterogenously. On 7/14 days after the transplantation, the tumor grew approximately 7/10 mm in diameter. The single 1000 units of TNF-{alpha} were administrated via an internal carotid artery. Three days after the administration or TNF-{alpha}, regression of the tumor size was seen in one of six rats and decrease of peritumoral edema was seen in three. These effects of TNF-{alpha} were, however, transient and they were not demonstrated on day 7. Single injection of TNF-{alpha} was not effective for large tumors more than 10 mm in diameter seen 14 days after the transplantation. These data suggest that intra-arterial TNF-{alpha} should be administrated at an early stage of the tumor growth and several injections are needed to cause regression in the size of the gliomas. (author).

  17. Intra-arterial thrombolysis using rt-PA in patients with acute stroke due to vessel occlusion of anterior and/or posterior cerebral circulation

    Energy Technology Data Exchange (ETDEWEB)

    Tountopoulou, Argyro; Ahl, Bjoern; Weissenborn, Karin [Hannover Medical School, Department of Neurology and Clinical Neurophysiology, Hannover (Germany); Becker, Hartmut; Goetz, Friedrich [Hannover Medical School, Department of Neuroradiology, Hannover (Germany)

    2008-01-15

    The aim of our study was to evaluate the safety and efficacy of intra-arterial (IA) thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute stroke due to occlusion in the anterior or posterior circulation. We retrospectively analyzed the clinical and radiological data of 88 consecutive patients with acute ischemic stroke who underwent emergency cerebral angiography for the purpose of subsequent IA thrombolysis. The neurological deficit on admission and discharge was graded using the National Institutes of Health Stroke Scale (NIHSS) score. Baseline computer tomography (CT) scans were examined for any signs indicative of cerebral ischemia. The angiographic findings were classified according to the Thrombolysis in Myocardial Infarction (TIMI) score for myocardial infarction. Follow-up CT scans were examined for hemorrhagic complication. Of the 88 patients who underwent IA thrombolysis, 63 presented with complete or partial arterial occlusion in the suspected perfusion area. In these 63 patients, the median NIHSS score dropped from 15 points on admission to 10 points at discharge. The recanalization rate was 52.6% for partial and complete reperfusion. In-hospital mortality was 20.6% (9.1% for carotid, 44.4% for basilar territory occlusion). Intracerebral bleeding (ICB) occurred in 38.6% of the patients with occlusion in the anterior circulation, resulting in these patients presenting a worse clinical outcome than those without ICB. Only minor extracranial bleedings occurred in 20.6% of patients. Patients with ICB had a significantly higher frequency of ischemic signs on the baseline CT scan. Occlusion of a cerebral artery is present in about 75% of the patients eligible for thrombolytic therapy. Intra-arterial thrombolysis using rt-PA in patients with acute ischemic stroke can achieve re-vascularization, although ICB remains the major risk factor affecting its efficacy. (orig.)

  18. Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

    DEFF Research Database (Denmark)

    Helbekkmo, N; Sundstrøm, S H; Aasebø, U;

    2007-01-01

    This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB/IV and ...

  19. Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I131 KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Bosonnet Lorraine

    2009-02-01

    Full Text Available Abstract Background Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I131 in pancreatic cancer (ISRCTN 16857581. Methods Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route. The dose limiting toxicities within each group were determined. Patients were assessed for safety and efficacy and followed up until death. Results Between February 2003 and July 2005, 25 patients were enrolled. Nineteen patients were randomised, 9 to the intravenous and 10 to the intra-arterial arms. In the intra-arterial arm, dose limiting toxicity was seen in 2/6 (33% patients at 50 mCi whereas in the intravenous arm, dose limiting toxicity was noted in 1/6 patients at 50 mCi, but did not occur at 75 mCi (0/3. The overall response rate was 6% (1/18. Median overall survival was 5.2 months (95% confidence interval = 3.3 to 9 months, with no significant difference between the intravenous and intra-arterial arms (log rank test p = 0.79. One patient was still alive at the time of this analysis. Conclusion Dose limiting toxicity for KAb201 with I131 by the intra-arterial route was 50 mCi, while dose limiting toxicity was not reached in the intravenous arm.

  20. FAU regulates carboplatin resistance in ovarian cancer.

    Science.gov (United States)

    Moss, Esther L; Mourtada-Maarabouni, Mirna; Pickard, Mark R; Redman, Charles W; Williams, Gwyn T

    2010-01-01

    The development of chemotherapy resistance by cancer cells is complex, using different mechanisms and pathways. The gene FAU (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene) was identified through functional expression cloning and previous data have shown that overexpression enhances apoptosis in several cell types. We demonstrate that the expression of FAU was reduced in the A2780cis (cisplatin resistant subclone of A2780) cell line compared with the A2780 ovarian cancer cell line, and was directly related to the cell line's sensitivity to carboplatin. Downregulation of FAU in the A2780 cell line by transfection with two predesigned short-interfering RNAs (siRNAs) to FAU resulted in a significant increase in resistance to carboplatin-induced cell death. Downregulation resulted in increased cell viability and reduced apoptosis after 72 hr of drug treatment compared with the negative controls (Kruskal-Wallis P = 0.0002). Transfection of the A2780cis cell line with the pcDNA3 plasmid containing FAU was associated with increased sensitivity to carboplatin-induced apoptosis, with decreased cell viability and increased apoptosis (Mann Whitney P FAU was examined by quantitative real-time reverse transcriptase polymerase chain reaction in normal and malignant ovarian tissue. A significant reduction in the expression of FAU was seen in the malignant compared with normal ovarian samples (Kruskal-Wallis P = 0.0261). These data support a role for FAU in the regulation of platinum-resistance in ovarian cancer. Further research is needed into the apoptotic pathway containing FAU to investigate the potential for targeted therapies to increase or restore the platinum sensitivity of ovarian cancer.

  1. INTRA-ARTERIAL INFUSIONS AND DOPLEROGRAPIC CONTROL FOR COMPLEX TREATMENT OF UPPER AND MIDDLE FACIAL ZONES, CONCOMITANT WITH TRAUMATIC CRANIOCEREBRAL INJURIES.

    Science.gov (United States)

    Lagvilava, G; Gvenetadze, Z; Gibradze, E; Danelia, T; Gvenetadze, G

    2016-02-01

    Maxillofacial traumatic injuries concomitant with craniocerebral trauma are still considered as an actual problem in emergency medicine. For this category of patients one of the dangerous and severe complications is development of inflammatory process in the injured areas. Fracture lines of upper and middle facial zones pass through the accessory sinuses of the nose, maxillary/upper dental arch area and are considered to be open and infected fractures. Combination of these fractures with craniocerebral injuries and especially, with open traumas creates predisposition for development of inflammatory processes in CNS that can result in heavy outcome. 29 patients (among them 5-females and 24 -males) with severe and open craniofacial fractures were observed by the authors. For prevention of inflammatory complications in complex treatment of the patients, intra-arterial infusions of therapeutic agents (wide spectrum of antibiotics, Heparin) were used for stimulation of reparative regeneration in fractured fragments of facial bones. After the main surgical interventions (neurosurgery, surgery of facial bones) sanitation of infected centers (accessory sinuses of the nose, oral cavity) and catheterization of external carotid arteries through the temporal arteries were performed. According to the severity of the trauma and its preferential localization, catheterization of carotid arteries was conducted unilaterally (12 cases) or bilaterally (17 cases). Insertion depth through femoral artery was 6-8 cm. Catheter was stayed in the artery for 7-8 days. Intra-arterial infusions were carried out in the morning and evening. Therapeutic agents for arterial infusion included: antibiotic (Rocephin and its analogues), Heparin. To determine the effectiveness of vascular therapy dopplerography of external carotid artery, its branches and supratrochlear artery was performed. Dopplerography of supratrochlear artery, which is the branch of internal carotid artery, was conducted to detect

  2. The agreement between oscillometric and intra-arterial technique for blood pressure monitoring in the lower extremities for infants and toddlers undergoing aortic coarctation repair.

    Science.gov (United States)

    Peng, Zhe-Zhe; Zhang, Ma-Zhong; Sun, Ying; Bai, Jie; Gu, Hong-Bin; Liu, Pei-Pei; Li, Min; Cai, Mei-Hua

    2016-11-01

    Anesthetic management for patients undergoing surgical repair of aortic coarctation (CoA) should include constant blood pressure monitoring of the right upper extremity and a lower extremity. The delayed or absent pulse in the lower limbs often leads to unsuccessful arterial cannulation in infants and the oscillometric technique used for blood pressure measurement. The aim of this study was to evaluate the agreement between the oscillometric method and intra-arterial technique for blood pressure monitoring in the lower limbs of infants undergoing CoA. A total of 45 infants diagnosed with isolated CoA were initially enrolled in this study and five were excluded because of cannulation failure. Thus, 40 patients had their blood pressure measured simultaneously by both oscillometric technique on the thigh and femoral artery catheterization. After induction and intubation, five pairs of blood pressure readings from each patient were collected in an interval of 3 min. Statistical analysis was accomplished by revised Bland-Altman analysis. There was a strong correlation between oscillometric and invasive blood pressure measurements [systolic blood pressure (SBP) r = 0.771, diastolic blood pressure (DBP) r = 0.704 and mean artery pressure (MAP) r = 0.850]. The mean difference and 95% limits of agreement (95% LOA) between oscillometric and femoral artery blood pressure readings was 3.830 mmHg (-19.297, 26.957) for SBP, -8.725 mmHg (-26.236, 8.786) for DBP, and -3.235 mmHg (-18.842, 12.372) for MAP. There were only one pair of MAP (1/40) and two pairs of SBP readings (2/40) out of range (95% LOA), and all of paired DBP readings were within 95% LOA. There was a good agreement between oscillometric and invasive blood pressure measurements of lower extremities in infants with isolated CoA statistically. However, the oscillometry-measured SBP showed a tendency to overestimate the intra-arterial blood pressure reference, while oscillometry-measured DBP underestimated its

  3. Anesthetic strategy during endovascular therapy: General anesthesia or conscious sedation? (GOLIATH - General or Local Anesthesia in Intra Arterial Therapy) A single-center randomized trial.

    Science.gov (United States)

    Simonsen, Claus Z; Sørensen, Leif H; Juul, Niels; Johnsen, Søren P; Yoo, Albert J; Andersen, Grethe; Rasmussen, Mads

    2016-12-01

    Endovascular therapy after acute ischemic stroke due to large vessel occlusion is now standard of care. There is equipoise as to what kind of anesthesia patients should receive during the procedure. Observational studies suggest that general anesthesia is associated with worse outcomes compared to conscious sedation. However, the findings may have been biased. Randomized clinical trials are needed to determine whether the choice of anesthesia may influence outcome. The objective of GOLIATH (General or Local Anestesia in Intra Arterial Therapy) is to examine whether the choice of anesthetic regime during endovascular therapy for acute ischemic stroke influence patient outcome. Our hypothesis is that that conscious sedation is associated with less infarct growth and better functional outcome. GOLIATH is an investigator-initiated, single-center, randomized study. Patients with acute ischemic stroke, scheduled for endovascular therapy, are randomized to receive either general anesthesia or conscious sedation. The primary outcome measure is infarct growth after 48-72 h (determined by serial diffusion-weighted magnetic resonance imaging). Secondary outcomes include 90-day modified Rankin Scale score, time parameters, blood pressure variables, use of vasopressors, procedural and anesthetic complications, success of revascularization, radiation dose, and amount of contrast media. Choice of anesthesia may influence outcome in acute ischemic stroke patients undergoing endovascular therapy. The results from this study may guide future decisions regarding the optimal anesthetic regime for endovascular therapy. In addition, this study may provide preliminary data for a multicenter randomized trial. © 2016 World Stroke Organization.

  4. Methylene blue intra-arterial staining of resected colorectal cancer specimens improves accuracy of nodal staging: A randomized controlled trial.

    Science.gov (United States)

    Reima, H; Saar, H; Innos, K; Soplepmann, J

    2016-11-01

    Metastatic involvement of regional lymph nodes is a major prognostic factor of colorectal cancer, which influences also its treatment strategy. International consensus foresees retrieval of ≥12 lymph nodes from colorectal specimens. The aim of the study was to assess the effect of intra-arterial staining of colorectal specimens with methylene blue on lymph node harvest. A total of 266 radically operated colorectal cancer patients were randomized into the methylene blue staining and non-staining groups. In the staining group, methylene blue solution was injected into the colorectal specimen's artery after its removal. The specimens were analysed for lymph node count, diameter and metastatic involvement. The median number of lymph nodes was higher in the staining group, 27 (95% CI 23-31%), compared with the control group, 16 (95% CI 14-19, p Methylene blue staining improves significantly staging accuracy through finding more small-diameter lymph nodes. It enables to detect ≥12 lymph nodes in the majority of cases. We recommend routine use of this technique in all colorectal resections with curative intent. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  5. Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

    Directory of Open Access Journals (Sweden)

    Maria Carolina Witkowski

    2013-12-01

    Full Text Available OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG and intermittent infusion group (IIG. The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22 months, and 77 (55% were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours when compared to IIG (5.3±3.5mL/24 hours with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031].

  6. Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

    Science.gov (United States)

    Witkowski, Maria Carolina; de Moraes, Maria Antonieta P.; Firpo, Cora Maria F.

    2013-01-01

    OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG) and intermittent infusion group (IIG). The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22) months, and 77 (55%) were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours) when compared to IIG (5.3±3.5mL/24 hours) with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031]. PMID:24473958

  7. Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats

    Energy Technology Data Exchange (ETDEWEB)

    Egawa, H.; Maki, A.; Mori, K.; Yamamoto, Y.; Mitsuhashi, S.; Bannai, K.; Asano, K.; Ozawa, K. (Kyoto Univ. (Japan))

    1990-06-01

    Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra-arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)-LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using (14C, 3H)KM2210-LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor-to-normal-liver and tumor-to-blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer.

  8. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    Energy Technology Data Exchange (ETDEWEB)

    Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

    2015-07-15

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  9. Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer.

    Science.gov (United States)

    Jeon, Min Jeong; Gordon, Andrew C; Larson, Andrew C; Chung, Jin Wook; Kim, Young Il; Kim, Dong-Hyun

    2016-05-01

    A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death.

  10. Hepatic intra-arterial infusion of yttrium-90 microspheres in the treatment of recurrent hepatocellular carcinoma after liver transplantation: A case report

    Institute of Scientific and Technical Information of China (English)

    Louis Rivera; Huan Giap; William Miller; Jonathan Fisher; Donald J Hillebrand; Christopher Marsh; Randolph L Schaffer

    2006-01-01

    Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after liver transplantation.Recurrence is associated witha mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemoembolization (TACE), radiofrequency ablation (RFA),ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma.Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres (SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA). Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein (AFP) level. There were no adverse consequences of initial treatment.

  11. Revisiting intra-arterial drug delivery for treating brain diseases or is it "déjà-vu, all over again"?

    Directory of Open Access Journals (Sweden)

    Shailendra Joshi

    2014-01-01

    Full Text Available For over six decades intra-arterial (IA drugs have been sporadically used for the treatment of lethal brain diseases. In recent years considerable advance has been made in the IA treatment of retinoblastomas, liver and locally invasive breast cancers, but relatively little progress has been made in the treatment of brain cancers. High resting blood flow and the presence of the blood-brain barrier (BBB, makes IA delivery to the brain tissue far more challenging, compared to other organs. The lack of advance in the field is also partly due to the inability to understand the complex pharmacokinetics of IA drugs as it is difficult to track drug concentrations in sub-second time frame by conventional chemical methods. The advances in optical imaging now provide unprecedented insights into the pharmacokinetics of IA drug and optical tracer delivery. Novel delivery methods, improved IA drug formulations, and optical pharmacokinetics, present us with untested paradigms in pharmacology that could lead to new therapeutic interventions for brain cancers and stroke. The object of this review is to bring into focus the current practice, problems, and the potential of IA drug delivery for treating brain diseases. A concerted effort is needed at basic sciences (pharmacology and drug imaging, and translational (drug delivery techniques and protocol development levels by the interventional neuroradiology community to advance the field.

  12. Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma.

    Science.gov (United States)

    Park, Wooram; Chen, Jeane; Cho, Soojeong; Park, Sin-Jung; Larson, Andrew C; Na, Kun; Kim, Dong-Hyun

    2016-05-25

    Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug-eluting beads (DEB) were developed for transcatheter IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. It can be difficult to control drug loading/release from DEB and to monitor selective delivery to the targeted tumors. Embolized DEBs in hepatic arteries frequently induce hypoxic and low pH conditions, promoting cancer cell growth. In this study, an acidic pH-triggered drug-eluting nanocomposite (pH-DEN) including superparamagnetic iron oxide nanocubes and pH-responsive synthetic peptides with lipid tails [octadecylamine-p(API-l-Asp)10] was developed for magnetic resonance imaging (MRI)-monitored transcatheter delivery of sorafenib (the only FDA-approved systemic therapy for liver cancer) to HCC. The synthesized sorafenib-loaded pH-DENs exhibited distinct pH-triggered drug release behavior at acidic pH levels and highly sensitive MR contrast effects. In an orthotopic HCC rat model, successful hepatic IA delivery and distribution of sorafenib-loaded pH-DEN was confirmed with MRI. IA-delivered sorafenib-loaded pH-DENs elicited significant tumor growth inhibition in a rodent HCC model. These results indicate that the sorafenib-pH-DENs platform has the potential to be used as an advanced tool for liver-directed IA treatment of unresectable HCC.

  13. Carboplatin treatment of antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

    2012-01-01

    Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...

  14. Adaptive Randomization of Veliparib–Carboplatin Treatment in Breast Cancer

    Science.gov (United States)

    Rugo, Hope S.; Olopade, Olufunmilayo I.; DeMichele, Angela; Yau, Christina; van ‘t Veer, Laura J.; Buxton, Meredith B.; Hogarth, Michael; Hylton, Nola M.; Paoloni, Melissa; Perlmutter, Jane; Symmans, W. Fraser; Yee, Douglas; Chien, A. Jo; Wallace, Anne M.; Kaplan, Henry G.; Boughey, Judy C.; Haddad, Tufia C.; Albain, Kathy S.; Liu, Minetta C.; Isaacs, Claudine; Khan, Qamar J.; Lang, Julie E.; Viscusi, Rebecca K.; Pusztai, Lajos; Moulder, Stacy L.; Chui, Stephen Y.; Kemmer, Kathleen A.; Elias, Anthony D.; Edmiston, Kirsten K.; Euhus, David M.; Haley, Barbara B.; Nanda, Rita; Northfelt, Donald W.; Tripathy, Debasish; Wood, William C.; Lyandres, Julia; Davis, Sarah E.; Hirst, Gillian L.; Sanil, Ashish; Berry, Donald A.; Esserman, Laura J.

    2017-01-01

    Background I-SPY 2 is a phase 2 standing multicenter platform trial designed to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to matching experimental regimens with responding patient subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin (VC). Methods Eligible women had ≥2.5 cm stage II/III breast cancer, categorized into 8 biomarker subtypes based on HER2, hormone-receptor status (HR) and MammaPrint. Patients are adaptively randomized within subtype to better performing regimens compared to standard therapy (control). Regimens are evaluated within 10 signatures, prospectively defined combinations of subtypes. VC plus standard therapy was considered for HER2-negative tumors and therefore evaluated in 3 signatures. The primary endpoint of I-SPY 2 is pathologic complete response (pCR). MR volume changes during treatment inform the likelihood that a patient will achieve pCR. Regimens graduate if and when they have a high (Bayesian) predictive probability of success in a subsequent phase 3 neoadjuvant trial within the graduating signature. Results VC graduated in triple-negative breast cancer with 88% predicted probability of phase 3 success. A total of 72 patients were randomized to VC and 44 to concurrent controls. Respective pCR estimates (95% probability intervals) were 51% (35%–69%) vs 26% (11%–40%). Greater toxicity of VC was manageable. Conclusion The design of I-SPY 2 has the potential to efficiently identify responding tumor subtypes for the various therapies being evaluated. VC added to standard therapy improves pCR rates specifically in triple-negative breast cancer. PMID:27406347

  15. In connection with the publication in Bali Med J 2016, Volume 5, Number 2: 25-29, entitled "Intra-Arterial Heparin Flushing Increases Manual Muscle Test – Medical Research Councils (MMT-MRC Score in Chronic Ischemic Stroke Patient "

    Directory of Open Access Journals (Sweden)

    Moh Hasan Machfoed

    2016-06-01

    Full Text Available  In connection with the publication in Bali Med J 2016, Volume 5, Number 2: 25-29, entitled "Intra-Arterial Heparin Flushing Increases Manual Muscle Test – Medical Research Councils (MMT-MRC Score in Chronic Ischemic Stroke Patient ", herewith, please allow us to do reviews of the study discussion. By assessing the discussion, it can be proved whether there are references that support the results of study.

  16. Intra-arterial MR-angiography on an open-bore MR-scanner compared to digital-subtraction angiography of the infra-popliteal runoff in patients with peripheral arterial occlusive disease

    Energy Technology Data Exchange (ETDEWEB)

    Huegli, Rolf W. [Department of Radiology University Hospital of Basel, Petersgraben 4, 4031 Basel (Switzerland)], E-mail: rhuegli@uhbs.ch; Thalhammer, Christoph [Department of Angiology, University Hospital of Basel, Petersgraben 4, 4031 Basel (Switzerland)], E-mail: cthalhammer@uhbs.ch; Jacob, Augustinus L. [Department of Radiology University Hospital of Basel, Petersgraben 4, 4031 Basel (Switzerland)], E-mail: ajacob@uhbs.ch; Jaeger, Kurt [Department of Angiology, University Hospital of Basel, Petersgraben 4, 4031 Basel (Switzerland)], E-mail: kjaeger@uhbs.ch; Bilecen, Deniz [Department of Radiology University Hospital of Basel, Petersgraben 4, 4031 Basel (Switzerland)], E-mail: dbilecen@uhbs.ch

    2008-06-15

    Purpose: To evaluate the diagnostic value of contrast-enhanced intra-arterial 3D-MR-angiography (IA-MRA) of the infra-popliteal arteries in an open-bore magnet. Number, severity of arterial lesions, and artefacts were compared to routinely performed intra-arterial digital-subtraction angiography (IA-DSA) in patients suffering from symptomatic peripheral arterial occlusive disease (PAOD). Material and methods: Fifteen patients admitted for PAOD underwent percutaneous transluminal angioplasty (PTA) by IA-DSA. After PTA, IA-MRA of the infra-popliteal station was performed on an open-bore 1.5 T MR-scanner applying a low dose intra-arterial contrast-enhanced 3D-gradient-echo-MRA with gadopentate dimeglumine. The reading was performed by three blinded readers distinguishing moderate ({<=}50%), significant stenoses (51-99%) and vessel occlusions. Imaging artefacts were recorded and binary classified as not disturbing or compromising the observation of the arterial tree. Results: Overall IA-DSA revealed 36 moderate stenoses ({<=}50%), 38 significant stenoses (51-99%), and 10 vessel occlusions. For the detection of significant stenoses and occlusions, the overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of IA-MRA were 96%, 83%, 88%, 94% and 90%. The only observed artefact was venous overlay in four stations. The readout was not hampered in any case. Conclusion: Intra-arterial contrast-enhanced 3D-gradient-echo-MRA on an open-bore MR-scanner offers an acceptable diagnostic accuracy in diagnosing peripheral arterial occlusive disease in the infra-popliteal region and correlates well with DSA.

  17. Quantification and clinical application of carboplatin in plasma ultrafiltrate.

    Science.gov (United States)

    Downing, Kim; Jensen, Berit Packert; Grant, Sue; Strother, Matthew; George, Peter

    2017-05-10

    Carboplatin is a chemotherapy drug used in a variety of cancers with the primary toxicity being exposure-dependant myelosuppression. We present the development and validation of a simple, robust inductively coupled plasma mass spectrometry (ICP-MS) method to measure carboplatin in plasma ultrafiltrate. Plasma ultrafiltrates samples were prepared using Amicon Ultra 30,000da cut-off filters and then diluted with ammonia EDTA before ICP-MS analysis. The assay was validated in the range 0.19-47.5mg/L carboplatin in ultrafiltrate. The assay was linear (r(2)>0.9999), accurate (plasma ultrafiltrate and aqueous platinum calibrators and recovery was complete. The assay was applied to 10 clinical samples from patients receiving carboplatin. Incurred sample reanalysis showed reproducible values over 3 analysis days (plasma stability prior to ultrafiltration has been a major concern in previous clinical studies this was studied extensively at room temperature (22°C) over 24h. Carboplatin was found to be stable in both spiked plasma (n=3) and real patient samples (n=10) at room temperature for up to 8h before ultrafiltration. This makes routine measurement of carboplatin concentrations in clinical settings feasible. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Carboplatin hypersensitivity in children with glial tumors: a report of two cases

    Directory of Open Access Journals (Sweden)

    Tugce Kazgan

    2016-12-01

    Full Text Available Carboplatin, commonly used chemotherapeutic agent in treatment of pediatric cancers, can cause life-threatening hypersensitivty reactions. Carboplatin hypersensitivity is protocol-specific and associated with repeated doses and prolonged use of the drug. Vincristin and carboplatin combination is used efficiently in treatment of pediatric low-grade gliomas. However, hypersensitivity reactions are frequently observed during usage of this protocol. Desensitization strategies with variable success rates were reported. Failure of these strategies may lead to cessation of carboplatin Here, we report two cases with carboplatin hypersensitivity treated with epinephrine administration, in whom carboplatin was discontinued after hypersensitivity reaction. [Cukurova Med J 2016; 41(4.000: 796-798

  19. Carboplatin plus VP-16 with simultaneous radiotherapy in the treatment of non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Imanaka, Kazufumi; Kodama, Akihisa; Okamoto, Yoshiaki; Izumiyama, Kazutaka; Sakaguchi, Toshiya; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1995-01-01

    Ten patients with non-small cell lung cancer were treated by concurrent chemoradiotherapy. The protocol consists of split course radiotherapy and simultaneous chemotherapy (carboplatin plus VP-16). All patients tolerated well this treatment with no life-threatening complications and treatment duration was shortened compared to that of sequential chemoradiotherapy. Response rate was 50% (CR: 1, PR: 4), median survival time was 12.8 months and 2-year survival rate was 20%. The major toxicity was leucopenia, with WHO grade 4 leucopenia in 3 patients and grade 3 in 3 patients. This protocol was considered to be tolerable and effective for the treatment of non-small cell lung cancer. (author).

  20. Concurrency engineering

    NARCIS (Netherlands)

    Jesshope, C.; Shafarenko, A.

    2008-01-01

    This is a discussion paper on a very important topic that is about to become mainstream. It deals with the issues of software engineering in concurrent systems. It introduces this topic and illustrates the arguments for a change of perspective. It underlines these arguments with two examples, an

  1. Intra-Arterial Delivery of Bevacizumab after Blood-Brain Barrier Disruption for the Treatment of Recurrent Glioblastoma: Progression-Free Survival and Overall Survival

    Science.gov (United States)

    Burkhardt, Jan-Karl; Riina, Howard; Shin, Benjamin J.; Christos, Paul; Kesavabhotla, Kartik; Hofstetter, Christoph P.; Tsiouris, Apostolos John; Boockvar, John A.

    2013-01-01

    BACKGROUND This prospective, single-center study assesses progression-free survival (PFS) and overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) treated with a single dose of superselective intra-arterial cerebral infusion (SIACI) of bevacizumab (BV) after blood-brain barrier disruption (BBBD). Patients were initially enrolled in our phase I study, for which the primary end point was to determine the safety and maximum tolerated dose of SIACI BV. METHODS Fourteen patients with recurrent GBM were recruited between August 2009 and November 2010 after failing the standard treatment with radiation therapy and temozolomide. None of these patients were previously treated with BV. After receiving a single dose of IA BV (2 to 15 mg/kg), standard IV BV chemotherapy was continued in 12 of 14 patients (86%). The recently updated Response Assessment in Neuro-Oncology Working Group (RANO) criteria were used to evaluate PFS, and the Kaplan-Meier estimator was used to evaluate PFS and OS. RESULTS Using RANO criteria, the median PFS in these patients was 10 months. The median OS estimation for this cohort was 8.8 months. The OS was less than the PFS because 4 patients died without progressing. Toxicity attributed to the IA BV treatment was present in 2 patients (wound dehiscence and rash). Another patient suffered from seizures 1 week after the SIACI procedure; however, this patient had epilepsy before and seizure type/frequency were similar before and after therapy. CONCLUSIONS Our study shows that for patients naïve to BV, a single dose of SIACI BV after BBBD followed by IV BV offers an encouraging outcome in terms of PFS when compared with previous trials using IV BV with and without concomitant irinotecan (CPT-11). Larger phase II trials are warranted to determine whether repeated IA BV alone is superior to IV BV for recurrent GBM. PMID:22405392

  2. Study of the stability of packaging and storage conditions of human mesenchymal stem cell for intra-arterial clinical application in patient with critical limb ischemia.

    Science.gov (United States)

    Gálvez-Martín, Patricia; Hmadcha, Abdelkrim; Soria, Bernat; Calpena-Campmany, Ana C; Clares-Naveros, Beatriz

    2014-04-01

    Critical limb ischemia (CLI) is associated with significant morbidity and mortality. In this study, we developed and characterized an intra-arterial cell suspension containing human mesenchymal stem cells (hMSCs) for the treatment of CLI. Equally, the stability of cells was studied in order to evaluate the optimal conditions of storage that guarantee the viability from cell processing to the administration phase. Effects of various factors, including excipients, storage temperature and time were evaluated to analyze the survival of hMSCs in the finished medicinal product. The viability of hMSCs in different packaging media was studied for 60 h at 4 °C. The best medium to maintain hMSCs viability was then selected to test storage conditions (4, 8, 25 and 37 °C; 60 h). The results showed that at 4 °C the viability was maintained above 80% for 48 h, at 8 °C decreased slightly, whereas at room temperature and 37 °C decreased drastically. Its biocompatibility was assessed by cell morphology and cell viability assays. During stability study, the stored cells did not show any change in their phenotypic or genotypic characteristics and physicochemical properties remained constant, the ability to differentiate into adipocytes and osteocytes and sterility requirements were also unaltered. Finally, our paper proposes a packing media composed of albumin 20%, glucose 5% and Ringer's lactate at a concentration of 1×10(6) cells/mL, which must be stored at 4 °C as the most suitable to maintain cell viability (>80%) and without altering their characteristics for more than 48 h.

  3. Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy.

    Science.gov (United States)

    Yanagie, Hironobu; Dewi, Novriana; Higashi, Syushi; Ikushima, Ichiro; Seguchi, Koji; Mizumachi, Ryoji; Murata, Yuji; Morishita, Yasuyuki; Shinohara, Atsuko; Mikado, Shoji; Yasuda, Nakahiro; Fujihara, Mitsuteru; Sakurai, Yuriko; Mouri, Kikue; Yanagawa, Masashi; Iizuka, Tomoya; Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shin-Ichiro; Tanaka, Hiroki; Matsukawa, Takehisa; Yokoyama, Kazuhito; Fujino, Takashi; Ogura, Koichi; Nonaka, Yasumasa; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Yui, Sho; Nishimura, Ryohei; Ono, Koji; Takamoto, Sinichi; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Hasumi, Kenichiro; Takahashi, Hiroyuki

    2017-06-01

    Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a (10)BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. We prepared the (10)BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 10(12) n cm(-2). Morphological and pathological analyses were performed on Day 14 after neutron irradiation. Biodistribution results have revealed that (10)B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with (10)BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the (10)BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped (10)BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure.

  4. MRI after implantation of a novel femoral closure device following intra-arterial catheterisation: implications for subsequent contrast-enhanced MR angiography.

    Science.gov (United States)

    Mohrs, Oliver K; Petersen, Steffen E; Nowak, Bernd; Kauczor, Hans-Ulrich; Voigtlaender, Thomas

    2010-05-01

    To assess MRI safety aspects and artefacts of a novel femoral artery closure device during contrast-enhanced MR angiography in patients following intra-arterial catheterisation. Ten consecutive patients underwent MRI within 24 h of coronary angiography and placement of a femoral artery closure device. We used a T2-weighted gradient-echo MRI sequence to measure the device-related artefact size in comparison with a phantom image, phase-contrast flow measurement proximal to, at the level of and distal to the device to quantify potential differences in flow velocity and contrast-enhanced 3D gradient-echo MR angiography to differentiate potential femoral artery stenosis from device-related artefacts. The mean size of the oval-shaped artefact was 8.4 x 6.6 mm (+/-1.0 x 0.8 mm) and was almost identical to the maximum artefact size of the phantom measurement (8.3 x 5.7 mm). Device placement did not result in an increased peak velocity (proximal 69 +/- 23 cm/s, at the level of 64 +/- 11 cm/s and distal to the device 63 +/- 12 cm/s, p = 0.67). The mean artefact penetration into the vessel lumen was 0.5 +/- 0.5 mm (percentage vessel narrowing 7.0 +/- 6%; range 0-16%). The MR conditional StarClose femoral artery closure device was used safely within 24 h of deployment at 1.5 T. Despite clip-related artefacts MR angiography will allow for easy differentiation of clip-related artefacts from high-grade atherosclerotic stenosis.

  5. MRI after implantation of a novel femoral closure device following intra-arterial catheterisation: implications for subsequent contrast-enhanced MR angiography

    Energy Technology Data Exchange (ETDEWEB)

    Mohrs, Oliver K. [University of Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany); Darmstadt Radiology, Department of Cardiovascular Imaging at Alice-Hospital, Darmstadt (Germany); Petersen, Steffen E. [The London Chest Hospital, William Harvey Research Institute, Centre Lead for Advanced Cardiovascular Imaging, London (United Kingdom); Nowak, Bernd; Voigtlaender, Thomas [Cardiovascular Center Bethanien (CCB), Frankfurt/Main (Germany); Kauczor, Hans-Ulrich [University of Heidelberg, Department of Diagnostic and Interventional Radiology, Heidelberg (Germany)

    2010-05-15

    To assess MRI safety aspects and artefacts of a novel femoral artery closure device during contrast-enhanced MR angiography in patients following intra-arterial catheterisation. Ten consecutive patients underwent MRI within 24 h of coronary angiography and placement of a femoral artery closure device. We used a T2-weighted gradient-echo MRI sequence to measure the device-related artefact size in comparison with a phantom image, phase-contrast flow measurement proximal to, at the level of and distal to the device to quantify potential differences in flow velocity and contrast-enhanced 3D gradient-echo MR angiography to differentiate potential femoral artery stenosis from device-related artefacts. The mean size of the oval-shaped artefact was 8.4 x 6.6 mm ({+-}1.0 x 0.8 mm) and was almost identical to the maximum artefact size of the phantom measurement (8.3 x 5.7 mm). Device placement did not result in an increased peak velocity (proximal 69 {+-} 23 cm/s, at the level of 64 {+-} 11 cm/s and distal to the device 63 {+-} 12 cm/s, p = 0.67). The mean artefact penetration into the vessel lumen was 0.5 {+-} 0.5 mm (percentage vessel narrowing 7.0 {+-} 6%; range 0-16%). The MR conditional StarClose femoral artery closure device was used safely within 24 h of deployment at 1.5 T. Despite clip-related artefacts MR angiography will allow for easy differentiation of clip-related artefacts from high-grade atherosclerotic stenosis. (orig.)

  6. Patterns of intra-arterial blood pressure monitoring for patients undergoing total shoulder arthroplasty under general anesthesia: a retrospective analysis of 23,073 patients.

    Science.gov (United States)

    Gabriel, Rodney A; Beverly, Anair; Dutton, Richard P; Urman, Richard D

    2016-10-13

    Total shoulder arthroplasty (TSA) is typically performed in the beach-chair position. Maintenance of adequate mean arterial pressure is required to provide appropriate cerebral perfusion pressure and prevent cerebral ischemia. Placement of an arterial line to facilitate invasive monitoring is discretionary, based on clinical judgment. We aimed to describe patient, surgical and institutional factors associated with the current use of blood pressure monitoring via an arterial line for TSA. We used de-identified patient data from the National Anesthesia Clinical Outcomes Registry between 2010 and 2015 to identify patients undergoing TSA under general anesthesia. We conducted a multivariable logistic regression model to demonstrate factors significantly associated with arterial line placement. We report results as odds ratios (OR) with their associated 95 % confidence intervals (CI). Of 23,073 patients undergoing TSA under general anesthesia, 443 (1.92 %) had intra-arterial blood pressure monitoring. Patient age over 65 years old (OR 1.74, CI 1.37-2.21), congestive heart failure (OR 7.09, CI 2.63-19.14) and surgery lasting at least 180 min (OR 4.10, CI 3.33-5.05) were all associated with increased odds for arterial line placement. Compared to university hospitals, arterial line placement was more likely in attached or freestanding surgical centers (OR 2.01, CI 1.37-2.96) and less likely in medium sized community hospitals (OR 0.62, CI 0.42-0.93), small community hospitals (OR 0.11, CI 0.03-0.34) and facilities performing less than 100 TSAs per year (OR 0.19, CI 0.12-0.31). Utilization of arterial line monitoring for TSA has associations with both institutional and patient factors. This study demonstrates the national patterns for the use of arterial lines for TSA and may serve as a resource to aid in clinical judgment.

  7. Initial clinical experience with near-infrared spectroscopy in assessing cerebral tissue oxygen saturation in cerebral vasospasm before and after intra-arterial verapamil injection.

    Science.gov (United States)

    Meng, Lingzhong; Settecase, Fabio; Xiao, Jifang; Yu, Zhaoxia; Flexman, Alana M; Higashida, Randall T

    2016-04-01

    Cerebral vasospasm is a devastating complication after subarachnoid hemorrhage. The use of cerebral tissue oxygen saturation (SctO2) to non-invasively assess changes in cerebral tissue perfusion induced by intra-arterial (IA) verapamil treatment has not been described to our knowledge. A total of 21 consecutive post-craniotomy patients scheduled for possible IA verapamil treatment of cerebral vasospasm were recruited. The effect of IA verapamil injection on SctO2 being continuously monitored on both the left and right forehead was investigated. Comparisons between changes in SctO2 monitored on the ipsilateral and contralateral forehead in relationship to the side of internal carotid artery (ICA) injection were performed. A total of 47 IA verapamil injections (15 left ICA, 18 right ICA, and 14 vertebral artery injections) during 18 neurointerventional procedures in 13 patients were analyzed. IA verapamil administration led to both increases and decreases in SctO2. Changes in SctO2 ipsilateral to the ICA injection side were more pronounced (p=0.02 and 0.07 for left and right ICA injections, respectively) and favored compared to contralateral SctO2 changes. We were unable to obtain reliable measurements on the side ipsilateral to the craniotomy during four procedures in three patients, presumably secondary to pneumocephalus. The local cerebral vasodilating effect of IA verapamil injection is suggested by the differential changes in SctO2 ipsilateral and contralateral to the ICA injection side. The inconsistent changes in SctO2 and the limitations of applying cerebral oximetry in this patient population needs to be recognized.

  8. A Population-Based Clinical Trial of Irinotecan and Carboplatin

    Directory of Open Access Journals (Sweden)

    Derick Lau

    2009-01-01

    Full Text Available Purpose. Phase I trials of anticancer drugs are commonly conducted using the method of modified Fibonacci. We have developed a population-based design for phase I trials of combining anticancer drugs such as irinotecan and carboplatin. Patients and Methods. Intrapatient dose escalation of irinotecan and carboplatin was performed according to a predetermined schema to reach individual dose-limiting toxicity (DLT in 50 patients with solid tumors refractory to previous chemotherapy. The individual toxicity-limiting dose levels were analyzed for normal distribution using the method of Ryan-Joiner and subsequently used to determine a population-based maximum tolerated dose (pMTD. For comparison, a simulation study was performed using the method of modified Fibonacci. Results. The most common dose-limiting toxicities (DLTs included neutropenia (58%, thrombocytopenia (16%, and diarrhea (8%. The frequency of individual toxicity-limiting dose levels of 50 patients approximated a normal distribution. The dose levels associated with individual limiting toxicities ranged from level 1 (irinotecan 100 mg/m2 and carboplatin AUC = 4 mg/mL x min to level 8 (irinotecan 350 mg/m2 and carboplatin AUC = 6. The pMTD was determined to be dose level 3 (150 mg/m2 for irinotecan and AUC = 5 for carboplatin. In contrast, the MTD was determined to be dose level 4 (200 mg/m2 for irinotecan and AUC 5 for carboplatin by modified-Fibonacci simulation. Conclusions. The population-based design of phase I trial allows optimization of dose intensity and derivation of a pMTD. The pMTD has been applied in phase II trial of irinotecan and carboplatin in patients with small-cell lung cancer.

  9. Concurrent chemoradiotherapy for advanced cervical cancer. A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Kodama, Junichi; Hashimoto, Ichiro; Seki, Noriko; Hongo, Atsushi; Mizutani, Yasushi; Miyagi, Yasunari; Yoshinouchi, Mitsuo; Kudo, Takafumi [Okayama Univ. (Japan). School of Medicine

    2001-03-01

    Recently, attempts have made to use radiotherapy in combination with chemotherapy in various solid tumors including cervical cancer. Twenty-four patients with locally advanced cervical cancer were treated with concurrent Carboplatin (16-24 mg/m{sup 2}/day) or Nedaplatin (20 mg/m{sup 2}/week) and conventional radiotherapy. Of 13 evaluable patients, there were nine complete responders and four partial responders. There was no renal damage or grade 4 hematological toxicity. Gastrointestinal adverse reactions were mild. One patient had grade 3 dermatologic toxicity after delayed radiation therapy. This pilot study suggests that daily Carboplatin or weekly Nedaplatin administered with standard radiation therapy is safe, well-tolerated, and thus may be useful as a radiation sensitizer in the treatment of locally advanced cervical cancer. (author)

  10. Concurrent Collections

    OpenAIRE

    Zoran Budimlić; Michael Burke; Vincent Cavé; Kathleen Knobe; Geoff Lowney; Ryan Newton; Jens Palsberg; David Peixotto; Vivek Sarkar; Frank Schlimbach; Sağnak Taşırlar

    2010-01-01

    We introduce the Concurrent Collections (CnC) programming model. CnC supports flexible combinations of task and data parallelism while retaining determinism. CnC is implicitly parallel, with the user providing high-level operations along with semantic ordering constraints that together form a CnC graph. We formally describe the execution semantics of CnC and prove that the model guarantees deterministic computation. We evaluate the performance of CnC implementations on several applications an...

  11. Dose adjustment of carboplatin in patients on hemodialysis.

    Science.gov (United States)

    Guddati, Achuta K; Joy, Parijat S; Marak, Creticus P

    2014-03-01

    Carboplatin is one of the most prescribed cytotoxic drug, which is extensively used in the treatment regimens of several malignancies. The therapeutic efficiency of carboplatin has been found to correlate the area under curve (AUC). The Calvert formula has been extensively used to determine the dose of carboplatin for a fixed AUC and glomerular filtration rate (GFR). This formula has also been used in patients with end-stage renal disease on hemodialysis by assuming that the GFR is zero. This is applicable to patients who receive hemodialysis within 12-18 h after carboplatin infusion. After the first 24 h, a majority of the carboplatin is bound to proteins is not easily dialyzable and hence continues to remain in the blood stream despite repeated sessions of hemodialysis. We derive a correction factor to calculate the resultant AUC in such patients. The analysis done by using this correction factor shows that the AUC can increase by eightfold in patients who received the adjusted dose but whose hemodialysis was delayed beyond 24 h after infusion. The correction factor proposed here can also be used to calculate the dose adjustment required a priori in patients who may receive delayed hemodialysis. It is also useful to predict the AUC and estimate the resultant toxicity in such patients.

  12. Carboplatin-associated ototoxicity in children with retinoblastoma.

    Science.gov (United States)

    Qaddoumi, Ibrahim; Bass, Johnnie K; Wu, Jianrong; Billups, Catherine A; Wozniak, Amy W; Merchant, Thomas E; Haik, Barrett G; Wilson, Matthew W; Rodriguez-Galindo, Carlos

    2012-04-01

    Carboplatin-induced ototoxicity remains poorly defined but is of potential great consequence in children with retinoblastoma. We retrospectively assessed the incidence of ototoxicity and its risk factors in children with retinoblastoma who were treated with carboplatin. We reviewed the audiologic test results of 60 patients with retinoblastoma who received front-line treatment with systemic carboplatin and vincristine according to the St Jude RET-3 protocol (n = 23) or best clinical management (n = 37). Ototoxicity was evaluated by three different grading systems. Twelve patients (20%) developed ototoxicity at some time after treatment initiation; however, ototoxicity resolved in two patients, and thus,10 patients (17%) had sustained hearing loss as documented at their most recent audiologic evaluation. Nine of these 10 patients had grade 3 or 4 ototoxicity, and nine patients were less than 6 months of age at the start of chemotherapy. Age at the start of chemotherapy was the only risk factor identified as a significant predictor of sustained hearing loss. Younger age was associated with an increased incidence of hearing loss. The different ototoxicity grading systems showed good overall agreement in the identification of patients with ototoxicity. Agreement was greatest between the Brock and Children's Cancer Group systems. We found that young patients with retinoblastoma who were treated with systemic carboplatin had a higher incidence of ototoxicity than previously reported. Younger patients (ototoxicity than were older patients. Children treated with carboplatin should routinely undergo thorough, long-term audiologic monitoring.

  13. Concurrent Collections

    Directory of Open Access Journals (Sweden)

    Zoran Budimlić

    2010-01-01

    Full Text Available We introduce the Concurrent Collections (CnC programming model. CnC supports flexible combinations of task and data parallelism while retaining determinism. CnC is implicitly parallel, with the user providing high-level operations along with semantic ordering constraints that together form a CnC graph. We formally describe the execution semantics of CnC and prove that the model guarantees deterministic computation. We evaluate the performance of CnC implementations on several applications and show that CnC offers performance and scalability equivalent to or better than that offered by lower-level parallel programming models.

  14. Tumor Uptake of Hollow Gold Nanospheres after Intravenous and Intra-arterial Injection: PET/CT Study in a Rabbit VX2 Liver Cancer Model

    Science.gov (United States)

    Tian, Mei; Lu, Wei; Zhang, Rui; Xiong, Chiyi; Ensor, Joe; Nazario, Javier; Jackson, James; Shaw, Colette; Dixon, Katherine A.; Miller, Jennifer; Wright, Kenneth; Li, Chun; Gupta, Sanjay

    2014-01-01

    Purpose This study was designed to investigate the intratumoral uptake of hollow gold nanospheres (HAuNS) after hepatic intra-arterial (IA) and intravenous (IV) injection in a liver tumor model. Materials and Methods Fifteen VX2 tumor-bearing rabbits were randomized into five groups (N=3 in each group) that received either IV 64Cu-labeled PEG-HAuNS (IV-PEG-HAuNS), IA 64Cu-labeled PEG-HAuNS (IA-PEG-HAuNS), IV cyclic peptide (RGD)-conjugated 64Cu-labeled PEG-HAuNS (IV-RGD-PEG-HAuNS), IA RGD-conjugated 64Cu-labeled PEG-HAuNS (IA-RGD-PEG-HAuNS), or IA 64Cu-labeled PEG-HAuNS with lipiodol (IA-PEG-HAuNS-lipiodol). The animals underwent PET/CT 1 hour after injection, and uptake expressed as percentage of injected dose per gram of tissue (%ID/g) was measured in tumor and major organs. The animals were euthanized 24 hours after injection, and tissues were evaluated for radioactivity. Results At 1 hour after injection, animals in the IA-PEG-HAuNS-lipiodol group showed significantly higher tumor uptake (P < 0.001) and higher ratios of tumor-to-normal liver uptake (P < 0.001) than those in all other groups. The biodistribution of radioactivity 24 hours after injection showed that IA delivery of PEG-HAuNS with lipiodol resulted in the highest tumor uptake (0.33 %ID/g; P < 0.001) and tumor-to-normal liver ratio (P < 0.001) among all delivery methods. At 24 hours, the IA-RGD-PEG-HAuNS group showed higher tumor uptake than the IA-PEG-HAuNS group (0.20 %ID/g vs. 0.099 %ID/g; P < 0.001). Conclusion Adding iodized oil to IA-PEG-HAuNS maximizes nanoparticle delivery to hepatic tumors and therefore may be useful in targeted chemotherapy and photoablative therapy. PET/CT can be used to noninvasively monitor the biodistribution of radiolabeled HAuNS after IV or IA injection. PMID:23608932

  15. Type I interferon receptor in peripheral blood mononuclear cells may predict response to intra-arterial 5-fluorouracil + interferon therapy for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Korenaga K

    2011-04-01

    Full Text Available Yasuyuki Tomiyama1, Naoko Yoshioka1, Yoshiaki Yanai2,3, Tomoya Kawase1, Sohji Nishina1, Yuichi Hara1, Koji Yoshida1, Keiko Korenaga1, Masaaki Korenaga1, Keisuke Hino11Department of Hepatology and Pancreatology, Kawasaki Medical University, Kurashiki, Japan; 2Institute of Fujisaki, Hayashibara Biochemical Lab Inc, Okayama, Japan; 3Pharmaceutical Marketing Division, Otsuka Pharmaceutical Co Ltd, Tokyo, JapanBackground: Type 1 interferon alpha receptor 2 (IFNAR2 in the liver has been reported to be a predictive factor for the response to intra-arterial 5-fluorouracil (5-FU + systemic interferon (IFN-alpha combination therapy in patients with advanced hepatocellular carcinoma. We tested whether IFNAR2 expression in peripheral blood mononuclear cells could predict the response to 5-FU + IFN.Methods: Predictive factors for survival and response to therapy were determined in 30 patients with advanced hepatocellular carcinoma who underwent treatment with 5-FU + IFN. IFNAR2 expression in peripheral blood mononuclear cells was measured in 11 of the 30 patients.Results: With a mean number of 4.2 courses of combination therapy, one patient (3% showed a complete response, eight (27% showed partial responses, 13 (43% had stable disease, and eight (27% showed progressive disease. The median survival time of responders (complete response/partial response was 12.7 months and that of nonresponders (stable disease/progressive disease was 7.5 months. The one-year and two-year cumulative survival rates of responders and nonresponders were 87/69% and 40/11%, respectively (P = 0.019. Multivariate analysis identified response to therapy (P = 0.037 as the sole independent determinant of survival. The expression level of IFNAR2 in peripheral blood mononuclear cells was significantly (P = 0.012 higher in responders (6.5 ± 2.4 than in nonresponders (2.4 ± 0.6, even though no clinical factors were identified as being associated with the response to the combination

  16. Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice.

    Science.gov (United States)

    Ganguly, Koustav; Ettehadieh, Dariusch; Upadhyay, Swapna; Takenaka, Shinji; Adler, Thure; Karg, Erwin; Krombach, Fritz; Kreyling, Wolfgang G; Schulz, Holger; Schmid, Otmar; Stoeger, Tobias

    2017-06-20

    The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardio-vascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM. Equivalent surface area CNP doses in the blood (30mm(2) per animal) were applied by IAI or inhalation (lung-deposited dose 10,000mm(2); accounting for 0.3% of lung-to-blood CNP translocation). Mice were analyzed for changes in hematology and molecular markers of endothelial/epithelial dysfunction, pro-inflammatory reactions, oxidative stress, and coagulation in lungs and extra-pulmonary organs after CNP inhalation (4 h and 24 h) and CNP infusion (4 h). For methodological reasons, we used two different CNP types (spark-discharge and Printex90), with very similar physicochemical properties [≥98 and ≥95% elemental carbon; 10 and 14 nm primary particle diameter; and 800 and 300 m(2)/g specific surface area] for inhalation and IAI respectively. Mild pulmonary inflammatory responses and significant systemic effects were observed following 4 h and 24 h CNP inhalation. Increased retention of activated leukocytes, secondary thrombocytosis, and pro-inflammatory responses in secondary organs were detected following 4 h and 24 h of CNP inhalation only. Interestingly, among the investigated extra-pulmonary tissues (i.e. aorta, heart, and liver); aorta revealed as the most susceptible extra-pulmonary target following inhalation exposure. Bypassing the lungs by IAI however did not induce any extra-pulmonary effects at 4 h as compared to inhalation. Our findings indicate that extra-pulmonary effects due to CNP

  17. Salicylic acid analogues as chemical exchange saturation transfer MRI contrast agents for the assessment of brain perfusion territory and blood-brain barrier opening after intra-arterial infusion.

    Science.gov (United States)

    Song, Xiaolei; Walczak, Piotr; He, Xiaowei; Yang, Xing; Pearl, Monica; Bulte, Jeff Wm; Pomper, Martin G; McMahon, Michael T; Janowski, Mirosław

    2016-07-01

    The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. Predicted, focal opening of the BBB through intra-arterial infusion of hyperosmolar mannitol is feasible, but there is a need to facilitate imaging techniques (e.g. MRI) to guide interventional procedures and assess the outcomes. Here, we show that salicylic acid analogues (SAA) can depict the brain territory supplied by the catheter and detect the BBB opening, through chemical exchange saturation transfer (CEST) MRI. Hyperosmolar SAA solutions themselves are also capable of opening the BBB, and, when multiple SAA agents were co-injected, their locoregional perfusion could be differentiated.

  18. Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in very platinum-sensitive ovarian cancer patients

    DEFF Research Database (Denmark)

    Mahner, Sven; Meier, Werner; du Bois, Andreas;

    2015-01-01

    - and paclitaxel-based therapies. Patients were randomised to CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) and stratified by treatment-free interval (TFI). In this analysis, patients with a TFI>24 months were analysed separately for progression free survival (PFS...... (8% versus 3.1%; P=0.082) sensory neuropathy (4.8% versus 2.3%; P=0.27) and grade 2 alopecia (88% versus 9.2%; Pfoot syndrome occurred rarely with CD (3...

  19. Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma.

    Science.gov (United States)

    Kozicki, A R; Robat, C; Chun, R; Kurzman, I D

    2015-09-01

    Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti-tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post-operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease-free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment. © 2013 Blackwell Publishing Ltd.

  20. Hyperthermic isolated regional perfusion of the limb with carboplatin

    NARCIS (Netherlands)

    Daryanani, D; de Vries, EGE; Guchelaar, HJ; van Weerden, TW; Hoekstra, HJ

    2000-01-01

    Aims: To investigate the feasibility of hyperthermic isolated regional perfusion (HIRP) with carboplatin in the management of locally recurrent and/or intransit metastases of melanoma or locally advanced soft tissue sarcoma. Methods: Three patients, two with locally advanced melanoma and one with a

  1. PACLITAXEL PLUS CARBOPLATIN FOR WOMEN WITH ADVANCED BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    Ju Li; Qing Li; Pin Zhang; Jia-yu Wang; Long-mei Zhao; Bing-he Xu

    2007-01-01

    Objective To evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC).Methods From January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1,8, 15 every 4 weeks. Carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5.Results The median number of cycles was 3 (range, 2-6). The overall response rate was 62. 2%. Median time to progression was 7. 0 months (95%CI: 5. 1-8.9). Median overall survival was 29.0 months (95%CI: 20. 1-37.9). One year survival rate was 73. 3%. Response rate for first line and second line treatment were 62. 1 % and 62. 5% , respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade HI to IV adverse events included nausea/vomiting in 2 cases (4. 4% ), leukopenia in 17 cases (37. 8% ), and alopecia in 6 cases (13. 3% ).Conclusion Combination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

  2. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.

    Science.gov (United States)

    Mok, Tony S; Wu, Yi-Long; Thongprasert, Sumitra; Yang, Chih-Hsin; Chu, Da-Tong; Saijo, Nagahiro; Sunpaweravong, Patrapim; Han, Baohui; Margono, Benjamin; Ichinose, Yukito; Nishiwaki, Yutaka; Ohe, Yuichiro; Yang, Jin-Ji; Chewaskulyong, Busyamas; Jiang, Haiyi; Duffield, Emma L; Watkins, Claire L; Armour, Alison A; Fukuoka, Masahiro

    2009-09-03

    Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for

  3. Alterações histopatológicas associadas à braquiterapia intra-arterial com o samário-153

    Directory of Open Access Journals (Sweden)

    Précoma Dalton Bertolim

    2004-01-01

    Full Text Available A lesão da parede arterial provocada por balão de angioplastia ou implante de próteses endovasculares em modelos experimentais e humanos pode provocar a reestenose do vaso, principalmente por migração e proliferação de células musculares lisas e síntese de matriz extracelular. Vários estudos demonstraram que a braquiterapia intra-arterial atua nestes fatores e, conseqüentemente, no tratamento da reestenose coronariana. Este estudo tem por objetivo avaliar as alterações vasculares morfológicas e morfométricas induzidas pela braquiterapia com samário-153 (153Sm, utilizando uma dose considerada ideal e outra elevada em coelhos hipercolesterolêmicos. Foram analisados 43 coelhos hipercolesterolêmicos e um total de 86 artérias ilíacas submetidas à lesão por balão de angioplastia, divididos em três grupos, sendo irradiados com as doses de 15Gy (n = 14 e 60Gy (n = 36 e controle (n = 36. Foram realizadas análise morfométrica (área neo-intimal, área da camada média, área do vaso e análise histológica qualitativa para avaliação tecidual. O colesterol médio foi de 1.362 ± 497mg/dl nos três grupos. O achado mais relevante foi uma significativa inibição da hiperplasia neo-intimal no grupo irradiado com a dose de 15Gy, maior do que o controle e com a dose de 60Gy. Na dose de 60 Gy, além de ineficaz para inibir a proliferação neo-intimal, teve características tissulares e estruturais sugestivas de radiolesão, como presença de células xantomatosas, tecidos hialino e amorfo, proliferação vascular. Estas células, bem como o aumento das dimensões morfométricas do vaso, foram proporcionais aos graus de lesão nas lâminas elásticas interna e externa, sendo observados principalmente com a dose de 60Gy. Os segmentos médios das artérias ilíacas, representando o local de maior contato com o balão, tiveram maiores alterações morfométricas e celulares em relação aos segmentos referenciais (proximal e distal nos

  4. Carboplatin AUC 10 for IGCCCG good prognosis metastatic seminoma.

    Science.gov (United States)

    Tookman, Laura; Rashid, Sukaina; Matakidou, Athena; Phillips, Melissa; Wilson, Peter; Ansell, Wendy; Jamal-Hanjani, Mariam; Chowdhury, Simon; Harland, Stephen; Sarwar, Naveed; Oliver, Timothy; Powles, Thomas; Shamash, Jonathan

    2013-06-01

    Metastatic seminoma is a highly curable disease. Standard treatment comprises of combination chemotherapy. The short- and long-term toxicities of this treatment are increasingly recognised and the possibility of over treatment in such a curable disease should be considered. We have therefore assessed the use of single agent carboplatin at a dose of AUC 10 in patients with good prognosis metastatic seminoma. Patients with good prognosis metastatic seminoma treated with carboplatin (AUC 10) were identified at our institution and affiliated institutions. Treatment was three weekly for a total of three or four cycles. Outcome and toxicities were analysed. With a median follow-up of 36 months, 61 patients in total were treated with carboplatin AUC 10, all good prognosis by the IGCCCG criteria. Forty-eight percent had stage IIA/IIB disease and 52% had greater than stage IIB disease. Thirty-one patients (51%) had a complete response following treatment. Three-year survival was 96.3% with a three-year progression free survival of 93.2%. The main treatment toxicity was haematological with 46% having grade 3, 24% having grade 4 neutropenia and 54% experiencing grade 3/4 thrombocytopenia. There were no treatment related deaths. Single agent carboplatin at a dose of AUC 10 is an effective treatment for good prognosis metastatic seminoma. The outcome compares favourably to previously published outcomes of combination chemotherapy. Although haematological toxicity is a concern, single agent carboplatin treatment for good prognosis metastatic seminoma could be considered a treatment option and is associated with less toxicity than combination regimens currently used.

  5. Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Mikado, S. [Physical Science Laboratories, College of Industrial Technology, Nihon University, Chiba (Japan)], E-mail: mikado@cit.nihon-u.ac.jp; Yanagie, H. [Department of Nuclear Engineering and Management, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Yasuda, N. [Fundamental Technology Center, National Institute of Radiological Sciences, Chiba (Japan); Higashi, S.; Ikushima, I. [Miyakonojyo Metropolitan Hospital, Miyazaki (Japan); Mizumachi, R.; Murata, Y. [Department of Pharmacology, Kumamoto Institute Branch, Mitsubishi Chemical Safety Institute Ltd., Kumamoto (Japan); Morishita, Y. [Department of Human and Molecular Pathology, University of Tokyo, Tokyo (Japan); Nishimura, R. [Faculty of Agriculture, Laboratory of Veterinary Surgery, University of Tokyo (Japan); Shinohara, A. [Department of Humanities, The Graduate School of Seisen University, Tokyo (Japan); Ogura, K. [Physical Science Laboratories, College of Industrial Technology, Nihon University, Chiba (Japan); Sugiyama, H. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Iikura, H.; Ando, H. [Japan Atomic Energy Agency, Ibaraki (Japan); Ishimoto, M. [Department of Nuclear Professional School, University of Tokyo (Japan); Takamoto, S. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Cardiac Surgery, University of Tokyo Hospital, Tokyo (Japan); Eriguchi, M. [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Department of Microbiology, Syowa University School of Pharmaceutical Sciences, Tokyo (Japan); Takahashi, H. [Department of Nuclear Engineering and Management, University of Tokyo, Tokyo (Japan); Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kimura, M. [Department of Physics, Toho University, Chiba (Japan)

    2009-06-21

    It is necessary to accumulate the {sup 10}B atoms selectively to the tumor cells for effective Boron Neutron Capture Therapy (BNCT). In order to achieve an accurate measurement of {sup 10}B accumulations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of sliced samples of tumor tissues using CR-39 plastic track detectors. The CR-39 track detectors attached with the biological samples were exposed to thermal neutrons in the thermal column of the JRR3 of Japan Atomic Energy Agency (JAEA). We obtained quantitative NCAR images of the samples for VX-2 tumor in rabbit liver after injection of {sup 10}BSH entrapped water-in-oil-in-water (WOW) emulsion by intra-arterial injection via proper hepatic artery. The {sup 10}B accumulations and distributions in VX-2 tumor and normal liver of rabbit were investigated by means of alpha-track density measurements. In this study, we showed the selective accumulation of {sup 10}B atoms in the VX-2 tumor by intra-arterial injection of {sup 10}B entrapped WOW emulsion until 3 days after injection by using digitized NCAR images (i.e. alpha-track mapping)

  6. Segurança do transplante autólogo, intra-arterial, de células mononucleares da medula óssea na fase aguda do acidente vascular cerebral isquêmico Intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Maria Lúcia Furtado de Mendonça

    2006-01-01

    Full Text Available O acidente vascular cerebral (AVC é a terceira causa de óbito e a principal causa de incapacidade em indivíduos adultos. Embora a mortalidade do AVC esteja diminuindo em alguns países, a morbidade tem aumentado em razão do envelhecimento da população e do aumento da sobrevida dos pacientes¹. O tratamento com ativador do plasminogênio tissular recombinante (rt-PA é eficaz quando instituído em até 3 horas após o início dos sintomas², porém seu uso está limitado a cerca de 5% dos pacientes na fase aguda do AVC isquêmico. Além disso, nenhum agente para neuroproteção teve sua eficácia comprovada em estudos clínicos em humanos. Portanto, outras estratégias terapêuticas precisam ser desenvolvidas. Em modelos animais, o uso de células-tronco correlacionou-se com melhora funcional após o AVC³. Publicações recentes têm demonstrado a segurança do tratamento com células mononucleares da medula óssea (CMMO injetadas via intracoronária em pacientes portadores de cardiopatia isquêmica aguda ou crônica4,5. Baseado nesses dados iniciais, há crescente interesse no estudo do transplante com CMMO na fase aguda do AVC. Relatamos o primeiro caso de transplante autólogo de CMMO via intra-arterial na fase aguda do AVC isquêmico.Stroke is the third cause of death and the leading cause of disability in adult subjects. Although stroke mortality has been declining in some countries, stroke morbidity has been increasing due to the aging of population and patients improved survival.¹ Treatment with recombinant tissue plasminogen activator (rtPA is successful provided it is administered within 3 hours of symptoms onset,² but its use is limited to about 5% of the patients with acute ischemic stroke. Furthermore, no neuroprotective agent has yet been proven effective in human clinical trials. The development of other therapeutic strategies is, therefore, warranted. The use of stem cells in animal models has led to functional improvement

  7. 急性脑梗死动脉溶栓血管再通后的脑水肿研究%A clinical study on cerebral edema of intra-arterial thrombolytic recanalization in acute ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    马海; 任亚静; 张锡铎; 刘静; 郝锋利

    2013-01-01

    Objective To observe the cerebral edema occurrence ,evolution and prognosis of intra-arterial thrombolytic recanali-zation in patients with acute ischemic stroke .Methods From October 2010 to October 2012 ,36 patients who underwent the intra-arterial thrombolytic therapy were cerebral recanalization .They were randomly divided into two groups :1-3 h group and >3-6 h group .The alteration of brain edema was observed by cranial CT .Their mRS .NHISS and BI were scaled and recorded before and after intra-arterial thrombolytic therapy .Results After intra-arterial thrombolytic therapy ,the occurrence rate of cerebral edema was 94% ,appeared at the onset of more than 1 hours in all patients .Long-term follow-up showed ,cerebral edema location appeared obvious cerebromalacia .Cerebral edema and clinical outcome had not significant difference between 1-3 h group and 3-6 h group . Conclusion Cerebral edema and loss of cerebral tissue occurred almost inevitability in patients who received intra-artery thromboly-sis and recanalized their cerebral artery .It indicates that good local circulation and general condition may be favorable factors that can gradually reduce brain edema .%目的:观察急性缺血性脑卒中动脉溶栓血管再通后脑水肿的发生、演变及转归。方法2010年10月至2012年10月于该院就诊,通过动脉溶栓血管再通的患者共36例。将患者分为1~3 h组、>3~6 h组。头颅C T监测、随访脑水肿情况。记录溶栓前、术后1周及1年的美国国立卫生研究院卒中量表(NIHSS)、溶栓后1年改良蓝金评分(MRS)及巴塞尔指数(BI)。结果动脉溶栓血管再通后脑水肿的发生率为94%,出现在1~3 h组、>3~6 h组的所有患者中,长期随访表明,脑水肿局部出现了明显的软化灶。两组患者脑水肿及临床结局比较差异无统计学意义(P>0.05)。结论动脉溶栓血管再通后脑水肿的发生及其脑组织缺失几乎不可

  8. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumour with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Yanagie, Hironobu, E-mail: yanagie@n.t.u-tokyo.ac.jp [Dept of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)] [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kumada, Hiroaki [Proton Medical Research Center, University of Tsukuba, Ibaraki (Japan); Nakamura, Takemi [Japan Atomic Energy Research Institute, Ibaraki (Japan); Higashi, Syushi [Dept of Surgery, Ebihara Memorial Hospital, Miyazaki (Japan)] [Kyushu Industrial Sources Foundation, Miyazaki (Japan); Ikushima, Ichiro [Dept of Radiology, Miyakonojyo Metropolitan Hospital, Miyazaki (Japan); Morishita, Yasuyuki [Dept of Human and Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo (Japan); Shinohara, Atsuko [Dept of Humanities, Graduate School of Seisen University, Tokyo (Japan); Fijihara, Mitsuteru [SPG Techno Ltd. Co., Miyazaki (Japan); Suzuki, Minoru; Sakurai, Yoshinori [Research Reactor Institute, Kyoto University, Osaka (Japan); Sugiyama, Hirotaka [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan); Kajiyama, Tetsuya [Kyushu Industrial Sources Foundation, Miyazaki (Japan); Nishimura, Ryohei [Dept of Veternary Surgery, University of Tokyo Veternary Hospital, Tokyo (Japan); Ono, Koji [Research Reactor Institute, Kyoto University, Osaka (Japan); Nakajima, Jun; Ono, Minoru [Dept of Cardiothracic Surgery, University of Tokyo Hospital, Tokyo (Japan); Eriguchi, Masazumi [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)] [Department of Surgery, Shin-Yamanote Hospital, Saitama (Japan); Takahashi, Hiroyuki [Dept of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)] [Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, Tokyo (Japan)

    2011-12-15

    Introduction: Hepatocellular carcinoma (HCC) is one of the most difficult to cure with surgery, chemotherapy, or other combinational therapies. In the treatment of HCC, only 30% patients can be operated due to complication of liver cirrhosis or multiple intrahepatic tumours. Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between {sup 10}B atoms and thermal neutrons, so it is necessary to accumulate a sufficient quantity of {sup 10}B atoms in tumour cells for effective tumour cell destruction by BNCT. Water-in-oil-in-water (WOW) emulsion has been used as the carrier of anti-cancer agents on intra-arterial injections in clinical. In this study, we prepared {sup 10}BSH entrapped WOW emulsion by double emulsifying technique using iodized poppy-seed oil (IPSO), {sup 10}BSH and surfactant, for selective intra-arterial infusion to HCC, and performed simulations of the irradiation in order to calculate the dose delivered to the patients. Materials and methods: WOW emulsion was administrated with intra-arterial injections via proper hepatic artery on VX-2 rabbit hepatic tumour models. We simulated the irradiation of epithermal neutron and calculated the dose delivered to the tissues with JAEA computational dosimetry system (JCDS) at JRR4 reactor of Japan Atomic Research Institute, using the CT scans of a HCC patient. Results and discussions: The {sup 10}B concentrations in VX-2 tumour obtained by delivery with WOW emulsion were superior to those by conventional IPSO mix emulsion. According to the rabbit model, the boron concentrations (ppm) in tumour, normal liver tissue, and blood are 61.7, 4.3, and 0.1, respectively. The results of the simulations show that normal liver biologically weighted dose is restricted to 4.9 Gy-Eq (CBE; liver tumour: 2.5, normal liver: 0.94); the maximum, minimum, and mean tumour weighted dose are 43.1, 7.3, and 21.8 Gy-Eq, respectively, in 40 min irradiation. In this study, we show that {sup 10}B

  9. Efeitos cardiovasculares e renais da injeção intra-arterial de contraste radiológico iônico em cães com restrição hídrica Efectos cardiovasculares y renales de la inyección intra-arterial de contraste radiológico iónico en perros con restricción hídrica Cardiovascular and renal effects of intra-arterial injection of ionic radiological contrast in dogs under fluid restriction

    Directory of Open Access Journals (Sweden)

    Marisa Aparecida Lima Verderese

    2005-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O objetivo desta pesquisa foi estudar os efeitos agudos do contraste radiológico em situações de restrição de volume, avaliando-se os efeitos renais e cardiovasculares após a injeção intra-arterial de contraste radiológico de alta osmolaridade. MÉTODO: Participaram do estudo 16 cães anestesiados com tiopental sódico (15 mg.kg-1 e fentanil (15 µg.kg-1 em bolus, seguido de infusão contínua nas doses de 40 µg.kg-1.min-1 (tiopental sódico e 0,1 µg.kg-1.min-1 (fentanil. Foi feita hidratação com solução de glicose a 5% (0,03 mL.kg-1.min-1 e a ventilação pulmonar foi controlada mecanicamente com ar comprimido. Foram verificados os seguintes atributos: freqüência cardíaca (FC; pressão arterial média (PAM; pressão da veia cava inferior (PVI; débito cardíaco (DC; hematócrito (Ht; fluxo plasmático efetivo renal (FPER; fluxo sangüíneo renal (FSR; ritmo de filtração glomerular (RFG; fração de filtração; resistência vascular renal (RVR; volume urinário (VU; osmolaridade plasmática e urinária; depuração osmolar, depuração de água livre e depuração de sódio e de potássio; sódio e potássio plasmáticos; excreção urinária e fracionária de sódio e potássio e temperatura retal. Estes atributos foram avaliados em quatro momentos: 30 (M1, 60 (M2, 90 (M3 e 120 (M4 minutos após o início da infusão de para-aminohipurato de sódio e creatinina (início da experiência. No momento 2, no grupo G1 foi feita injeção intra-arterial de solução fisiológica a 0,9% (1,24 mL.kg-1, e no grupo G2 foi injetado contraste radiológico (1,24 mL.kg-1 pela mesma via. RESULTADOS: O grupo G1 apresentou aumento da FC, do FPER, do FSR, da osmolaridade plasmática, da depuração de sódio e da excreção urinária de sódio; apresentou ainda diminuição da osmolaridade urinária, do potássio plasmático, da depuração de potássio e da temperatura retal. No grupo G2 ocorreu aumento da FC, da

  10. Carboplatin: molecular mechanisms of action associated with chemoresistance

    Directory of Open Access Journals (Sweden)

    Graziele Fonseca de Sousa

    2014-12-01

    Full Text Available Carboplatin is a derivative of cisplatin; it has a similar mechanism of action, but differs in terms of structure and toxicity. It was approved by the FDA in the 1980s and since then it has been widely used in the treatment of several tumor types. This agent is characterized by its ability to generate lesions in DNA through the formation of adducts with platinum, thereby inhibiting replication and transcription and leading to cell death. However, its use can lead to serious inconvenience arising from the development of resistance that some patients acquire during treatment, limiting the scope of its full potential. Currently, the biochemical mechanisms related to resistance are not precisely known. Therefore, knowledge of pathways associated with resistance caused by carboplatin exposure may provide valuable clues for more efficient rational drug design in platinum-based therapy and the development of new therapeutic strategies. In this narrative review, we discuss some of the known mechanisms of resistance to platinum-based drugs, especially carboplatin.

  11. Study of intra-arterial interventional treatment in acute cerebral infarction%急性脑梗死患者动脉内介入治疗的临床体会

    Institute of Scientific and Technical Information of China (English)

    张海欣; 顾芳; 赵淑芹; 胡磊; 宋钦

    2012-01-01

    Objective To study the method and results of intra-arterial interventional treatment( selective intra-arterial fibrinolysis ) in acute cerebral infarction( ACI ). Methods 106 patients with ACI were divided into two groups: 53 cases in selective intra-arterial fibrinolytic therapy group( SIAF ) and intra-venously thrombolysis group ( IVF ); SIAF was selective entered into the obliterative artery with improved Seldingers techniche, pumped urokinase ( UK ) in a dose of 500,000 i. u. in NS. 60ml within 40 minutes; Arteriography was done all the time to know if the obliterative artery was unobstructed. If it remain obstmcte, then pumps 300,000i. u. of UK. The treatment was finished as long as it was unobstructed; IVF was injected 1000,000 i. u. of UK in NS. 150ml by intravenous drip within 40 minutes, others was same with SIAF. Results The artery was recanalization after thrombolysis, 44 patients in SIAF,33 patients in IVF,P <0. 05 ; the patients'condition was good,42 in SIAF,30 in IVF,P <0. 01; fatal cases,6 in SIAF, 12 in IVF,P < 0. 05. Conclusion Selective intra-arterial fibrinolysis is a effective method of treating ACI,the response to treatment is dramatic.%目的 研究急性脑梗死患者动脉内介入治疗(选择性动脉内溶栓)的方法 及疗效.方法 106例急性脑梗死患者,分为选择性动脉内溶栓组(SIAF组)、静脉溶栓组(IVF组)各53例;SIAF组采用改良Seldinger技术,选择性进入闭死的动脉,40分钟内泵入尿激酶50万单位+0.9%氯化钠60ml,随时做造影了解动脉通否,不通者再泵入尿激酶30万单位,只要闭死动脉再通,即撤除之.IVF组40分钟内静脉滴入尿激酶100万单位+0.9%氯化钠150ml,不通者再滴入尿激酶30万单位,余同上.结果 溶栓后再通者SIAF组44例,IVF组33例(P<0.05);病情好转者SIAF组42例,IVF组30例;SIAF组死亡6例,IVF组死亡12例(P<0.05).结论 急性脑梗死患者动脉内介入治疗,效果明显.

  12. A phase I study of bortezomib, etoposide and carboplatin in patients with advanced solid tumors refractory to standard therapy

    NARCIS (Netherlands)

    Lieu, Christopher; Chow, Laura; Pierson, A. Scott; Eckhardt, S. Gail; O'Bryant, Cindy L.; Morrow, Mark; Tran, Zung Vu; Wright, John J.; Gore, Lia

    2009-01-01

    Purpose: To evaluate the toxicity, pharmacological, and biological properties of the combination of bortezomib, etoposide, and carboplatin in adults with advanced solid malignancies. Patients and methods: Patients received escalating doses of bortezomib, etoposide, and carboplatin every 21 days. Sur

  13. 急性缺血性卒中动脉溶栓后造影剂渗出的临床分析%Clinical analysis on contrast extravasation after intra-arterial thrombolysis for acute ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    付睿; 贺茂林; 赵星辉; 黄栋; 席春江; 张彤; 戴威

    2013-01-01

    Objective To evaluate the risk factors and the prognosis for contrast extravasation after intraarterial(IA)thrombolysis for acute ischemic stroke.Methods A prospective and open-label trial was performed on 78 patients at the department of neurology in Beijing Shijitan Hospital from April 2008 to June 2012.Patients with acute ischemic stroke in the carotid artery system within 6 hours of symptom onset were treated with recombinant tissue plasminogen activator(rtPA) or urokinase (UK)by intra-artery thrombolysis approach.Arterial recanalization was assessed by the thrombolysis in cerebral infarction (TICI) classification.The functional outcome in 3-month was measured by mRS score.Contrast extravasation were observed by the baseline CT and postprocedure CTs.Results According to the results of digital subtraction angiography(DSA),30 patients had the internal carotid artery (ICA) occlusion and 48 patients had the middle cerebral artery(MCA) occlusion.The rote of recanalization after IA thrombolysis was 78.2% (61/78),the rate of contrast extravasation was 20.5% (16/78).Contrast extravasation were noted on immediate CT scans after intra-arterial thrombolysis in 4 patients with the ICA occlusion and 12 patients with the MCA occlusion.Patients with contrast extravasation had a partial or complete vascular recanalization.Favorable prognosis outcome,defined as a modified Rankin Score of 0-2 at 90 days,were significantly higher in patients without contrast extravasation than in patients with contrast extravasation(74.2% vs.43.8%) (P =0.020).The rate of symptomatic intracerebral hemorrhage (SICH)were significantly higher in patients with contrast extravasation than in patients without contrast extravasation(25% vs.3.2%)(P =0.017).Baseline NIHSS score >16 points (< 22 points),systolic pressure was more than 160 mm Hg during intra-arterial thrombolysis,vascular recanalization after intra-arterial thrombolysis,mechanical thrombus disruption by microcatheter and

  14. Efficacy of carboplatin-based preoperative chemotherapy for triple-negative breast cancer

    Science.gov (United States)

    Wang, Li-Yang; Xie, Hua; Zhou, Hang; Yao, Wen-Xiu; Zhao, Xin; Wang, Yi

    2017-01-01

    Objectives: To evaluate the efficacy and safety of carboplatin-based preoperative chemotherapy in triple-negative breast cancer patients (TNBC). Methods: PubMed, EMBASE, the Web of Science, the Cochrane Library, major clinical trial registries, and abstract collections from major international meetings were systematically searched for relevant randomized controlled trials. Endpoints included rates of pathologic complete response (pCR), overall response (ORR), breast-conserving surgery (BCS) and toxicity. Pooled relative risk (RR) was calculated for each endpoint using a fixed- or random-effect model depending on the heterogeneity among included studies. Results: A total of 5 randomized controlled trials involving 1007 patients were included in the meta-analysis. Carboplatin-based chemotherapy was associated with a pooled pCR rate of 53.3%, which was significantly higher than the rate associated with non-carboplatin therapy (37.8%, RR: 1.41, 95% confidence interval [CI]: 1.23 to 1.62, p<0.00001). Compared with non-carboplatin therapy (48.1%), carboplatin-based chemotherapy increased BCS rate (59.7%, RR: 1.24, 95% CI: 1.06 to 1.46, p=0.007). Carboplatin-based chemotherapy was associated with similar ORR as non-carboplatin therapy. Carboplatin-based chemotherapy was associated with higher incidence of grade 3 or 4 anemia, neutropenia, febrile neutropenia, and thrombocytopenia than non-carboplatin therapy, while the 2 regimens were associated with similar incidence of fatigue, leucopenia, and nausea/vomiting. Conclusion: The available evidence suggests that carboplatin-based preoperative chemotherapy is associated with significantly better pCR and BCS rates than non-carboplatin-based therapy in TNBC patients. PMID:28042625

  15. Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

    Science.gov (United States)

    Conte, P F; Bruzzone, M; Chiara, S; Rosso, R; Giaccone, G; Carnino, F; Guercio, E; Ragni, N; Foglia, G; Bentivoglio, G

    1988-04-30

    Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

  16. Carboplatin-Induced Bilateral Papilledema: A Case Report

    Directory of Open Access Journals (Sweden)

    N. Fischer

    2009-04-01

    Full Text Available We report on a patient with carboplatin-induced bilateral papilledema, as it was described in the 1970s for cisplatin. Loss of visual accuracy up to full blindness, often loss of color vision and scotomas can be seen as a result of cortical blindness, macula degeneration, retrobulbar neuritis and papilledema. These symptoms are mostly unilateral and initially mild, so that more chemotherapy is given before the diagnosis is made. The symptoms are usually reversible within weeks to months after cessation of the platinum treatment. The therapeutic strategy is stopping the platinum treatment. In addition the empiric use of corticosteroids is suggested.

  17. Basic Concurrency Theory

    DEFF Research Database (Denmark)

    Løvengreen, Hans Henrik

    2002-01-01

    In this set of notes, we present some of the basic theory underlying the discipline of programming with concurrent processes/threads. The notes are intended to supplement a standard textbook on concurrent programming.......In this set of notes, we present some of the basic theory underlying the discipline of programming with concurrent processes/threads. The notes are intended to supplement a standard textbook on concurrent programming....

  18. Concurrent weighted logic

    DEFF Research Database (Denmark)

    Xue, Bingtian; Larsen, Kim Guldstrand; Mardare, Radu Iulian

    2015-01-01

    We introduce Concurrent Weighted Logic (CWL), a multimodal logic for concurrent labeled weighted transition systems (LWSs). The synchronization of LWSs is described using dedicated functions that, in various concurrency paradigms, allow us to encode the compositionality of LWSs. To reflect these......-completeness results for this logic. To complete these proofs we involve advanced topological techniques from Model Theory....

  19. The Susceptibility Vessel Sign of the Middle Cerebral Artery on the T2-Weighted Gradient Echo Imaging: Semi-quantification to Predict the Response to Multimodal Intra-Arterial Thrombolysis

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Sung Won [Catholic University of Daegu Medical Center, Daegu (Korea, Republic of); Jung, Cheol Kyu; Choi, Byung Se; Kim, Jae Hyoung; Kwon, O Ki; Han, Moon Ku; Bae, Hee Joon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Kwon, Bae Ju [Kwandong University Myongji Hospital, Goyang (Korea, Republic of); Han, Moon Hee [Seoul National University Hospital, Seoul (Korea, Republic of)

    2011-01-15

    We wanted to determine whether or not the 'susceptibility asymmetry index' (SAI) of acute stroke on the T2-weighted image is related with successful recanalization using multimodal intra-arterial thrombolysis (IAT). The 81 patients who underwent multimodal IAT for middle cerebral artery (MCA) territory acute stroke were included in this retrospective study. The multimodal IAT included intra-arterial urokinase infusion, clot disruption by a microwire, microcatheter and balloon manipulation, and balloon angioplasty and/or stenting for the flow-limiting stenosis. The diameter of the susceptibility vessel sign was measured on the T2-weighted gradient echo imaging (GRE), and the diameter of the contralateral normal MCA at the corresponding level was measured on magnetic resonance angiography (MRA): the ratio between these two diameters was defined as the susceptibility asymmetry index. The relation between the TICI (Thrombolysis In Cerebral Infarction) score of 2-3 after multimodal IAT and the SAI was assessed. The receiver operating characteristic (ROC) curve analysis was performed on the SAI to predict a TICI score of 2-3 after multimodal IAT. The mean SAI of 81 patients was 1.66 {+-} 0.66. Seventy nine percent of the patients had a TICI of 2-3 after multimodal IAT. According to the ROC curve analysis, an SAI less than 1.3 was optimal for predicting the presence of stenotic lesion after recanalization (area under the curve: 0.821, sensitivity: 88.2%, specificity: 69.8%, p=0.0001), and the SAI {<=}1.61 (area under the curve: 0.652, sensitivity: 60.9%, specificity: 70.6%, p=0.0226) could predict a TICI score of 2-3. The TICI score of 2-3 after multimodal IAT was achieved in 88.6% of the cases with a SAI {<=} 1.61 and in 67.6% of the cases with a SAI >1.61 (p=0.028). The lower SAI on T2-GRE could predict stenotic lesion and successful recanalization after performing IAT

  20. Measuring and modelling concurrency

    Directory of Open Access Journals (Sweden)

    Larry Sawers

    2013-02-01

    Full Text Available This article explores three critical topics discussed in the recent debate over concurrency (overlapping sexual partnerships: measurement of the prevalence of concurrency, mathematical modelling of concurrency and HIV epidemic dynamics, and measuring the correlation between HIV and concurrency. The focus of the article is the concurrency hypothesis – the proposition that presumed high prevalence of concurrency explains sub-Saharan Africa's exceptionally high HIV prevalence. Recent surveys using improved questionnaire design show reported concurrency ranging from 0.8% to 7.6% in the region. Even after adjusting for plausible levels of reporting errors, appropriately parameterized sexual network models of HIV epidemics do not generate sustainable epidemic trajectories (avoid epidemic extinction at levels of concurrency found in recent surveys in sub-Saharan Africa. Efforts to support the concurrency hypothesis with a statistical correlation between HIV incidence and concurrency prevalence are not yet successful. Two decades of efforts to find evidence in support of the concurrency hypothesis have failed to build a convincing case.

  1. Constraints meet concurrency

    CERN Document Server

    Mauro, Jacopo

    2014-01-01

    This book describes the benefits that emerge when the fields of constraint programming and concurrency meet. On the one hand, constraints can be used in concurrency theory to increase the conciseness and the expressive power of concurrent languages from a pragmatic point of view. On the other hand, problems modeled by using constraints can be solved faster and more efficiently using a concurrent system. Both directions are explored providing two separate lines of development. Firstly the expressive power of a concurrent language is studied, namely Constraint Handling Rules, that supports constraints as a primitive construct. The features of this language which make it Turing powerful are shown. Then a framework is proposed to solve constraint problems that is intended to be deployed on a concurrent system. For the development of this framework the concurrent language Jolie following the Service Oriented paradigm is used. Based on this experience, an extension to Service Oriented Languages is also proposed in ...

  2. Whole-genome approach implicates CD44 in cellular resistance to carboplatin

    Directory of Open Access Journals (Sweden)

    Shukla Sunita J

    2009-01-01

    Full Text Available Abstract Carboplatin is a chemotherapeutic agent used in the management of many cancers, yet treatment is limited by resistance and toxicities. To achieve a better understanding of the genetic contribution to carboplatin resistance or toxicities, lymphoblastoid cell lines from 34 large Centre d'Etude du Polymorphisme Humain pedigrees were utilised to evaluate interindividual variation in carboplatin cytotoxicity. Significant heritability, ranging from 0.17-0.36 (p = 1 × 10-7 to 9 × 10-4, was found for cell growth inhibition following 72-hour treatment at each carboplatin concentration (10, 20, 40 and 80 μM and IC50 (concentration for 50 per cent cell growth inhibition. Linkage analysis revealed 11 regions with logarithm of odds (LOD scores greater than 1.5. The highest LOD score on chromosome 11 (LOD = 3.36, p = 4.2 × 10-5 encompasses 65 genes within the 1 LOD confidence interval for the carboplatin IC50. We further analysed the IC50 phenotype with a linkage-directed association analysis using 71 unrelated HapMap and Perlegen cell lines and identified 18 single nucleotide polymorphisms within eight genes that were significantly associated with the carboplatin IC50 (p -5; false discovery rate 50 values of the eight associated genes, which identified the most significant correlation between CD44 expression and IC50 (r2 = 0.20; p = 6 × 10-4. The quantitative real-time polymerase chain reaction further confirmed a statistically significant difference in CD44 expression levels between carboplatin-resistant and -sensitive cell lines (p = 5.9 × 10-3. Knockdown of CD44 expression through small interfering RNA resulted in increased cellular sensitivity to carboplatin (p CD44 as being important in conferring cellular resistance to carboplatin.

  3. Advanced thymic cancer treated with carboplatin and paclitaxel in a patient undergoing hemodialysis.

    Science.gov (United States)

    Miura, Satoru; Kagamu, Hiroshi; Sakai, Takehito; Nozaki, Koichiro; Asakawa, Katsuaki; Moro, Hiroshi; Okajima, Masaaki; Watanabe, Satoshi; Yamamoto, Suguru; Iino, Noriaki; Goto, Shin; Kazama, Junichiro James; Yoshizawa, Hirohisa; Narita, Ichiei

    2015-01-01

    A 53-year-old man with an asymptomatic anterior mediastinal tumor undergoing hemodialysis was referred to our institution. He was diagnosed with thymic basaloid carcinoma based on the findings of a chest tomography-guided biopsy and successfully treated with carboplatin (300 mg/m(2)/day) and paclitaxel (200 mg/m(2)/day) on day 1 for six three-week cycles. To our knowledge, this is the first report regarding the efficiency of a carboplatin dose-definition method based on the body surface area with paclitaxel in a hemodialysis patient. This report may therefore be useful for treating hemodialysis patients who are candidates for carboplatin and paclitaxel therapy.

  4. Towards Composable Concurrency Abstractions

    Directory of Open Access Journals (Sweden)

    Janwillem Swalens

    2014-06-01

    Full Text Available In the past decades, many different programming models for managing concurrency in applications have been proposed, such as the actor model, Communicating Sequential Processes, and Software Transactional Memory. The ubiquity of multi-core processors has made harnessing concurrency even more important. We observe that modern languages, such as Scala, Clojure, or F#, provide not one, but multiple concurrency models that help developers manage concurrency. Large end-user applications are rarely built using just a single concurrency model. Programmers need to manage a responsive UI, deal with file or network I/O, asynchronous workflows, and shared resources. Different concurrency models facilitate different requirements. This raises the issue of how these concurrency models interact, and whether they are composable. After all, combining different concurrency models may lead to subtle bugs or inconsistencies. In this paper, we perform an in-depth study of the concurrency abstractions provided by the Clojure language. We study all pairwise combinations of the abstractions, noting which ones compose without issues, and which do not. We make an attempt to abstract from the specifics of Clojure, identifying the general properties of concurrency models that facilitate or hinder composition.

  5. Clinical result of intra-arterial lymphocyte injection therapy for treatment of lymphedema and the evaluation of the efficacy of the therapy. Quantitative analysis by an injection of {sup 111}In-labeled lymphocytes and by MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizumi, Masanori; Kitagawa, Tetsuya; Hori, Takaki; Katoh, Itsuo; Harada, Masashi; Matsumoto, Takahiro; Nishitani, Hiromu [Tokushima Univ. (Japan). School of Medicine

    1995-11-01

    We have employed the intra-arterial lymphocytes injection therapy for treatment of lymphedema of the limbs with various causes. In the present study, we observed the clinical outcome of our therapy in 38 patients with lymphedema of the limbs. Results showed that the therapy was effective in 26 of 38 patients (68% of the total). Moreover, a marked efficacy was obtained in 13 of 38 patients (34% of the total). In the latest 5 patients, to evaluate the efficacy of our therapy, we examined the distribution of the {sup 111}In-oxine labeled lymphocytes injected into the proximal artery of the affected limb. The radioactivities of the affected limbs were apparently higher than that of the healthy limbs in effective cases. Moreover, MR imaging showed that the reduction of STIR ratio and T{sub 2} ratio well correlate with the results of clinical course. Thus, the efficacy of the lymphocyte injection therapy is able to be evaluated by radiolabeled lymphocytes and MR imaging. (author).

  6. Embolização intra-arterial pré-operatória de tumor do corpo carotídeo Preoperative intraarterial embolization of carotid body tumor

    Directory of Open Access Journals (Sweden)

    Gaudêncio Espinosa

    2006-09-01

    Full Text Available Os autores relatam um caso de tumor de corpo carotídeo (paraganglioma em um paciente de 74 anos de idade, submetido a embolização intra-arterial com micropartículas esféricas, de polivinil acetato, com casca de polivinil álcool (PVAc + PVA, previamente à ressecção do tumor. O estudo angiográfico demonstrou massa altamente vascularizada na bifurcação carotídea esquerda, sendo a embolização pré-operatória utilizada no intuito de diminuir a vascularização e reduzir a perda sangüínea, aumentando a segurança do tratamento cirúrgico. O estudo histopatológico confirmou a presença de trombose e isquemia tecidual.The authors report a case of carotid body tumor (paraganglioma in a 74-year-old male patient, submitted to intraarterial embolization with spherical core/shield polyvinyl acetate and polyvinyl alcohol (PVAc + PVA microparticles prior to surgical excision. Angiography has demonstrated a highly vascularized mass in the left carotid bifurcation, and preoperative embolization was used in order to decrease vascularity, reduce blood loss and improve safety of surgical treatment. Microscopic study confirmed presence of thrombosis and tissue ischemia.

  7. Subtenon Carboplatin in the Management of Intraocular Retinoblastoma

    Directory of Open Access Journals (Sweden)

    Reza Karkhaneh

    2008-12-01

    Full Text Available

    PURPOSE: To evaluate the efficacy of adjuvant subtenon carboplatin in the management of intraocular retinoblastoma. METHODS: This study was conducted as a randomized, double-masked clinical trial. A diagnosis of intraocular retinoblastoma was made based on clinical examination, ultrasonography and orbital CT-scanning. The greatest basal dimension of the tumors was estimated in disc diameter (DD by indirect ophthalmoscopy. Tumor thickness was determined by ultrasonography. Each eye was assigned to one of 10 blocks based on tumor stage (Reese-Ellsworth classification and randomly received systemic chemotherapy alone (control group or systemic chemotherapy plus 20mg subtenon carboplatin (case group. Indirect laser photocoagulation or cryotherapy was performed as additional treatment. RESULTS: The study included 35 tumors in 17 eyes of 14 patients (19 tumors in 8 eyes in the control group and 16 tumors in 9 eyes in the case group. There was 57.22% and 61.73% decrease in tumor thickness in the control and case groups, respectively. This difference was not statistically significant (P=0.12. The decrease in greatest basal tumor dimension in the control group (47.32% was not significantly different from that in the case group (38.80%. One eye (12.5% in the control group and 3 eyes (33.3% in the case group were enucleated. CONCLUSION

  8. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Valencia Posso, Frank Dan

    2002-01-01

    The ntcc calculus is a model of non-deterministic temporal concurrent constraint programming. In this paper we study behavioral notions for this calculus. In the underlying computational model, concurrent constraint processes are executed in discrete time intervals. The behavioral notions studied...... reflect the reactive interactions between concurrent constraint processes and their environment, as well as internal interactions between individual processes. Relationships between the suggested notions are studied, and they are all proved to be decidable for a substantial fragment of the calculus...

  9. Separation Logic and Concurrency

    Science.gov (United States)

    Bornat, Richard

    Concurrent separation logic is a development of Hoare logic adapted to deal with pointers and concurrency. Since its inception, it has been enhanced with a treatment of permissions to enable sharing of data between threads, and a treatment of variables as resource alongside heap cells as resource. An introduction to the logic is given with several examples of proofs, culminating in a treatment of Simpson's 4-slot algorithm, an instance of racy non-blocking concurrency.

  10. 77 FR 35985 - Determination That PARAPLATIN (Carboplatin) Injection and SUSTIVA (Efavirenz) Capsules Were Not...

    Science.gov (United States)

    2012-06-15

    ... SUSTIVA (Efavirenz) Capsules Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY... (efavirenz) Capsule, 100 Bristol Myers Squibb. milligrams (mg). NDA 20-452 PARAPLATIN (carboplatin) Do...

  11. Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers

    Science.gov (United States)

    Moisan, Francois; Francisco, Edgar B.; Brozovic, Anamaria; Duran, George E.; Wang, Yan C.; Chaturvedi, Shalini; Seetharam, Shobha; Snyder, Linda A.; Doshi, Parul; Sikic, Branimir I.

    2016-01-01

    Ovarian cancer is associated with a leukocyte infiltrate and high levels of chemokines such as CCL2. We tested the hypothesis that CCL2 inhibition can enhance chemotherapy with carboplatin and paclitaxel. Elevated CCL2 expression was found in three non-MDR paclitaxel resistant ovarian cancer lines ES-2/TP, MES-OV/TP and OVCAR-3/TP, compared to parental cells. Mice xenografted with these cells were treated with the anti-human CCL2 antibody CNTO 888 and the anti-mouse MCP-1 antibody C1142, with and without paclitaxel or carboplatin. Our results show an additive effect of CCL2 blockade on the efficacy of paclitaxel and carboplatin. This therapeutic effect was largely due to inhibition of mouse stromal CCL2. We show that inhibition of CCL2 can enhance paclitaxel and carboplatin therapy of ovarian cancer. PMID:24816187

  12. Elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro.

    Science.gov (United States)

    Tulipan, Rachel J; Phillips, Heidi; Garrett, Laura D; Dirikolu, Levent; Mitchell, Mark A

    2016-11-01

    OBJECTIVE To characterize the elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CSH) beads in vitro. SAMPLE 60 carboplatin-impregnated CSH beads and 9 CSH beads without added carboplatin (controls). PROCEDURES Carboplatin-impregnated CSH beads (each containing 4.6 mg of carboplatin [2.4 mg of platinum]) were placed into separate 10-mL plastic tubes containing 5 mL of PBSS in groups of 1, 3, 6, or 10; 3 control beads were placed into a single tube of PBSS at the same volume. Experiments were conducted in triplicate at 37°C and a pH of 7.4 with constant agitation. Eluent samples were collected at 1, 2, 3, 6, 12, 24, and 72 hours. Samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS The mean concentration of platinum released per carboplatin-impregnated bead over 72 hours was 445.3 mg/L. Cumulative concentrations of platinum eluted increased as the number of beads per tube increased. There was a significant difference in platinum concentrations over time, with values increasing over the first 12 hours and then declining for all tubes. There was also a significant difference in percentage of total incorporated platinum released into tubes with different numbers of beads: the percentage of eluted platinum was higher in tubes containing 1 or 3 beads than in those containing 6 or 10 beads. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated CSH beads eluted platinum over 72 hours. Further studies are needed to determine whether implantation of carboplatin-impregnated CSH beads results in detectable levels of platinum systemically and whether the platinum concentrations eluted locally are toxic to tumor cells.

  13. Concurrent Software Engineering Project

    Science.gov (United States)

    Stankovic, Nenad; Tillo, Tammam

    2009-01-01

    Concurrent engineering or overlapping activities is a business strategy for schedule compression on large development projects. Design parameters and tasks from every aspect of a product's development process and their interdependencies are overlapped and worked on in parallel. Concurrent engineering suffers from negative effects such as excessive…

  14. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Palamidessi, Catuscia; Valencia, Frank Dan

    2002-01-01

    The ntcc calculus is a model of non-deterministic temporal concurrent constraint programming. In this paper we study behavioral notions for this calculus. In the underlying computational model, concurrent constraint processes are executed in discrete time intervals. The behavioral notions studied...

  15. Concurrent Software Engineering Project

    Science.gov (United States)

    Stankovic, Nenad; Tillo, Tammam

    2009-01-01

    Concurrent engineering or overlapping activities is a business strategy for schedule compression on large development projects. Design parameters and tasks from every aspect of a product's development process and their interdependencies are overlapped and worked on in parallel. Concurrent engineering suffers from negative effects such as excessive…

  16. Probabilistic Concurrent Kleene Algebra

    Directory of Open Access Journals (Sweden)

    Annabelle McIver

    2013-06-01

    Full Text Available We provide an extension of concurrent Kleene algebras to account for probabilistic properties. The algebra yields a unified framework containing nondeterminism, concurrency and probability and is sound with respect to the set of probabilistic automata modulo probabilistic simulation. We use the resulting algebra to generalise the algebraic formulation of a variant of Jones' rely/guarantee calculus.

  17. Impredicative concurrent abstract predicates

    DEFF Research Database (Denmark)

    Svendsen, Kasper; Birkedal, Lars

    2014-01-01

    We present impredicative concurrent abstract predicates { iCAP { a program logic for modular reasoning about concurrent, higher- order, reentrant, imperative code. Building on earlier work, iCAP uses protocols to reason about shared mutable state. A key novel feature of iCAP is the ability to dene...

  18. Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

    Science.gov (United States)

    Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

    1998-06-01

    Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain

  19. Intra-arterial administration of tumor-targeting Salmonella typhimurium A1-R regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model.

    Science.gov (United States)

    Igarashi, Kentaro; Kawaguchi, Kei; Murakami, Takashi; Kiyuna, Tasuku; Miyake, Kentaro; Nelson, Scott D; Dry, Sarah M; Li, Yunfeng; Yanagawa, Jane; Russell, Tara A; Singh, Arun S; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Eilber, Fritz C; Hoffman, Robert M

    2017-06-18

    Previously, a patient-derived orthotopic xenograft (PDOX) model was established with a lung metastasis from an osteosarcoma patient which developed after adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared with CDDP. In the present report, osteosarcoma tissue was implanted orthotopically in the distal femur of mice which were randomized into the following groups when tumor volume reached approximately 100 mm(3); On day 14 after initiation of treatment, all but CDDP significantly inhibited tumor volume growth compared with untreated controls. Control (G1): 793.7 ± 215.0 mm(3); CDDP (G2): 588.1 ± 176.9 mm(3); Salmonella typhimurium A1-R (S. typhimurium A1-R) intravenous (i.v.) (G3): 269.7 ± 72.7 mm(3); S. typhimurium A1-R intra-arterial (i.a.) (G4): 70.2 ± 18.9 mm(3) (CDDP: p = 0.056; S. typhimurium A1-R i.v.: p = 0.0001; S. typhimurium A1-R i.a.: p = 0.00003, all vs. untreated controls). i.a. administration of S. typhimurium A1-R was significantly more effective than either CDDP (p = 0.00007), or i.v. administration of S. typhimurium A1-R (p = 0.00007) and significantly regressed the tumor volume compared with day 0 (p = 0.001). The new model of i.a. administration of S. typhimurium A1-R has great promise for the treatment of recalcitrant osteosarcoma.

  20. Comparison of 111In-[DTPA0]Octreotide Versus Non Carrier Added 177Lu- [DOTA0,Tyr3]-Octreotate Efficacy in Patients With GEP-NET Treated Intra-arterially for Liver Metastases.

    Science.gov (United States)

    Limouris, G S; Poulantzas, V; Trompoukis, N; Karfis, I; Chondrogiannis, S; Triantafyllou, N; Gennimata, V; Moulopoulou, L-E; Patsouris, E; Nikou, G; Michalaki, V; Fragulidis, G; Paphiti, M; McCready, R V; Colletti, P M; Cook, G J; Rubello, D

    2016-03-01

    In patients with progressive, metastatic neuroendocrine tumors (NET), intra-arterial radionuclide infusions with high activities of In-[DTPA]-octreotide and more recently with non-carrier added (nca) Lu-[DOTA,Tyr]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (In-[DTPA]-octreotide, 22 ± 3.6 nM and nca Lu-[DOTA,Tyr]-octreotate, 1.5 ± 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs. Thirty patients with gastroenteropancreatic (GEP) somatostatin-positive NETs with liver metastases confirmed on biopsy and In-pentetreotide scan were included. They were treated with In-[DTPA]-octreotide (n = 17) or nca Lu-[DOTA,Tyr]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/ 1.0 software. ncaLu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than In-[DTPA]-octreotide (P DTPA]-octreotide but without any significant difference in other organs (spleen, kidneys, and liver). Using Lu-[DOTA,Tyr]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with In-[DTPA] octreotide. Residence time of nca Lu-[DOTA,Tyr]-octreotate results in a significantly higher absorbed dose to bone marrow compared with In-[DTPA]-octreotide. However, a drawback of In-[DTPA]-octreotide therapy is that the number of administrations would need to be almost doubled to achieve an equal therapeutic outcome as compared with Lu-[DOTA,Tyr]-octreotate.

  1. [(111)In-DTPA]octreotide tumor uptake in GEPNET liver metastases after intra-arterial administration: an overview of preclinical and clinical observations and implications for tumor radiation dose after peptide radionuclide therapy.

    Science.gov (United States)

    Pool, Stefan E; Kam, Boen L R; Koning, Gerben A; Konijnenberg, Mark; Ten Hagen, Timo L M; Breeman, Woulter A P; Krenning, Eric P; de Jong, Marion; van Eijck, Casper H J

    2014-05-01

    With the aim to improve peptide receptor radionuclide therapy effects in patients with gastroenteropancreatic neuroendocrine tumor (GEPNET) liver metastases we explored the effect of intra-arterial (IA) administration of [(111)In-DTPA]octreotide ((111)In-DTPAOC) on tumor uptake in an animal model and in a patient study. Preclinical study: After administering (111)In-DTPAOC intra-venously (IV) or IA, biodistribution studies were performed in rats with a hepatic somatostatin receptor subtype 2 (sst2)-positive tumor. Clinical study: 3 patients with neuroendocrine liver metastases were injected twice with (111)In-DTPAOC. The first injection was given IV, and 2 weeks later, the second was injected IA (hepatic artery). Planar images of the abdomen were made up to 72 hours after injection. Blood samples were taken and urine was collected. Pharmacokinetic modeling was performed on the IV and IA data of the same patient. Based on this model, additional (177)Lu dosimetry calculations for IV and IA administrations were performed. The preclinical study showed a two-fold higher (111)In-DTPAOC tumor uptake after IA administration than after IV injection. Patient data showed a large variability in radioactivity increment in liver metastases after IA administration compared with IV administration. Renal radioactivity was not significantly lower after IA administration; (177)Lu dosimetry simulations in 1 patient using a maximum kidney radiation dose of 23 Gy showed IA administration resulted in a mean increase in tumor radiation dose of 2.9-fold. Preclinical and clinical data both indicate that IA administration of radiolabeled somatostatin analogs via the hepatic artery can significantly increase radionuclide uptake in GEPNET, sst2-positive, liver metastases up to 72 hours postinjection, although the effect of IA administration can differ between patients.

  2. Safe and easy method with little modification in technique is useful for successful internal jugular vein cannulation on the same side even after intra-arterial puncture without using ultrasound guidance in adult cardiac patients

    Directory of Open Access Journals (Sweden)

    Rajesh Thosani

    2016-01-01

    Full Text Available Background: The modification in technique is useful for successful right-sided internal jugular vein (IJV cannulation on the same side even after intra-arterial puncture without using ultrasound guidance in adult patients. Materials and Methods: This study was carried out in total 160 adult patient from American Society of Anesthesiologists Grade II to III patients male (n = 95 and female (n = 65 who underwent cardiac surgery where cannulation was done on right sided by triple lumen catheter (7 French using Seldinger technique. Results: Majority of patients were cannulated successfully by Seldinger technique with single or double attempt except for five patients in which arterial puncture occurred. All five patients were cannulated successfully on the same side with this modified technique without any significant major complications. They were managed by application of blocker at the end of arterial needle puncture without removing it. In our routine practice, we were used to removing this needle and applying compression for few minutes to prevent hematoma formation after an arterial puncture. In this study, cannula was used as a marker or guideline for the relocation of IJV on the same side and recannulation was performed by changing the direction of needle on same side lateral to the previous one and without going towards the same direction to prevent the arterial puncture again. Conclusion: Most simple and useful modified technique for institutes where the complications are most common with trainee doctors and in hospitals where there is no advanced facility like ultrasound-guided cannulation available. By this modification, it will be time saving, very comfortable, and user-friendly technique with high success rate.

  3. Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands).

    Science.gov (United States)

    Mulder, Maxim J H L; Ergezen, Saliha; Lingsma, Hester F; Berkhemer, Olvert A; Fransen, Puck S S; Beumer, Debbie; van den Berg, Lucie A; Lycklama À Nijeholt, Geert; Emmer, Bart J; van der Worp, H Bart; Nederkoorn, Paul J; Roos, Yvo B W E M; van Oostenbrugge, Robert J; van Zwam, Wim H; Majoie, Charles B L M; van der Lugt, Aad; Dippel, Diederik W J

    2017-07-01

    High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT. This is a post hoc analysis of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). BP was measured at baseline, before IAT or stroke unit admission. We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis. Effect of BP on the effect of IAT was tested with multiplicative interaction terms. Systolic BP (SBP) had the best correlation with functional outcome. This correlation was U-shaped; both low and high baseline SBP were associated with poor functional outcome. Higher SBP was associated with symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg higher SBP [95% confidence interval, 1.09-1.44]). Between SBP and IAT, there was no interaction for functional outcome, symptomatic intracranial hemorrhage, or other safety parameters; the absolute benefit of IAT was evident for the whole SBP range. The same was found for diastolic BP. BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion. Our data provide no arguments to withhold or delay IAT based on BP. URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

  4. Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    relation over two objects and an event. In the model, objects can be composed by parallel composition, encapsulation, and hiding of operations. Refinement between objects is defined as fair trace inclusion.A specification language is presented where objects can be specified operationally by abstract......Concurrent objects are named concurrent processes that interact by invoking each other's operations. We describe how such concurrent objects can be specified, how objects can be composed, and how it can be shown that one object refines another.First a model is defined, based on a transition...

  5. Transcatheter Arterial Embolization of Renal VX-2 Carcinoma: Ethiodol-Ethanol Capillary Embolization Combined with Carboplatin

    Energy Technology Data Exchange (ETDEWEB)

    Konya, Andras; Pelt, Carolyn S. Van; Wright, Kenneth C. [The University of Texas MD Anderson Cancer Center, Hoston (United States); Choi, Byung Gil [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-04-15

    We wanted to determine whether transcatheter Ethiodol-based capillary embolization in combination with carboplatin could improve the efficiency of a 1:1 Ethiodol-ethanol mixture (EEM) to ablate kidneys that been inoculated with VX-2 carcinoma. The right kidney in 34 New Zealand white rabbits were inoculated with fresh VX-2 tumor fragments. One week later, the kidneys were subjected to transarterial treatment (4-5 rabbits/group): Saline infusion (Group 1); carboplatin infusion (5 or 10 mg, Groups 2A and 2B); carboplatin- Ethiodol (CE) alone (Group 3) and followed by main renal artery occlusion with ethanol (RAO) (Group 4); carboplatin-EEM (C-EEM) followed by RAO (Group 5); carboplatin infusion followed by EEM plus RAO (Group 6); and EEM followed by RAO (Group 7). The animals were followed for up to 3-weeks. The treated kidneys were evaluated angiographically and macroscopically. The kidneys that showed successful embolization macroscopically were entirely cut into serial sections, and these were examined microscopically. Histologically, the kidneys were evaluated on the basis of the residual tumor found in the serial sections. The results obtained with carboplatin infusion alone (Groups 2A and 2B) and CE without RAO (Group 3) were similar to those of the control animals (Group 1). Kidneys from Groups 4-7 demonstrated macroscopically successful embolization with histologically proven complete renal parenchyma infarction; however, some residual tumor was evident in all but one animal. None of the Ethiodol-based modalities combined with locoregional carboplatin were more efficacious for tumor ablation than EEM alone.

  6. Building Safe Concurrency Abstractions

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    2014-01-01

    Concurrent object-oriented programming in Beta is based on semaphores and coroutines and the ability to define high-level concurrency abstractions like monitors, and rendezvous-based communication, and their associated schedulers. The coroutine mechanism of SIMULA has been generalized...... into the notions of concurrent and alternating objects. Alternating objects may be used to start a cooperative thread for each possible blocking communication and is thus an alternative to asynchronous messages and guarded commands. Beta like SIMULA, the first OO language, was designed as a language for modeling...... as well as programming, and we describe how this has had an impact on the design of the language. Although Beta supports the definition of high-level concurrency abstractions, the use of these rely on the discipline of the programmer as is the case for Java and other mainstream OO languages. We introduce...

  7. Concurrent bisimulation algorithm

    OpenAIRE

    Kułakowski, Konrad

    2013-01-01

    The coarsest bisimulation-finding problem plays an important role in the formal analysis of concurrent systems. For example, solving this problem allows the behavior of different processes to be compared or specifications to be verified. Hence, in this paper an efficient concurrent bisimulation algorithm is presented. It is based on the sequential Paige and Tarjan algorithm and the concept of the state signatures. The original solution follows Hopcroft's principle "process the smaller half". ...

  8. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel : NVALT-3 a phase III study

    NARCIS (Netherlands)

    Biesma, B.; Wymenga, A. N. M.; Vincent, A.; Dalesio, O.; Smit, H. J. M.; Stigt, J. A.; Smit, E. F.; van Felius, C. L.; van Putten, J. W. G.; Slaets, J. P. J.; Groen, H. J. M.

    Patients and methods: A total of 181 chemotherapy-naive patients [>= 70 years, performance score (PS) of 0-2] with stage III-IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Primary end point was change in

  9. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Science.gov (United States)

    Wang, Zhi-Yong; Zhang, Jun-Ai; Wu, Xian-Jin; Liang, Yan-Fang; Lu, Yuan-Bin; Gao, Yu-Chi; Dai, You-Chao; Yu, Shi-Yan; Jia, Yan; Fu, Xiao-Xia; Rao, Xiaoquan; Xu, Jun-Fa

    2016-01-01

    Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents. PMID:27006530

  10. Time-frequency analysis of transient-evoked otoacoustic emissions in children exposed to carboplatin chemotherapy.

    Science.gov (United States)

    Bhagat, Shaum; Bass, Johnnie; Qaddoumi, Ibrahim; Brennan, Rachel; Wilson, Matthew; Wu, Jianrong; Galindo, Carlos-Rodriguez; Paglialonga, Alessia; Tognola, Gabriella

    2013-01-01

    The aims of this study were to characterize and quantify time-frequency changes in transient-evoked otoacoustic emissions (TEOAEs) recorded in children diagnosed with retinoblastoma who were receiving carboplatin chemotherapy. A signal processing technique, the wavelet transform (WT), was used to analyze TEOAE waveforms in narrow-band frequency components. Ten children (aged 3-72 months) diagnosed with unilateral or bilateral retinoblastoma were enrolled in the study. TEOAEs were acquired from the children with linear sequences of 70 dB peak equivalent SPL clicks. After WT analysis, TEOAE energy, latency and normalized energy in the narrow-band frequency components were compared before and during carboplatin chemotherapy treatment (average dose 1693 mg/m2). On a group basis, no significant differences (p>0.05) in the TEOAE energy, latency or normalized energy before and after carboplatin treatment were observed. There were decreases in normalized energy on an individual basis in 10 out of 18 ears in the sample. Exposure to carboplatin chemotherapy did not cause significant changes in TEOAE energy, latency and normalized energy during treatment. However, long-term monitoring of hearing with measurements of TEOAEs is warranted, given the risks of delayed hearing loss in some children receiving carboplatin chemotherapy.

  11. Methylseleninic acid sensitizes Notch3-activated OVCA429 ovarian cancer cells to carboplatin.

    Directory of Open Access Journals (Sweden)

    Tiffany J Tzeng

    Full Text Available Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3 is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3 in OVCA429 ovarian cancer cells (OVCA429/NICD3 renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein kinase in cancer cells. Here we tested the hypothesis that MSeA and carboplatin exerted a synthetic lethal effect on OVCA429/NICD3 cells. Co-treatment with MSeA synergistically sensitized OVCA429/NICD3 but not OVCA429/pCEG cells to the killing by carboplatin. This synergism was associated with a cell cycle exit at the G2/M phase and the induction of NICD3 target gene HES1. Treatment of N-acetyl cysteine or inhibitors of the above two kinases did not directly impact on the synergism in OVCA429/NICD3 cells. Taken together, these results suggest that the efficacy of carboplatin in the treatment of high grade ovarian carcinoma can be enhanced by a combinational therapy with MSeA.

  12. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Wang

    2016-01-01

    Full Text Available Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

  13. Regional intra-arterial chemotherapy for treatment of advanced malignant tumors in children%小儿不可切除性恶性实体瘤区域性动脉化疗的探讨

    Institute of Scientific and Technical Information of China (English)

    李民驹; 黄勇; 吴德华; 唐达星; 徐珊; 周银宝; 章毅英

    2009-01-01

    Objective To evaluate the efficacy and long-term outcomes of regional intra-arterial chemotherapy for the treatment of advanced malignant solid tumors in children.Methods During Jul 1999 and Dec 2006,regional intra-arterial chemotherapy was performed in 15 patients (aging from 0.5 to 12 years,6 males and 9 females) with advanced malignant solid tumors in various parts of their bodies.In all the eases,13 accepted preoperative treatment and 2 accepted postoperative treatment.The tumors included rhabdomyosarcoma (2 cases in pelvis,2 in vagina and 1 in bladder),endodermal sinus tumor (3 in sacroiliac and 1 in colic omentum),malignant teratoma (1 in ovary and 1 in cerebellum),desmoplastic small round cell tumor (1 in abdomen),pancreablastoma (1 in root of mesentery),ependymoma (1 in cerebellum) and dermatofibrosareoma (1 in upper arm).Transcatheter arterial infusion chemotherapy (TAIC) of cisplatin,pirarubicin and vindesine was performed with the doses as follows:cisplatin 80 mg/m2,pirarubicin 40 mg/m2 and vindesine 3 mg/m2.Internal lilac artery was chosen as the route of administration for tumors in pelvis,bladder and vagina,internal I|iac artery and coccygeal artery for tumors in sacroiliac,superior mesenteric artery for tumors in abdomen,branch of brachial artery for tumors in upper arm and vertebral artery for tumors in cerebellum.TAIC was repeated every 4 weeks.In the intermission of TALC,intravenous systemic chemotherapy with vindesine,VP16,and ephosphamide were administered.Results In the period of chemotherapy,no cardiotoxicity,nephrotoxicity or hepatic dysfunction were observed except for grade Ⅰ-Ⅱ bone marrow suppression.One patient with ependymoma in the cerebellum got mild hemiplegia and recovered 4 weeks later.The tumors of the 13 patients accepting preoperative treatment were significantly shrunken,localized and could be completely resected.Remnant tumors of the 2 patients who underwent postoperative TAIC disappeared with no recurrence

  14. Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL may improve renal outcome of acute contrast media induced nephropathy: A randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study

    Directory of Open Access Journals (Sweden)

    Stiegler Philipp

    2011-08-01

    Full Text Available Abstract Background Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN. Neutrophil gelatinase-associated lipocalin (NGAL, a new biomarker predictive for acute kidney injury (AKI, has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. Methods/Design The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death. We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the

  15. Bridging intravenous-intra-arterial rescue strategy increases recanalization and the likelihood of a good outcome in nonresponder intravenous tissue plasminogen activator-treated patients: a case-control study.

    Science.gov (United States)

    Rubiera, Marta; Ribo, Marc; Pagola, Jorge; Coscojuela, Pilar; Rodriguez-Luna, David; Maisterra, Olga; Ibarra, Bernardo; Piñeiro, Socorro; Meler, Pilar; Romero, Francisco J; Alvarez-Sabin, Jose; Molina, Carlos A

    2011-04-01

    Safety and efficacy of the "bridging therapy" (intra-arterial [IA] reperfusion rescue for nonresponder intravenous [IV] tissue plasminogen activator [tPA]-treated patients) is a matter of debate. Our aim was to compare IV and IV-IA thrombolysis using a case-control approach. Consecutive patients with proximal intracranial occlusion who received IA reperfusion procedures after unsuccessful IV tPA (lack of clinical improvement and arterial recanalization 1 hour after tPA bolus) were studied (IV-IA group). They were compared with occluded vessel, clot location, stroke severity, and time to treatment-matched 1 to 2 historical patients from our prospective IV tPA database with persistent occlusion 1 hour after IV tPA (IV-NR group). Arterial occlusion and recanalization were assessed with transcranial Doppler. Clinical evaluation was assessed by National Institutes of Health Stroke Scale at baseline, 24 hours, and at discharge. Symptomatic intracranial hemorrhage was defined according to the National Institute of Neurological Disorders and Stroke trial. Functional evaluation was determined by modified Rankin Scale, being functional independency defined by modified Rankin Scale score ≤2. Forty-two IV-IA patients were compared with 84 matched IV-NR. Mean age was 71.5±2.9 years, 58 (46%) were women, and baseline median National Institutes of Health Stroke Scale score was 20 (interquartile range, 5). Mean time from symptoms to IV tPA was 176.9±113 minutes. On transcranial Doppler, complete recanalization was significantly higher in IV-IA than control subjects (12 hours: 45.2% versus 18.1%, P=0.002; 24 hours: 46.3% versus 25.3%, P=0.016) with nonsignificant better clinical evolution at 24 hours (40.5% versus 30.1%, P=0.169) and discharge (52.5% versus 39.5%, P=0.123). Symptomatic intracranial hemorrhage was similar (IV-IA 11.9% versus IV-NR 6%, P=0.205). Mortality at 3 months was 50% in the IV-IA group and 35.8% in the IV-NR (P=0.154). Forty percent of IV-IA patients were

  16. Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL) may improve renal outcome of acute contrast media induced nephropathy: a randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study).

    Science.gov (United States)

    Schilcher, Gernot; Ribitsch, Werner; Otto, Ronald; Portugaller, Rupert H; Quehenberger, Franz; Truschnig-Wilders, Martini; Zweiker, Robert; Stiegler, Philipp; Brodmann, Marianne; Weinhandl, Klemens; Horina, Joerg H

    2011-08-17

    Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated lipocalin (NGAL), a new biomarker predictive for acute kidney injury (AKI), has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM) application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death.We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the treatment arm if 1200 patients are recruited into the

  17. Channel's Concurrence and Quantum Teleportation

    Institute of Scientific and Technical Information of China (English)

    LING Yin-Sheng

    2005-01-01

    Concurrence can measure the entanglement property of a system. If the channel is a pure state, positive concurrence state can afford the good performance in the teleportation process. If the channel ia a mixed state, positive concurrence state cannot assure the good performance in the teleportation. The conditions of the positive concurrence and the quantum teleportation in the Heisenberg spin ring is derived.

  18. Radiation recall phenomenon presenting as myositis triggered by carboplatin plus paclitaxel and related literature review.

    Science.gov (United States)

    Maeng, Chi Hoon; Park, Jun Sang; Lee, Seung Ah; Kim, Dong Hwan; Yun, Dong Hwan; Yoo, Seung-Don; Kim, Hee-Sang; Chon, Jinmann

    2014-01-01

    While most case reports to date are radiation recall dermatitis, radiation recall myositis, which is a distinct form of radiation recall phenomenon caused by carboplatin plus paclitaxel, has not been reported. We treated a 57-year-old female patient who suffered from recurrent cervical cancer. When the patient developed a new left sacral metastasis, salvage radiotherapy (total dose 60 Gy) was administered. Four weeks later, chemotherapy using carboplatin plus paclitaxel was initiated. Four months after chemotherapy, the patient complained of severe pain in her left buttock. On magnetic resonance imaging (MRI), edematous changes and increased signal densities of left gluteus maximus and medius muscles were noted suggesting myositis. The border of the high signal intensity territory of the muscles was sharp and clearly corresponded with the recent irradiation field. We concluded that the patient had radiation recall myositis triggered by paclitaxel-carboplatin. Symptoms were controlled by analgesics, and there was no recurrence.

  19. Radiation recall phenomenon presenting as myositis triggered by carboplatin plus paclitaxel and related literature review

    Directory of Open Access Journals (Sweden)

    Chi Hoon Maeng

    2014-01-01

    Full Text Available While most case reports to date are radiation recall dermatitis, radiation recall myositis, which is a distinct form of radiation recall phenomenon caused by carboplatin plus paclitaxel, has not been reported. We treated a 57-year-old female patient who suffered from recurrent cervical cancer. When the patient developed a new left sacral metastasis, salvage radiotherapy (total dose 60 Gy was administered. Four weeks later, chemotherapy using carboplatin plus paclitaxel was initiated. Four months after chemotherapy, the patient complained of severe pain in her left buttock. On magnetic resonance imaging (MRI, edematous changes and increased signal densities of left gluteus maximus and medius muscles were noted suggesting myositis. The border of the high signal intensity territory of the muscles was sharp and clearly corresponded with the recent irradiation field. We concluded that the patient had radiation recall myositis triggered by paclitaxel-carboplatin. Symptoms were controlled by analgesics, and there was no recurrence.

  20. 尿激酶动脉溶栓与重组组织型纤溶酶原激活剂静脉溶栓治疗急性缺血性卒中的疗效比较%Comparative efficacy of intra-arterial thrombolysis with urokinase and intravenous thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    周俊山; 徐梦怡

    2010-01-01

    Objective To evaluate the efficacy and safety of intra-arterial thrombolysis with urokinase and intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke. Methods A total of 43 patients with acute ischemic stroke within 6 hours of onset were included, 31 of them underwent superselective intra-arterial thrombolysis in the intra-arterial thrombolysis group and 12 of them underwent intravenous thrombolysis with rtPA in the intravenous thrombolysis group. Vascular recanalization was observed in the intra-arterial thrombolysis group, and the modified Rankin scale (mRS) scores at day 90 were used to evaluate the outcomes in both groups. Results Eighteen patients (58.1%) had complete recanalization and 7 (22.6%) had partial recanalization in the intra-arterial thrombolysis group. The recanalization rate was 80.6%, 3 complicated symptomatic intracranial hemorrhage, and 1 died. There vere no significant differences between the good outcome rate (74.2% vs. 66.7%, x2 =0.24, P=0.622) and the incidence of symptomatic intracranial hemorrhage at 90 d (9. 68% vs. 8. 33%, x2 =0. 19, P =0. 892). Conclusions Urokinase intra arterial thrombolysis within the time window can significantly improve the recanalization rate of the occluded vessels and improve the clinical symptoms of the patents in acute phase and long term outcomes. Their short-term efficacy and long-term outcomes are almost the same with intrave nous thrombolysis with rtPA.%目的 评价尿激酶动脉溶栓与重组组织纤溶酶原激活剂(recombinant tissue plasminogen activator,rtPA)静脉溶栓治疗急性缺血性卒中的疗效和安全性.方法 发病6 h内的急性脑梗死患者43例,其中动脉溶栓组31例行超选择性动脉溶栓,静脉溶栓组12例行rtPA静脉溶栓.观察动脉溶栓组血管再通.90 d时改良Rankin量表(modified Ranlkin scale,mRS)评分评价2组转归.结果 动脉溶栓组完全再通18例(58.1%),部分再通7例(22.6%),

  1. Adjuvant Carboplatin Treatment in 115 Patients With Stage I Seminoma: Retrospective Multicenter Survey.

    Science.gov (United States)

    Diminutto, Alberto; Basso, Umberto; Maruzzo, Marco; Morelli, Franco; De Giorgi, Ugo; Perin, Alessandra; Fraccon, Anna Paola; Lo Re, Giovanni; Rizzi, Anna; Sava, Teodoro; Fornarini, Giuseppe; Valcamonico, Francesca; Zustovich, Fable; Massari, Francesco; Zanardi, Elisa; Roma, Anna; Zattoni, Filiberto; Zagonel, Vittorina

    2016-04-01

    The administration of carboplatin AUC 7 has become a standard adjuvant option for patients undergoing orchiectomy for stage I seminoma, in alternative to radiotherapy on retroperitoneal lymphnodes or surveillance. The toxicity of AUC 7 carboplatin appeared manageable in the pivotal trial of Oliver et al, but dose ranges were not reported. Fear of toxicity may induce arbitrary dose reductions, which may potentially compromise patients' outcome. We reviewed adjuvant carboplatin administration in 115 stage I seminoma patients followed in 11 Italian medical oncology centers since 2005. Clinical and pathological data, modality of carboplatin dose calculation, dose reductions, toxicities, and relapses were recorded. Median age was 35 years (range, 18-65 years), adverse prognostic factors were either T ≥ 4 cm (17.4%) or rete testis invasion (28.7%), both of them (35.7%), none or unspecified (18.3%). GFR was estimated mainly by Cockroft-Gault formula (55.7%) or Jeliffe formula (26.1%), with a median of 105 mL/min (range, 75-209 mL/min). The median dose of carboplatin was 900 mg (range, 690-1535 mg). A dose reduction > 10% was applied to 14 patients. Toxicities were mild fatigue, moderate nausea/vomiting, 5.2% of grade 3 to 4 thrombocytopenia. After a median follow-up of 22.1 months, 5.2% of patients have relapsed in the retroperitoneal lymph nodes. None of the patients that relapsed were treated with reduced dose. All but one achieved complete remission with salvage chemotherapy. Adjuvant AUC 7 carboplatin reduce relapses of stage I seminoma patients to 5.2%, with manageable toxicities. Dose reductions should be proscribed. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. A randomized phase II study of carboplatin plus pegylated liposomal doxorubicin versus carboplatin plus paclitaxel in platinum sensitive ovarian cancer patients: a Hellenic Cooperative Oncology Group study

    Directory of Open Access Journals (Sweden)

    Briasoulis Evangelos

    2010-01-01

    Full Text Available Abstract Background Platinum-based combinations are the standard second-line treatment for platinum-sensitive ovarian cancer (OC. This randomized phase II study was undertaken in order to compare the combination of carboplatin and pegylated liposomal doxorubicin (LD with carboplatin and paclitaxel (CP in this setting. Methods Patients with histologically confirmed recurrent OC, at the time of or more than 6 months after platinum-based chemotherapy, were randomized to six cycles of CP (carboplatin AUC5 + paclitaxel 175 mg/m2, d1q21 or CLD (carboplatin AUC5 + pegylated LD 45 mg/m2, d1q28. Results A total of 189 eligible patients (CP 96, CLD 93, with a median age of 63 years, median Performance Status (PS 0 and a median platinum free interval (PFI of 16.5 months, entered the study. Discontinuation due to toxicity was higher in the CP patients (13.5% versus 3%, P = 0.016. The overall response rate was similar: CP 58% versus CLD 51%, P = 0.309 (Complete Response; CR 34% versus 23% and there was no statistical difference in time-to-progression (TTP or overall survival (OS; TTP 10.8 months CP versus 11.8 CLD, P = 0.904; OS 29.4 months CP versus 24.7 CLD, P = 0.454. No toxic deaths were recorded. Neutropenia was the most commonly seen severe toxicity (CP 30% versus CLD 35%. More frequent in CLD were severe thrombocytopenia (11% versus 2%, P = 0.016, skin toxicity and Palmar-plantar erythrodysesthesia (PPE grade 1-2 (38% versus 9%, PP = 0.029, 20% versus 5%, P = 0.003. PS and PFI were independent prognostic factors for TTP and OS. Conclusions The combination of pegylated LD with carboplatin is effective, showing less neurotoxicity and alopecia than paclitaxel-carboplatin. It thus warrants a further phase III evaluation as an alternative treatment option for platinum-sensitive OC patients. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12609000436279

  3. Building Safe Concurrency Abstractions

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    2014-01-01

    into the notions of concurrent and alternating objects. Alternating objects may be used to start a cooperative thread for each possible blocking communication and is thus an alternative to asynchronous messages and guarded commands. Beta like SIMULA, the first OO language, was designed as a language for modeling...... as well as programming, and we describe how this has had an impact on the design of the language. Although Beta supports the definition of high-level concurrency abstractions, the use of these rely on the discipline of the programmer as is the case for Java and other mainstream OO languages. We introduce...

  4. The cytotoxic activity of cisplatin, carboplatin and teniposide alone and combined determined on four human small cell lung cancer cell lines by the clonogenic assay

    DEFF Research Database (Denmark)

    Roed, H; Vindeløv, L L; Christensen, I J

    1988-01-01

    culture medium. By combining either cisplatin or carboplatin with teniposide additive cell kill was obtained. Additivity was also obtained when cisplatin was combined with carboplatin. Since the two drugs have a different toxicity pattern a clinical synergy may be obtained by combined use of these two......Using the clonogenic assay to compare the cytotoxic activity of cisplatin and carboplatin on four human small cell lung cancer cell lines, cisplatin was shown to be equally or more potent than carboplatin at equitoxic doses with 1 h incubation. Increased potency of carboplatin was revealed when...

  5. Adjuvant treatment for Stage I seminoma: Why radiotherapy is better than carboplatin.

    Science.gov (United States)

    Yathiraj, Prahlad H; Sharan, Krishna; Fernandes, Donald J; Vidyasagar, M S

    2016-01-01

    Adjuvant treatment options for Stage I seminoma include active surveillance, chemotherapy, and radiotherapy. Active surveillance may not be ideal for the average Indian patient. Of the two accepted adjuvant therapy options, namely single-dose carboplatin chemotherapy and radiotherapy to the retroperitoneal nodes, though it intuitively appears more appealing, a deeper review reveals the potential drawbacks of chemotherapy. This article highlights the misconceptions regarding carboplatin and provides reasons for an argument why radiotherapy is better when a patient with Stage I seminoma chooses to undergo adjuvant treatment.

  6. 选择性动脉钙刺激后肝静脉血清胰岛素测定用于胰岛素瘤定位的研究%Localization of pancreatic insulinomas by measurement of serum insulin in hepatic vein after selective intra-arterial calcium stimulation

    Institute of Scientific and Technical Information of China (English)

    党同科; 陈曦; 周光文

    2011-01-01

    Objective To evaluate the clinical value of selective intra-arterial calcium stimulated venous sampling ( ASVS) for the localization of pancreatic insulinoma preoperatively.Methods The clinical data of 28 insulinoma patients admitted from May 2000 to June 2010 in Ruijin Hospital undergoing selective intra-arterial calcium stimulated venous sampling with diagnosis of insulinomas before surgery were analyzed retrospectively.Results There were 12 males and 16 females.All the patients had Whipple's triad, and with proved insulinomas by postoperative pathology.There were 26 cases of single insulinoma and 2 cases of multiple insulinomas with altogether 32 insulinomas resected.78.1% of insulinomas were less than 20 mm.All patient were examined by selective intra-arterial calcium stimulated venous sampling.The peak ratio of insulin to the baseline after calcium stimulation appeared at the superior mensenteric artery (SMA) in 6 cases, and the peak ratio of insulin to the baseline after calcium stimulation appeared at gastroduodenal artery(GDA), proximal splenic artery (SAP) and distal splenic artery (SAD) in 9 cases, 6 cases and 6 cases respectively; Selective intra-arterial calcium stimulated venous sampling accurately located 25 cases, and selective intra-arterial calcium stimulated venous sampling located 2 cases wrongly.In one patient, the selective intra-arterial calcium stimulated venous sampling was falsely negative.The mean and median peak ratio of insulin to the baseline after calcium stimulation were 8.8 folds and 14.8 folds respectively.Accurate rate of selective intra-arterial calcium stimulated venous sampling was 89.3% (25/28) and it was higher than that of computed tomography (CT) (56.5% ) , magnetic resonance imaging (MRI) (60.0%).Sensitivity of selective intra-arterial calcium stimulated venous sampling was 96.2%, which was higher than that of computed tomography ( 69.6% ) , magnetic resonance imaging (75.0% ).Conclusion Selective intra-arterial calcium

  7. Coalgebra, concurrency and control

    NARCIS (Netherlands)

    J.J.M.M. Rutten (Jan)

    1999-01-01

    textabstractCoalgebra is used to generalize notions and techniques from concurrency theory, in order to apply them to problems concerning the supervisory control of discrete event systems. The main ingredients of this approach are the characterization of controllability in terms of (a variant of)

  8. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...

  9. Composing Concurrent Objects

    NARCIS (Netherlands)

    Bergmans, Lodewijk

    1994-01-01

    Adopting the object-oriented paradigm for the development of large and complex software systems offers several advantages, of which increased extensibility and reusability are the most prominent ones. The object-oriented model is also quite suitable for modelling concurrent systems. However, it

  10. L-carnitine protects against carboplatin-mediated renal injury: AMPK- and PPARα-dependent inactivation of NFAT3.

    Directory of Open Access Journals (Sweden)

    Yuh-Mou Sue

    Full Text Available We have previously shown that carboplatin induces inflammation and apoptosis in renal tubular cells (RTCs through the activation of the nuclear factor of activated T cells-3 (NFAT3 protein by reactive oxygen species (ROS, and that the ROS-mediated activation of NFAT3 is prevented by N-acetyl cysteine and heme oxygenase-1 treatment. In the current study, we investigated the underlying molecular mechanisms of the protective effect of L-carnitine on carboplatin-mediated renal injury. Balb/c mice and RTCs were used as model systems. Carboplatin-induced apoptosis in RTCs was examined using terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling. We evaluated the effects of the overexpression of the peroxisome-proliferator-activated receptor alpha (PPARα protein, the knockdown of PPARα gene, and the blockade of AMPK activation and PPARα to investigate the underlying mechanisms of the protective effect of L-carnitine on carboplatin-mediated renal injury. Carboplatin reduced the nuclear translocation, phosphorylation, and peroxisome proliferator responsive element transactivational activity of PPARα. These carboplatin-mediated effects were prevented by L-carnitine through a mechanism dependent on AMPK phosphorylation and subsequent PPARα activation. The activation of PPARα induced cyclooxygenase 2 (COX-2 and prostacyclin (PGI2 synthase expression that formed a positive feedback loop to further activate PPARα. The coimmunoprecipitation of the nuclear factor (NF κB proteins increased following the induction of PPARα by L-carnitine, which reduced NFκB transactivational activity and cytokine expression. The in vivo study showed that the inactivation of AMPK suppressed the protective effect of L-carnitine in carboplatin-treated mice, indicating that AMPK phosphorylation is required for PPARα activation in the L-carnitine-mediated protection of RTC apoptosis caused by carboplatin. The results of our study provide molecular evidence

  11. Methylseleninic acid sensitizes Notch3-activated OVCA429 ovarian cancer cells to carboplatin

    Science.gov (United States)

    Ovarian cancer, the deadliest of gynecologic cancers, is usually diagnosed at advanced stage due to invalidated screening test and non-specific symptoms presented. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-c...

  12. On the hydrolysis mechanism of the second-generation anticancer drug carboplatin.

    Science.gov (United States)

    Pavelka, Matej; Lucas, Maria Fatima A; Russo, Nino

    2007-01-01

    The hydrolysis reaction mechanisms of carboplatin, a second-generation anticancer drug, have been explored by combining density functional theory (DFT) with the conductor-like dielectric continuum model (CPCM) approach. The decomposition of carboplatin in water is expected to take place through a biphasic mechanism with a ring-opening process followed by the loss of the malonato ligand. We have investigated this reaction in water and acid conditions and established that the number of protons present in the malonato ligand has a direct effect on the energetics of this system. Close observation of the optimised structures revealed a necessary systematic water molecule in the vicinity of the amino groups of carboplatin. For this reason we have also investigated this reaction with an explicit water molecule. From the computed potential-energy surfaces it is established that the water hydrolysis takes place with an activation barrier of 30 kcal mol(-1), confirming the very slow reaction observed experimentally. The decomposition of carboplatin upon acidification was also investigated and we have computed a 21 kcal mol(-1) barrier to be overcome (experimental value 23 kcal mol(-1)). We have also established that the rate-limiting process is the first hydration, and ascertained the importance of a water molecule close to the two amine groups in lowering the activation barriers for the ring-opening reaction.

  13. Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study

    DEFF Research Database (Denmark)

    Hillerdal, G.; Sundstrom, S.; Riska, H.

    2008-01-01

    BACKGROUND: Malignant pleural mesothelioma has a poor prognosis and there is limited effect of treatment. The Nordic Mesothelioma groups decided in the year 2000 to investigate a combination of liposomized doxorubicin, carboplatin, and gemcitabine for this disease in a phase II study. METHODS: From...

  14. Treatment of advanced seminoma with cyclophosphamide, vincristine and carboplatin on an outpatient basis

    NARCIS (Netherlands)

    Sleijfer, S; Willemse, PHB; deVries, EGE; vanderGraaf, WTA; Mulder, NH; Schraffordt Koops, H.

    This study describes the efficacy and toxicity of a combination regimen consisting of cyclophosphamide, vincristine (oncovin) and carboplatin (COC) for advanced seminoma on an outpatient basis. Twenty-seven patients (mean age 43 years, range 28-63 years) were classified as stage IIC (n = 5), stage

  15. Characterization and carboplatin loaded chitosan nanoparticles for the chemotherapy against breast cancer in vitro studies.

    Science.gov (United States)

    Khan, Md Asad; Zafaryab, Md; Mehdi, Syed Hassan; Quadri, Javed; Rizvi, M Moshahid A

    2017-04-01

    Aim of the studies to synthesized chitosan nanoparticles by an ionic interaction procedure. The nanoparticles were characterized by physicochemical methods like, DLS, TEM, Surface potential measurements, FT-IR and DSC. The average particle size of chitosan and carboplatin nanoparticles was found to be 277.25±11.37nm and 289.30±8.15nm and zeta potential was found to be 31±3.14mV and 33±2.15mV respectively with low polydispersity index. The maximum entrapment of carboplatin in nanoparticles was a spherical shape with a positive charge. The maximum encapsulation and loading efficiencies of carboplatin (5mg/ml) were obtained to be 58.43% and 13.27% respectively. The nanocarboplatin was better blood compatibility as compared to chitosan nanoparticles. Finally, the cytotoxic effects of the carboplatin loaded chitosan nanoparticles were tested in-vitro against breast cancer (MCF-7) cell lines. Our studies showed that the chitosan nanoparticles could be used as a promising candidate for drug delivery for the therapeutic treatment of breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. The effect of consolidation treatment with intraperitoneal carboplatin in advanced epithelial ovarian cancers

    Directory of Open Access Journals (Sweden)

    Azamsadat Mousavi

    2014-07-01

    Conclusion: It seems that consolidation therapy with intraperitoneal carboplatin may not increase overall survival, reduce relapse rate or decrease mortality, though it does not induce considerable side effects. Since the mean survival in the intervention group was nine months more than controls, this difference may be clinically significant.

  17. Cisplatin or carboplatin in the treatment of non-small cell lung cancer: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Andrea Ardizzoni

    2011-12-01

    Full Text Available Cisplatin has a pivotal role in the treatment of non-small cell lung cancer (NSCLC. However, it is associated with a number of serious and unpleasant side effects (nausea-vomiting, myelo-suppression, neuro-toxicity and renal function impairment. To overcome these limitations, most clinicians have turned towards the use of the cisplatin analog carboplatin, which is associated with a lower incidence of toxicity. Although carboplatin and cisplatin have a similar mechanism of action and pre-clinical spectrum of activity, it is still unclear whether they actually have the same clinical efficacy in all types of tumors. While for some tumors, such as ovarian cancer, equivalent efficacy has been convincingly proven, for others, such as germ cell and headneck tumors, there is some evidence that carboplatin is inferior to cisplatin. It has never been convincingly proven that carboplatin and cisplatin have the same efficacy in the treatment of NSCLC. This review provides an update of available evidences about this important scientific question.

  18. Delivery of carboplatin by carbon-based nanocontainers mediates increased cancer cell death

    Energy Technology Data Exchange (ETDEWEB)

    Arlt, M; Fuessel, S; Kraemer, K; Wirth, M P [Department for Urology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Fetscherstrasse 74, 01307 Dresden (Germany); Haase, D; Hampel, S; Oswald, S; Bachmatiuk, A; Klingeler, R; Ritschel, M; Leonhardt, A; Buechner, B [Leibniz Institute for Solid State and Materials Research (IFW), Helmholtzstrasse 20, 01069 Dresden (Germany); Schulze, R, E-mail: kai.kraemer@uniklinikum-dresden.de [Bioanalytical Chemistry, Technische Universitaet Dresden, Bergstrasse 66, 01069 Dresden (Germany)

    2010-08-20

    Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of nanocarriers seems to be an efficient and promising approach for drug delivery. Their chemical and mechanical stability and their possible multifunctionality render tubular nanomaterials, such as carbon nanotubes (CNTs) and carbon nanofibres (CNFs), promising delivery agents for anticancer drugs. The goal of the present study was to investigate CNTs and CNFs in order to deliver carboplatin in vitro. No significant intrinsic toxicity of unloaded materials was found, confirming their biocompatibility. Carboplatin was loaded onto CNTs and CNFs, revealing a loading yield of 0.20 mg (CNT-CP) and 0.13 mg (CNF-CP) platinum per milligram of material. The platinum release depended on the carrier material. Whereas CNF-CP marginally released the drug, CNT-CP functioned as a drug depot, constantly releasing up to 68% within 14 days. The cytotoxicity of CNT-CP and CNF-CP in urological tumour cell lines was dependent on the drug release. CNT-CP was identified to be more effective than CNF-CP concerning the impairment of proliferation and clonogenic survival of tumour cells. Moreover, carboplatin, which was delivered by CNT-CP, exhibited a higher anticancer activity than free carboplatin.

  19. Dacarbazine DTIC and carboplatin as an outpatient treatment for disseminated malignant melanoma

    NARCIS (Netherlands)

    Nieboer, P; Mulder, NH; Van Der Graaf, WTA; Willemse, PHB; Hospers, GAP

    2001-01-01

    Occasionally long-term survival in disseminated melanoma can be obtained through chemotherapy, We treated 22 patients with disseminated melanoma with an outpatient regimen consisting of dacarbazine (DTIC) and carboplatin. Three patients had a complete response lasting 4+, 9 and 9 months (survival

  20. Chemical conversion of cisplatin and carboplatin with histidine in a model protein crystallized under sodium iodide conditions

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M.; Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    Crystals of HEWL with cisplatin and HEWL with carboplatin grown in sodium iodide conditions both show a partial chemical transformation of cisplatin or carboplatin to a transiodoplatin (PtI{sub 2}X{sub 2}) form. The binding is only at the N{sup δ} atom of His15. A further Pt species (PtI{sub 3}X) is also seen, in both cases bound in a crevice between symmetry-related protein molecules. Cisplatin and carboplatin are platinum anticancer agents that are used to treat a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine in hen egg-white lysozyme (HEWL) showed a partial chemical conversion of carboplatin to cisplatin owing to the high sodium chloride concentration used in the crystallization conditions. Also, the co-crystallization of HEWL with carboplatin in sodium bromide conditions resulted in the partial conversion of carboplatin to the transbromoplatin form, with a portion of the cyclobutanedicarboxylate (CBDC) moiety still present. The results of the co-crystallization of HEWL with cisplatin or carboplatin in sodium iodide conditions are now reported in order to determine whether the cisplatin and carboplatin converted to the iodo form, and whether this took place in a similar way to the partial conversion of carboplatin to cisplatin in NaCl conditions or to transbromoplatin in NaBr conditions as seen previously. It is reported here that a partial chemical transformation has taken place to a transplatin form for both ligands. The NaI-grown crystals belonged to the monoclinic space group P2{sub 1} with two molecules in the asymmetric unit. The chemically transformed cisplatin and carboplatin bind to both His15 residues, i.e. in each asymmetric unit. The binding is only at the N{sup δ} atom of His15. A third platinum species is also seen in both conditions bound in a crevice between symmetry-related molecules. Here, the platinum is bound to three I atoms identified based on their anomalous difference electron densities

  1. A Concurrent Logical Relation

    DEFF Research Database (Denmark)

    Birkedal, Lars; Sieczkowski, Filip; Thamsborg, Jacob Junker

    2012-01-01

    We present a logical relation for showing the correctness of program transformations based on a new type-and-effect system for a concurrent extension of an ML-like language with higher-order functions, higher-order store and dynamic memory allocation. We show how to use our model to verify a number...... of interesting program transformations that rely on effect annotations. In particular, we prove a Parallelization Theorem, which expresses when it is sound to run two expressions in parallel instead of sequentially. The conditions are expressed solely in terms of the types and effects of the expressions....... To the best of our knowledge, this is the first such result for a concurrent higher-order language with higher-order store and dynamic memory allocation....

  2. Algebraic topology and concurrency

    DEFF Research Database (Denmark)

    Fajstrup, Lisbeth; Raussen, Martin; Goubault, Eric

    2006-01-01

    We show in this article that some concepts from homotopy theory, in algebraic topology,are relevant for studying concurrent programs. We exhibit a natural semantics of semaphore programs, based on partially ordered topological spaces, which are studied up to “elastic deformation” or homotopy......, giving information about important properties of the program, such as deadlocks, unreachables, serializability, essential schedules, etc. In fact, it is not quite ordinary homotopy that has to be used, but rather a “directed homotopy” that does not reverse the flow of time. We show some of the essential...... differences between ordinary and directed homotopy through examples. We also relate the topological view to a combinatorial view of concurrent programs closer to transition systems, through the notion of a cubical set. Finally we apply some of these concepts to the proof of the safeness of a two...

  3. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...... with piecewise-smooth boundary. Our aim is to identify the equivalence classes with the critical points of a certain Morse function....

  4. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...... with piecewise-smooth boundary. Our aim is to identify the equivalence classes with the critical points of a certain Morse function....

  5. Feature conversion for concurrent engineering

    NARCIS (Netherlands)

    De Kraker, J.K.

    1998-01-01

    Feature conversion for concurrent engineering integrates two modern product development paradigms. Concurrent engineering is a product development paradigm in which multiple engineering disciplines participate. It optimizes a product with respect to available resources and product quality, for which

  6. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...... topological reasoning in which there is no information about relation "in time" among points. The main task is to define equivalence of paths reflecting execution of a program. We use the notion of homotopy history equivalence relation. The model space considered in this work is a differentiable manifold...

  7. Mastering concurrency in Go

    CERN Document Server

    Kozyra, Nathan

    2014-01-01

    A practical approach covering everything you need to know to get up and running with Go, starting with the basics and imparting increasingly more detail as the examples and topics become more complicated. The book utilizes a casual, conversational style, rife with actual code and historical anecdotes for perspective, as well as usable and extensible example applications. This book is intended for systems developers and programmers with some experience in either Go and/or concurrent programming who wish to become fluent in building high-performance applications that scale by leveraging single-c

  8. 4-step 4-h carboplatin desensitization protocol for patients with gynecological malignancies showing platinum hypersensitivity: a retrospective study.

    Science.gov (United States)

    Takase, Naoto; Matsumoto, Koji; Onoe, Takuma; Kitao, Akihito; Tanioka, Maki; Kikukawa, Yoshitaka; Yamaguchi, Satoshi; Fujiwara, Kiyoshi; Negoro, Shunichi

    2015-06-01

    Platinum agents are essential for treating gynecological malignancies, particularly ovarian cancer. However, multiple carboplatin doses may cause hypersensitivity reactions (HSRs). Carboplatin desensitization prevents life-threatening HSRs and promotes the successful completion of planned chemotherapy. Since January 2010, carboplatin desensitization was performed at our institution. Solutions with 1/1000, 1/100, and 1/10 dilutions of carboplatin and an undiluted solution were prepared in 250 mL of 5% glucose. Each solution was administered as a 1-h intravenous infusion (4-step 4-h protocol). This retrospective analysis was approved by the institutional review board. From January 2010 to December 2013, 20 patients with gynecological malignancies (median age 62 years, range 43-74 years) received desensitization treatment. The International Federation of Gynecology and Obstetrics stages at presentation were I, II, III, and IV in 1, 1, 15, 13 patients, respectively. During first-line and second-line treatments, 3 and 17 patients, respectively, experienced carboplatin-induced HSRs. The median carboplatin cycle number was 11 (range 2-16). In the first desensitization cycle, 17 (85%) patients completed treatment without adverse events, 2 experienced Grade 1 HSRs but completed treatment, and 1 experienced Grade 3 HSR and discontinued treatment. The first desensitization cycle completion rate was 95%. Of 83 desensitization cycles administered, 79 (95.2%) were completed. No treatment-related deaths occurred. Most patients completed the planned chemotherapy. Our protocol could be conducted safely with shorter duration and simpler procedures than previous protocols. Carboplatin desensitization seems beneficial for patients with a history of carboplatin-induced HSRs; however, the risk of HSR recurrence still remains. Desensitization should therefore be performed only by well-trained staff.

  9. Kinetics of carboplatin-DNA binding in genomic DNA and bladder cancer cells as determined by accelerator mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Hah, S S; Stivers, K M; Vere White, R; Henderson, P T

    2005-12-29

    Cisplatin and carboplatin are platinum-based drugs that are widely used in cancer chemotherapy. The cytotoxicity of these drugs is mediated by platinum-DNA monoadducts and intra- and interstrand diadducts, which are formed following uptake of the drug into the nucleus of cells. The pharmacodynamics of carboplatin display fewer side effects than for cisplatin, albeit with less potency, which may be due to differences in rates of DNA adduct formation. We report the use of accelerator mass spectrometry (AMS), a sensitive detection method often used for radiocarbon quantitation, to measure both the kinetics of [{sup 14}C]carboplatin-DNA adduct formation with genomic DNA and drug uptake and DNA binding in T24 human bladder cancer cells. Only carboplatin-DNA monoadducts contain radiocarbon in the platinated DNA, which allowed for calculation of kinetic rates and concentrations within the system. The percent of radiocarbon bound to salmon sperm DNA in the form of monoadducts was measured by AMS over 24 h. Knowledge of both the starting concentration of the parent carboplatin and the concentration of radiocarbon in the DNA at a variety of time points allowed calculation of the rates of Pt-DNA monoadduct formation and conversion to toxic cross-links. Importantly, the rate of carboplatin-DNA monoadduct formation was approximately 100-fold slower than that reported for the more potent cisplatin analogue, which may explain the lower toxicity of carboplatin. T24 human bladder cancer cells were incubated with a subpharmacological dose of [{sup 14}C]carboplatin, and the rate of accumulation of radiocarbon in the cells and nuclear DNA was measured by AMS. The lowest concentration of radiocarbon measured was approximately 1 amol/10 {micro}g of DNA. This sensitivity may allow the method to be used for clinical applications.

  10. Influence of mesna on the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.

    Science.gov (United States)

    Kangarloo, Shahbal B; Gangopadhyay, Suman B; Syme, Rachel M; Wolff, Johannes E A; Glück, Stefan

    2004-01-01

    Mesna, a reactive thiol, often encounters cisplatin and carboplatin in combination protocols involving oxazaphosphorines and platinum drugs. This co-administration might be unfavorable based on the inactivation of platinum drugs by thiol groups in vitro. We investigated whether mesna influences the pharmacokinetics of platinum drugs when co-administered with cisplatin or carboplatin. The pharmacokinetics of platinum drugs were investigated in 18 pediatric patients receiving either cisplatin or carboplatin in a combination with or without mesna. In cisplatin patients, a decrease in the distribution clearance of total platinum was observed when mesna was co-administered (CLd, 2.2 +/- 0.1 mL/min.kg; n = 3), compared to cisplatin without mesna (CLd, 4.8 +/- 1.5 mL/min.kg; n = 5) (p = 0.029, t-test). This might have been caused by an influence of mesna in slowing down the protein binding of cisplatin since a trend (p = 0.057) in prolonged distribution half-life of total platinum was also observed when mesna was present (t(1/2a) 65 +/- 21 min; n = 3) compared to cisplatin without mesna (t(1/2a), 32 +/- 18 min; n = 5). However, the impact of these changes on the area under the concentration time curve (AUC), total clearance (CLt), and volume of distribution (V) for total platinum and ultrafilterable platinum species was hardly noticeable. In carboplatin patients, when mesna was co-administered: AUC (2.5 +/- 0.4 mg.min/mL.400 mg/m2; n = 5) CLt, (6.8 +/- 5.1 mL/min.kg; n = 6), and V (0.7 +/- 0.4 L/kg; n = 6) for ultrafilterable platinum species were not significantly different from when carboplatin were administered without mesna: AUC (2.3 +/- 1.3 mg.min/mL.400 mg/m2; n = 4), CLt (5.8 +/- 4.6 mL/min.kg; n = 5), and V (1.1 +/- 1.1 L/kg; n = 5). Hence, mesna does not significantly influence the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.

  11. Recursive Concurrent Stochastic Games

    CERN Document Server

    Etessami, Kousha

    2008-01-01

    We study Recursive Concurrent Stochastic Games (RCSGs), extending our recent analysis of recursive simple stochastic games [16,17] to a concurrent setting where the two players choose moves simultaneously and independently at each state. For multi-exit games, our earlier work already showed undecidability for basic questions like termination, thus we focus on the important case of single-exit RCSGs (1-RCSGs). We first characterize the value of a 1-RCSG termination game as the least fixed point solution of a system of nonlinear minimax functional equations, and use it to show PSPACE decidability for the quantitative termination problem. We then give a strategy improvement technique, which we use to show that player 1 (maximizer) has \\epsilon-optimal randomized Stackless & Memoryless (r-SM) strategies for all \\epsilon > 0, while player 2 (minimizer) has optimal r-SM strategies. Thus, such games are r-SM-determined. These results mirror and generalize in a strong sense the randomized memoryless determinacy r...

  12. The cytotoxic activity of cisplatin, carboplatin and teniposide alone and combined determined on four human small cell lung cancer cell lines by the clonogenic assay

    DEFF Research Database (Denmark)

    Roed, H; Vindeløv, L L; Christensen, I J

    1988-01-01

    Using the clonogenic assay to compare the cytotoxic activity of cisplatin and carboplatin on four human small cell lung cancer cell lines, cisplatin was shown to be equally or more potent than carboplatin at equitoxic doses with 1 h incubation. Increased potency of carboplatin was revealed when...... the drugs were tested with continuous incubation, although cisplatin still was the most potent drug when compared on a microgram to microgram basis. This relative increase in potency of carboplatin can at least partly be explained by the development of a more reactive form of the drug when stored in tissue...

  13. Remission of recurrent cervical cancer with paclitaxel and carboplatin: a case report and review of literature.

    Science.gov (United States)

    Termrungruanglert, W; Kudelka, A P; Piamsomboon, S; Edwards, C L; Verschraegen, C F; Loyer, E; Kavanagh, J J

    1996-01-01

    We report the case of a patient with recurrent squamous cell carcinoma of the cervix, that metastasized to the paraaortic and supraclavicular lymph nodes and the lungs after primary radiotherapy for stage IIB. The tumor was refractory to multiple drug regimens. A combination of paclitaxel (135 mg/m2 intravenous infusion over 24) hours and carboplatin with a target area under the curve of 7.5 mg-min/mL were then administered and repeated every 4 weeks. The patient tolerated the chemotherapy well with myeloprotection from granulocyte colony-stimulating factor and the disease went into remission. Thus, the combination of paclitaxel and carboplatin may have antitumor activity in advanced or recurrent squamous cell carcinoma of the cervix.

  14. Domain Theory for Concurrency

    DEFF Research Database (Denmark)

    Nygaard, Mikkel

    a process is capable. HOPLA can directly encode calculi like CCS, CCS with process passing, and mobile ambients with public names, and it can be given a straightforward operational semantics supporting a standard bisimulation congruence. The denotational and operational semantics are related with simple...... and associated comonads, it highlights the role of linearity in concurrent computation. Two choices of comonad yield two expressive metalanguages for higher-order processes, both arising from canonical constructions in the model. Their denotational semantics are fully abstract with respect to contextual...... input necessary for it. Such a semantics is provided, based on event structures; it agrees with the presheaf semantics at first order and exposes the tensor operation as a simple parallel composition of event structures. The categorical model obtained from presheaves is very rich in structure and points...

  15. Concurrent Quantum Computation

    CERN Document Server

    Yamaguchi, F; Yamamoto, Y

    2000-01-01

    A quantum computer is a multi-particle interferometer that comprises beam splitters at both ends and arms, where the n two-level particles undergo the interactions among them. The arms are designed so that relevant functions required to produce a computational result is stored in the phase shifts of the 2^n arms. They can be detected by interferometry that allows us to utilize quantum parallelism. Quantum algorithms are accountable for what interferometers to be constructed to compute particular problems. A standard formalism for constructing the arms has been developed by the extension of classical reversible gate arrays. By its nature of sequential applications of logic operations, the required number of gates increases exponentially as the problem size grows. This may cause a crucial obstacle to perform a quantum computation within a limited decoherence time. We propose a direct and concurrent construction of the interferometer arms by one-time evolution of a physical system with arbitrary multi-particle i...

  16. Concurrent engineering research center

    Science.gov (United States)

    Callahan, John R.

    1995-01-01

    The projects undertaken by The Concurrent Engineering Research Center (CERC) at West Virginia University are reported and summarized. CERC's participation in the Department of Defense's Defense Advanced Research Project relating to technology needed to improve the product development process is described, particularly in the area of advanced weapon systems. The efforts committed to improving collaboration among the diverse and distributed health care providers are reported, along with the research activities for NASA in Independent Software Verification and Validation. CERC also takes part in the electronic respirator certification initiated by The National Institute for Occupational Safety and Health, as well as in the efforts to find a solution to the problem of producing environment-friendly end-products for product developers worldwide. The 3M Fiber Metal Matrix Composite Model Factory Program is discussed. CERC technologies, facilities,and personnel-related issues are described, along with its library and technical services and recent publications.

  17. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well...... as refutation of safety and liveness properties. However, the algorithmic construction of finite abstractions from potentially infinite concurrent processes is a missing link that prevents their more widespread usage for model checking of concurrent systems. Our algorithm is a worklist algorithm using concepts...

  18. Elevated β-catenin activity contributes to carboplatin resistance in A2780cp ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Barghout, Samir H. [Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Zepeda, Nubia; Xu, Zhihua [Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Steed, Helen [Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Lee, Cheng-Han [Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Fu, YangXin, E-mail: yangxin@ualberta.ca [Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada); Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB (Canada)

    2015-12-04

    Ovarian cancer is the fifth leading cause of cancer-related mortalities in women. Epithelial ovarian cancer (EOC) represents approximately 90% of all ovarian malignancies. Most EOC patients are diagnosed at advanced stages and current chemotherapy regimens are ineffective against advanced EOC due to the development of chemoresistance. It is important to better understand the molecular mechanisms underlying acquired resistance to effectively manage this disease. In this study, we examined the expression of the Wnt/β-catenin signaling components in the paired cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) EOC cell lines. Our results showed that several negative regulators of Wnt signaling are downregulated, whereas a few Wnt ligands and known Wnt/β-catenin target genes are upregulated in A2780cp cells compared to A2780s cells, suggesting that Wnt/β-catenin signaling is more active in A2780cp cells. Further analysis revealed nuclear localization of β-catenin and higher β-catenin transcriptional activity in A2780cp cells compared to A2780s cells. Finally, we demonstrated that chemical inhibition of β-catenin transcriptional activity by its inhibitor CCT036477 sensitized A2780cp cells to carboplatin, supporting a role for β-catenin in carboplatin resistance in A2780cp cells. In conclusion, our data suggest that increased Wnt/β-catenin signaling activity contributes to carboplatin resistance in A2780cp cells. - Highlights: • Wnt ligands and target genes are upregulated in cisplatin resistant A2780cp cells. • Negative regulators of Wnt signaling are down-regulated in A2780cp cells. • β-catenin transcriptional activity is higher in A2780cp cells compared to A2780s cells. • Inhibition of β-catenin activity increases carboplatin cytotoxicity in A2780cp cells.

  19. Platinum desensitization in patients with carboplatin hypersensitivity: A single-institution retrospective study.

    Science.gov (United States)

    Altwerger, Gary; Gressel, Gregory M; English, Diana P; Nelson, Wendelin K; Carusillo, Nina; Silasi, Dan-Arin; Azodi, Masoud; Santin, Alessandro; Schwartz, Peter E; Ratner, Elena S

    2017-01-01

    The carboplatin desensitization (CD) protocol presented here allows patients with either a positive skin test or a prior hypersensitivity reaction (HSR) to safely, rapidly and effectively continue with carboplatin infusions. Newly described factors can identify patients at risk for developing adverse events during CD. A retrospective review was performed on patients with gynecologic cancer who underwent CD between 2005 and 2014. The CD protocol uses a four-step dilution process over 3.5h. 129 patients underwent CD and completed a total of 788cycles. The desensitization protocol prevented HSRs in 96% (753 out of 788) of these cycles. Patients achieved an average of 6.1cycles (SD±4.55, range 0-23) with CD. The CD protocol allowed 73% (94 of 129) of the patients to undergo carboplatin infusion without reaction. Patients with moderate to life-threatening HSRs (grade 2 through 4) were 10.5years younger at initial CD than patients with grades 0 or 1 HSRs (52.3 vs. 63, P = 0.0307). One patient death occurred during her thirteenth desensitization cycle. The HSR in this case was complicated by pre-exisiting pulmonary hypertension. This is the largest study of its kind showing a safe, effective and rapid (3.5h) CD protocol. The majority of patients with a history of either carboplatin hypersensitivity reaction or a positive skin test completed the CD protocol without HSRs. Age was identified as a risk factor for HSR severity during CD. Age can be employed along with pre-load dependent cardiac conditions as a way to help risk stratify patients undergoing CD. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Expression of drug targets in patients treated with sorafenib, carboplatin and paclitaxel.

    Directory of Open Access Journals (Sweden)

    Lucia B Jilaveanu

    Full Text Available Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP to carboplatin, paclitaxel and placebo (CP.Using a method of automated quantitative analysis (AQUA of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients.An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS and overall survival (OS in our combined cohort (SCP and CP arms. Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR vs. (SD+PD+ un-evaluable.In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen.

  1. Distinct genetic alterations occur in ovarian tumor cells selected for combined resistance to carboplatin and docetaxel

    Directory of Open Access Journals (Sweden)

    Armstrong Stephen R

    2012-11-01

    Full Text Available Abstract Background Current protocols for the treatment of ovarian cancer include combination chemotherapy with a platinating agent and a taxane. However, many patients experience relapse of their cancer and the development of drug resistance is not uncommon, making successful second line therapy difficult to achieve. The objective of this study was to develop and characterize a cell line resistant to both carboplatin and docetaxel (dual drug resistant ovarian cell line and to compare this cell line to cells resistant to either carboplatin or docetaxel. Methods The A2780 epithelial endometrioid ovarian cancer cell line was used to select for isogenic carboplatin, docetaxel and dual drug resistant cell lines. A selection method of gradually increasing drug doses was implemented to avoid clonal selection. Resistance was confirmed using a clonogenic assay. Changes in gene expression associated with the development of drug resistance were determined by microarray analysis. Changes in the expression of selected genes were validated by Quantitative Real-Time Polymerase Chain Reaction (QPCR and immunoblotting. Results Three isogenic cell lines were developed and resistance to each drug or the combination of drugs was confirmed. Development of resistance was accompanied by a reduced growth rate. The microarray and QPCR analyses showed that unique changes in gene expression occurred in the dual drug resistant cell line and that genes known to be involved in resistance could be identified in all cell lines. Conclusions Ovarian tumor cells can acquire resistance to both carboplatin and docetaxel when selected in the presence of both agents. Distinct changes in gene expression occur in the dual resistant cell line indicating that dual resistance is not a simple combination of the changes observed in cell lines exhibiting single agent resistance.

  2. Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

    OpenAIRE

    2016-01-01

    Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite...

  3. Economic explanations for concurrent sourcing

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    2010-01-01

    Concurrent sourcing is a phenomenon where firms simultaneously make and buy the same good, i.e. they simultaneously use the governance modes of market and hierarchy. Though concurrent sourcing seems to be widespread, few studies of sourcing have focused on this phenomenon. This paper reviews diff...... different economic explanations for why firms use concurrent sourcing. The distinctive features of the explanations are compared, and it is discussed how they may serve as a springboard for research on concurrent sourcing. Managerial implications are also offered....

  4. Intraperitoneal chemotherapy in the management of ovarian cancer: focus on carboplatin

    Directory of Open Access Journals (Sweden)

    Maurie Markman

    2009-02-01

    Full Text Available Maurie MarkmanUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USAAbstract: Both pre-clinical studies and phase 1–2 clinical trials have provided strong support for the potential role of regional drug delivery in the management of epithelial ovarian cancer, a disease process whose major manifestations remain largely localized to the peritoneal cavity in the majority of individuals with this malignancy. The results of 3 phase 3 randomized trials have revealed the favorable impact of primary cisplatin-based intraperitoneal chemotherapy in women who initiate drug treatment with small-volume residual ovarian cancer following an attempt at optimal surgical cytoreduction. Concerns have been raised regarding the toxicity of regional treatment, particularly the side-effect profile associated with cisplatin. One rational approach to improving the tolerability of intraperitoneal chemotherapy is to substitute carboplatin for cisplatin. This review discusses the rationale for and data supporting regional treatment of epithelial ovarian cancer, and highlights the potential role for intraperitoneal carboplatin in this clinical setting.Keywords: ovarian cancer, intraperitoneal chemotherapy, cisplatin, carboplatin

  5. Unilateral Optic Disc Papilloedema following Administration of Carboplatin Chemotherapy for Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Philippa Lewis

    2014-01-01

    Full Text Available A 48-year-old woman with a positive BRCA1 gene mutation was diagnosed with stage 3b high-grade ovarian endometrioid carcinoma. She was treated with adjuvant carboplatin at a dose of 740 mg (AUC 6 in 3-weekly cycles. Five days after her fifth cycle of carboplatin, she awoke with new-onset blurred vision in her left eye. An ophthalmology review showed left-sided disc oedema with normal optic nerve function tests and 6/24 visual acuity. A CT scan of the head and orbits was performed which showed no evidence of metastasis or raised intracranial pressure. An autoimmune screen was performed which did not reveal any explanation for her visual symptoms. Fundus fluorescein angiography showed bilateral intense late disc leakage with no evidence of vasculitis. Her chemotherapy was stopped in view of a radiological and biochemical remission and her visual symptoms were monitored. She was also started on a tapering dose of prednisolone 40 mg daily. Five months after the initial review, she has developed left optic disc atrophy with 6/18 visual acuity, while the right eye remains asymptomatic. The diagnosis was felt to be that of carboplatin-induced unilateral disc oedema, a very rare side effect of this chemotherapy.

  6. Continuous intraperitoneal carboplatin delivery for the treatment of late-stage ovarian cancer.

    Science.gov (United States)

    Zhidkov, Nickholas; De Souza, Raquel; Ghassemi, Amir H; Allen, Christine; Piquette-Miller, Micheline

    2013-09-01

    The rate of failure of chemotherapy treatment in ovarian cancer remains high, resulting in a low 5-year survival rate of 20-40% in patients that present with advanced-stage disease. Treatment-free periods between cycles of chemotherapy may contribute to accelerated tumor cell proliferation and decreased treatment response. The elimination of treatment-free breaks has been deemed beneficial in the context of cell-cycle-specific agents. The potential benefit of this approach for non-cell-cycle-specific agents has not yet been elucidated. The present study is the first to address this issue by investigating the impact of continuous versus intermittent intraperitoneal administration of carboplatin over a 14 day period to SCID mice bearing SKOV-3 ovarian cancer xenografts. Immunostaining of tumor sections was employed to quantify tumor proliferation, angiogenesis, and apoptosis using Ki-67, CD-31, caspase-3 (CASP3), and terminal deoxytransferase-mediated dUTP nick-end labeling (TUNEL). Continuous ip administration of carboplatin resulted in greater tumor growth inhibition than intermittent therapy (p < 0.05). Significantly greater tumor cell apoptosis and less cell proliferation and angiogenesis were measured in tumors of mice treated with continuous carboplatin as compared to both intermittent and control groups. These results indicate that continuous local administration may be a promising approach to improve the effectiveness of platinum-based chemotherapy regimens.

  7. nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma

    Directory of Open Access Journals (Sweden)

    Go Makimoto

    2014-01-01

    Full Text Available We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

  8. nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma

    Science.gov (United States)

    Makimoto, Go; Fujiwara, Keiichi; Watanabe, Hiromi; Kameyama, Nobuhisa; Matsushita, Mizuho; Rai, Kammei; Sato, Ken; Yonei, Toshiro; Sato, Toshio; Shibayama, Takuo

    2014-01-01

    We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF) injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma. PMID:24575009

  9. Efficacy of carboplatin-based preoperative chemotherapy for triple-negative breast cancer. A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Li-Yang; Xie, Hua; Zhou, Hang; Yao, Wen-Xiu; Zhao, Xin; Wang, Yi

    2017-01-01

    To evaluate the efficacy and safety of carboplatin-based preoperative chemotherapy in triple-negative breast cancer patients (TNBC). PubMed, EMBASE, the Web of Science, the Cochrane Library, major clinical trial registries, and abstract collections from major international meetings were systematically searched for relevant randomized controlled trials. Endpoints included rates of pathologic complete response (pCR), overall response (ORR), breast-conserving surgery (BCS) and toxicity. Pooled relative risk (RR) was calculated for each endpoint using a fixed- or random-effect model depending on the heterogeneity among included studies. A total of 5 randomized controlled trials involving 1007 patients were included in the meta-analysis. Carboplatin-based chemotherapy was associated with a pooled pCR rate of 53.3%, which was significantly higher than the rate associated with non-carboplatin therapy (37.8%, RR: 1.41, 95% confidence interval [CI]: 1.23 to 1.62, p less than 0.00001). Compared with non-carboplatin therapy (48.1%), carboplatin-based chemotherapy increased BCS rate (59.7%, RR: 1.24, 95%CI: 1.06 to 1.46, p=0.007). Carboplatin-based chemotherapy was associated with similar ORR as non-carboplatin therapy. Carboplatin-based chemotherapy was associated with higher incidence of grade 3 or 4 anemia, neutropenia, febrile neutropenia, and thrombocytopenia than non-carboplatin therapy, while the 2 regimens were associated with similar incidence of fatigue, leucopenia, and nausea/vomiting. The available evidence suggests that carboplatin-based preoperative chemotherapy is associated with significantly better pCR and BCS rates than non-carboplatin-based therapy in TNBC patients.

  10. CRDTs: Consistency without concurrency control

    CERN Document Server

    Letia, Mihai; Shapiro, Marc

    2009-01-01

    A CRDT is a data type whose operations commute when they are concurrent. Replicas of a CRDT eventually converge without any complex concurrency control. As an existence proof, we exhibit a non-trivial CRDT: a shared edit buffer called Treedoc. We outline the design, implementation and performance of Treedoc. We discuss how the CRDT concept can be generalised, and its limitations.

  11. A Lower Bound on Concurrence

    Institute of Scientific and Technical Information of China (English)

    LIU Li-Guo; TIAN Cheng-Lin; CHEN Ping-Xing; YUAN Nai-Chang

    2009-01-01

    We derive an analytical lower bound on the concurrence for bipartite quantum systems with an improved computable cross norm or realignment criterion and an improved positive partial transpose criterion respectively.Furthermore we demonstrate that our bound is better than that obtained from the local uncertainty relations criterion with optimal local orthogonal observables which is known as one of the best estimations of concurrence.

  12. Concurrent Validity and Holland's Theory

    Science.gov (United States)

    Gaffey, Robert L.; Walsh, W. Bruce

    1974-01-01

    This study was designed to explore two areas: (1) the concurrent validity of Holland's theory for employed men using four different operational definitions of vocational orientation, and (2) the relationships among all possible combinations of same named scales across the four inventories. Findings tend to support the concurrent validity of…

  13. Concurrent Validity and Holland's Theory

    Science.gov (United States)

    Gaffey, Robert L.; Walsh, W. Bruce

    1974-01-01

    This study was designed to explore two areas: (1) the concurrent validity of Holland's theory for employed men using four different operational definitions of vocational orientation, and (2) the relationships among all possible combinations of same named scales across the four inventories. Findings tend to support the concurrent validity of…

  14. Partnership concurrency and coital frequency.

    Science.gov (United States)

    Gaydosh, Lauren; Reniers, Georges; Helleringer, Stéphane

    2013-09-01

    National HIV prevalence estimates across sub-Saharan Africa range from less than 1 percent to over 25 percent. Recent research proposes several explanations for the observed variation, including prevalence of male circumcision, levels of condom use, presence of other sexually transmitted infections, and practice of multiple concurrent partnerships. However, the importance of partnership concurrency for HIV transmission may depend on how it affects coital frequency with each partner. The coital dilution hypothesis suggests that coital frequency within a partnership declines with the addition of concurrent partners. Using sexual behavior data from rural Malawi and urban Kenya, we investigate the relationship between partnership concurrency and coital frequency, and find partial support for the coital dilution hypothesis. We conclude the paper with a discussion of our findings in light of the current literature on concurrency.

  15. DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells

    Directory of Open Access Journals (Sweden)

    de Wilde Rudy L

    2009-10-01

    Full Text Available Abstract Background The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics. Methods DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA hydrolysis assay. Results While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin. In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692, or did not exist for gemcitabine. Conclusion The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.

  16. Comparison of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with mitomycin or carboplatin for diffuse malignant peritoneal mesothelioma.

    Science.gov (United States)

    Shetty, Shreya J; Bathla, Lokesh; Govindarajan, Venkatesh; Thomas, Peter; Loggie, Brian W

    2014-04-01

    Diffuse malignant peritoneal mesothelioma is a rare, aggressive disease. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved outcomes where systemic chemotherapy has not succeeded. In this study, we compare outcomes of patients treated with mitomycin or carboplatin as perfusate. In this retrospective study, 47 procedures (CRS + HIPEC) were conducted on 44 patients between March 2003 and August 2010 with either mitomycin or carboplatin. χ(2) and Student's t test were used for comparison of clinicopathological variables and Kaplan-Meier curves and log rank test were used to compare overall survival. Median survival of the mitomycin group was 18 months with 1- and 5-year survivals of 72.3 and 27.3 per cent, respectively. Median survival of the carboplatin group was not reached and 1- and 5-year survivals were 89.7 and 62.5 per cent, respectively (P = 0.014). Mean hospital and intensive care unit length of stay was 18.9 and 8.7 days in the mitomycin group and 12.5 and 2.3 days in the carboplatin group (P = 0.0069). Mean number of packed red blood cell units transfused was higher in the mitomycin group compared with the carboplatin group (3.54 vs 0.83, P mitomycin.

  17. Modulation of MDR1 and MRP3 gene expression in lung cancer cells after paclitaxel and carboplatin exposure.

    Science.gov (United States)

    Melguizo, Consolación; Prados, Jose; Luque, Raquel; Ortiz, Raúl; Caba, Octavio; Alvarez, Pablo J; Gonzalez, Beatriz; Aranega, Antonia

    2012-12-05

    Carboplatin-paclitaxel is a reference regimen in the treatment of locally advanced or disseminated non-small cell lung cancer (NSCLC). This paper discusses the multidrug resistance developed with this drug combination, which is one of the major obstacles to successful treatment. In order to understand and overcome the drug resistance pattern of NSCLC after carboplatin plus paclitaxel exposure, levels of mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein 3 (MRP3) were investigated in primary NSCLC cell lines (A-549 and A-427) and a metastasis-derived NSCLC cell line (NODO). Our results showed that exposure of the three NSCLC lines to plasma concentrations of paclitaxel (5 μM) produced an increase in MDR1 expression, while MRP3 showed no alteration in expression. By contrast, the same cells exposed to carboplatin plasma concentrations (30 μM) showed overexpression of MRP3. In these cells, MDR1 showed no expression changes. Interestingly, the combination of both paclitaxel and carboplatin caused increased expression of the MDR1 drug resistance gene rather than the individual treatments. These results suggest that carboplatin and paclitaxel may induce drug resistance mediated by MDR1 and MRP3, which may be enhanced by the simultaneous use of both drugs.

  18. Modulation of MDR1 and MRP3 Gene Expression in Lung Cancer Cells after Paclitaxel and Carboplatin Exposure

    Directory of Open Access Journals (Sweden)

    Consolación Melguizo

    2012-12-01

    Full Text Available Carboplatin-paclitaxel is a reference regimen in the treatment of locally advanced or disseminated non-small cell lung cancer (NSCLC. This paper discusses the multidrug resistance developed with this drug combination, which is one of the major obstacles to successful treatment. In order to understand and overcome the drug resistance pattern of NSCLC after carboplatin plus paclitaxel exposure, levels of mRNA expression of multidrug resistance 1 (MDR1 and multidrug resistance-associated protein 3 (MRP3 were investigated in primary NSCLC cell lines (A-549 and A-427 and a metastasis-derived NSCLC cell line (NODO. Our results showed that exposure of the three NSCLC lines to plasma concentrations of paclitaxel (5 μM produced an increase in MDR1 expression, while MRP3 showed no alteration in expression. By contrast, the same cells exposed to carboplatin plasma concentrations (30 μM showed overexpression of MRP3. In these cells, MDR1 showed no expression changes. Interestingly, the combination of both paclitaxel and carboplatin caused increased expression of the MDR1 drug resistance gene rather than the individual treatments. These results suggest that carboplatin and paclitaxel may induce drug resistance mediated by MDR1 and MRP3, which may be enhanced by the simultaneous use of both drugs.

  19. CONTINUOUS CARBOPLATIN INFUSION DURING 6 WEEKS RADIOTHERAPY IN LOCALLY INOPERABLE NON-SMALL-CELL LUNG-CANCER - A PHASE-I AND PHARMACOKINETIC STUDY

    NARCIS (Netherlands)

    GROEN, HJM; VANDERLEEST, AHD; DEVRIES, EGE; UGES, DRA; SZABO, BG; MULDER, NH

    1995-01-01

    A phase I study was performed in 21 patients with previously untreated, locally inoperable, non-small-cell lung cancer (NSCLC) with ambulatory continuous carboplatin infusion together with continuous thoracic irradiation over 6 weeks. A dose range for carboplatin of 15 mg m(-2) day(-1) during the la

  20. Concurrent chemoradiotherapy for patients with postoperative recurrence of surgically resected non-small-cell lung cancer.

    Science.gov (United States)

    Takenaka, Tomoyoshi; Takenoyama, Mitsuhiro; Toyozawa, Ryo; Inamasu, Eiko; Yoshida, Tsukihisa; Toyokawa, Gouji; Shiraishi, Yoshimasa; Hirai, Fumihiko; Yamaguchi, Masafumi; Seto, Takashi; Ichinose, Yukito

    2015-01-01

    A few reports have evaluated the outcomes of concurrent chemoradiotherapy (CRT) for patients with postoperative recurrence of non-small cell lung cancer (NSCLC). From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of those, 280 patients had experienced postoperative recurrence by the end of 2012. Thirty-five patients received concurrent CRT as initial treatment of the recurrent disease. We retrospectively reviewed these cases, analyzed the outcomes of concurrent CRT after surgical resection, and examined the factors that predict long-term postrecurrence survival. The most common sites of recurrence in this cohort were the lymph nodes in 24 patients, followed by the lung in 5 patients and bone in 6 patients. The median radiation dose given as the initial treatment of recurrence was 60 Gy (range, 30-60 Gy). Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered in 23 cases, and a carboplatin-based chemotherapy regimen was administered in 12. The median progression-free and postrecurrence survival after CRT was 13 months (range, 4-127 months) and 31 months (range, 5-127 months), respectively. Seven patients were still alive without evidence of disease for > 3 years after the recurrence diagnosis. The ECOG performance status (PS), surgical procedure, and types of platinum agents used were independent prognostic factors for postrecurrence survival. Concurrent CRT for recurrent NSCLC is a promising therapy for selected patients. A poor PS and postpneumonectomy state were poor prognostic factors for patients who received concurrent CRT. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

    Science.gov (United States)

    González-Martín, A J; Calvo, E; Bover, I; Rubio, M J; Arcusa, A; Casado, A; Ojeda, B; Balañá, C; Martínez, E; Herrero, A; Pardo, B; Adrover, E; Rifá, J; Godes, M J; Moyano, A; Cervantes, A

    2005-05-01

    The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

  2. New methods of concurrent checking

    CERN Document Server

    Goessel, Michael; Sogomonyan, Egor; Marienfeld, Daniel

    2008-01-01

    Written by a team of two leading experts and two very successful young former PhD students, New Methods of Concurrent Checking describes new methods of concurrent checking, such as partial duplication, use of output dependencies, complementary circuits, self-dual parity, self-dual duplication and others. A special chapter demonstrates how the new general methods of concurrent checking can be more specifically applied to regular structures to obtain optimum results. This is exemplified for all types of adders up to 64 bits with a level of detail never before presented in the literature. The cle

  3. Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib.

    Science.gov (United States)

    de Vos, J; Ramos Vega, S; Noorman, E; de Vos, P

    2012-09-01

    In human medicine, primary frontal sinus squamous cell carcinoma (pFS-SCC) is not frequently reported. In veterinary medicine, frontal sinus SCC is exclusively described as an extension of nasal cavity SCC. To our knowledge, this is the first publication concerning canine pFS-SCC, diagnosed using histology or cytology and medical imaging, in three dogs. The tumours extended into the orbit or brain cavity, without nasal involvement. Treatment was initiated with piroxicam-carboplatin. Prolongation of carboplatin delivery with a low dose intensity was performed on dogs with a favourable initial response. Dog 1 achieved a complete remission (CR), but was euthanized 344 days after start of therapy. Dog 2, still alive 3 years after start of therapy and in CR, received 14 carboplatin deliveries. In dog 3, after changing the treatment protocol into piroxicam-toceranib, a significant tumour reduction occurred, but the dog was euthanized after 195 days because of a relapse.

  4. EFFECT OF NEOADJUVANT CHEMOTHERAPY USING PACLITAXEL COMBINED WITH CARBOPLATIN ON ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    XIONG Hong-chao; CHEN Jin-feng; ZHANG Li-jian

    2006-01-01

    Objective: To assess the therapeutic effectiveness of preoperative neoadjuvant chemotherapy using a combination of paclitaxel and carboplatin on local advanced non-small cell lung cancer (NSCLC). Methods: Twenty-five patients with advanced NSCLC were treated with paclitaxel and carboplatin for 2 to 4 cycles before undergoing tumor resection and then postoperative chemotherapy/radiotherapy therapy for 2 to 4 cycles. Results: Following neoadjuvant chemotherapy, the most prominent side-effect was bone marrow restraint. The overall response rate of preoperative chemotherapy was 56%. The mean survival time was 26.5 months, with 1-, 2- and 5-year survival rates of 55%, 25%, and 16%, respectively. All NSCLC patients survived the perioperative period. Conclusion: Preoperative neoadjuvant chemotherapy combining paclitaxel and carboplatin produced minimal side-effect while increasing the probability that advanced NSCLC patients would be able to undergo surgery thus improving their prognosis.

  5. A CAD MODEL FOR FUZZY CONCURRENT TOLERANCE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Research situation of concurrent tolerance design has been analyzed. As fuzzy factors are objective and unavoidable in concurrent tolerance design, fuzzy optimization theory is applied in the design. A new mathematical model of concurrent tolerance design is constructed.

  6. A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients.

    Science.gov (United States)

    Schmitt, Antonin; Gladieff, Laurence; Lansiaux, Amélie; Bobin-Dubigeon, Christine; Etienne-Grimaldi, Marie-Christine; Boisdron-Celle, Michèle; Serre-Debauvais, Françoise; Pinguet, Frédéric; Floquet, Anne; Billaud, Eliane; Le Guellec, Chantal; Penel, Nicolas; Campone, Mario; Largillier, Rémy; Capitain, Olivier; Fabbro, Michel; Houede, Nadine; Medioni, Jacques; Bougnoux, Philippe; Lochon, Isabelle; Chatelut, Etienne

    2009-05-15

    It has recently been shown that it is possible to improve the prediction of carboplatin clearance by adding plasma cystatin C level (cysC), an endogenous marker of glomerular filtration rate, to the other patient characteristics routinely used for carboplatin individual dosing, namely serum creatinine (Scr), actual body weight (ABW), age, and sex. This multicenter pharmacokinetic study was done to evaluate prospectively the benefit of using cysC for carboplatin individual dosing. The 357 patients included in the study were receiving carboplatin as part of established protocols. A population pharmacokinetic analysis was done using NONMEM program. Seven covariates studied were as follows: Scr, cysC, age, sex, ABW, ideal body weight, and lean body mass. The best covariate equation was as follows: carboplatin clearance (mL/min) = 117.8. (Scr/75)(-0.450). (cysC/1,00)(-0.385). (ABW/65)(+0.504). (age/56)(-0.366). 0.847(sex), with Scr in micromol/L, cysC in mg/L, ABW in kilograms, age in years, and sex = 0 for male. Using an alternative weight descriptor (ideal body weight or lean body mass) did not improve the prediction. This final covariate model was validated by bootstrap analysis. The bias (mean percentage error) and imprecision (mean absolute percentage error) were +1% and 15%, respectively, on the total population, and were of a similar magnitude in each of the three subgroups of patients defined according to their body mass index. For the first time, a unique formula is proposed for carboplatin individual dosing to patients, which is shown to be equally valid for underweight, normal weight, and obese patients.

  7. Outcome of Men With Relapse After Adjuvant Carboplatin for Clinical Stage I Seminoma.

    Science.gov (United States)

    Fischer, Stefanie; Tandstad, Torgrim; Wheater, Matthew; Porfiri, Emilio; Fléchon, Aude; Aparicio, Jorge; Klingbiel, Dirk; Skrbinc, Breda; Basso, Umberto; Shamash, Jonathan; Lorch, Anja; Dieckmann, Klaus-Peter; Cohn-Cedermark, Gabriella; Ståhl, Olof; Chau, Caroline; Arriola, Edurne; Marti, Kalena; Hutton, Paul; Laguerre, Brigitte; Maroto, Pablo; Beyer, Jörg; Gillessen, Silke

    2017-01-10

    Purpose Adjuvant carboplatin is one of three management strategies that may follow inguinal orchiectomy in clinical stage I seminoma. However, little is known about the outcome of patients who experience a relapse after such treatment. Patients and Methods Data from 185 patients who relapsed after adjuvant carboplatin between January 1987 and August 2013 at 31 centers/groups from 20 countries were collected and retrospectively analyzed. Primary outcomes were disease-free survival and overall survival. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results With a median follow-up of 53 months (95% CI, 48 to 60 months) the 5-year disease-free survival was 82% (95% CI, 77% to 89%), and the 5-year overall survival was 98% (95% CI, 95% to 100%). The median time from orchiectomy to relapse was 19 months (95% CI, 17 to 23 months); 15% (95% CI, 10% to 21%) of relapses occurred > 3 years after treatment. The majority of relapses were detected by computed tomography scan during routine follow-up, 98% in the International Germ Cell Cancer Collaborative Group good prognosis group. Chemotherapy was administered to 92% of patients, mostly as standard first-line treatment corresponding to stage; 8% of patients had additional local treatments. Only 28 patients experienced a second relapse. At last follow-up, 174 (94%) of 185 patients were alive without disease, and four patients with disease. Seven patients died, three of whom due to progressive disease. Conclusion Within the limitations of a retrospective analysis, the results suggest that the majority of patients who experience a relapse after adjuvant carboplatin for clinical stage I seminoma can be successfully treated with a cisplatin-based chemotherapy regimen adequate for stage. Because 15% of the relapses occurred > 3 years after adjuvant treatment, a minimum of 5 years follow-up is recommended.

  8. A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium

    Directory of Open Access Journals (Sweden)

    Qian Jiong

    2007-06-01

    Full Text Available Abstract Background Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium. Methods Patients with advanced TCC were treated with gemcitabine 1200 mg/m2 on days 1 and 8 and carboplatin area under the concentration-time curve(AUC 5 on day 1 every 21 days. Results Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1–6 was administered. Overall response rate was 46.2% (95% confidence interval: 32–65% including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6–8.4 months and 13.6 months (95% confidence interval: 10.2–17.0 months, respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4% patients. Conclusion The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens. Trial registration ISRCTN88259320

  9. Reference Capabilities for Concurrency Control

    OpenAIRE

    Castegren, Elias; Wrigstad, Tobias

    2016-01-01

    The proliferation of shared mutable state in object-oriented programming complicates software development as two seemingly unrelated operations may interact via an alias and produce unexpected results. In concurrent programming this manifests itself as data-races. Concurrent object-oriented programming further suffers from the fact that code that warrants synchronisation cannot easily be distinguished from code that does not. The burden is placed solely on the programmer to reason ab...

  10. Concurrent engineering: effective deployment strategies

    Directory of Open Access Journals (Sweden)

    Unny Menon

    1996-12-01

    Full Text Available This paper provides a comprehensive insight into current trends and developments in Concurrent Engineering for integrated development of products and processes with the goal of completing the entire cycle in a shorter time, at lower overall cost and with fewer engineering design changes after product release. The evolution and definition of Concurrent Engineering are addressed first, followed by a concise review of the following elements of the concurrent engineering approach to product development: Concept Development: The Front-End Process, identifying Customer Needs and Quality Function Deployment, Establishing Product Specifications, Concept Selection, Product Architecture, Design for Manufacturing, Effective Rapid Prototyping, and The Economics of Product Development. An outline of a computer-based tutorial developed by the authors and other graduate students funded by NASA ( accessible via the world-wide-web . is provided in this paper. A brief discussion of teamwork for successful concurrent engineering is included, t'ase histories of concurrent engineering implementation at North American and European companies are outlined with references to textbooks authored by Professor Menon and other writers. A comprehensive bibliography on concurrent engineering is included in the paper.

  11. nab-Paclitaxel in Combination with Carboplatin for a Previously Treated Thymic Carcinoma

    OpenAIRE

    Go Makimoto; Keiichi Fujiwara; Hiromi Watanabe; Nobuhisa Kameyama; Mizuho Matsushita; Kammei Rai; Ken Sato; Toshiro Yonei; Toshio Sato; Takuo Shibayama

    2014-01-01

    We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fr...

  12. Successful treatment with pemetrexed, Carboplatin, and bevacizumab for platinum-resistant adenocarcinoma of the lung.

    Science.gov (United States)

    Wada, Sae; Fujimoto, Nobukazu; Gemba, Kenichi; Asano, Michiko; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kishimoto, Takumi

    2012-01-01

    WE PRESENT TWO CASES OF RELAPSED ADENOCARCINOMA OF THE LUNG: a 50-year-old male and a 67-year-old male. Both patients had previously been treated with platinum-containing systemic chemotherapy. In both cases, significant clinical efficacy was demonstrated with combination chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab as salvage treatment. Adverse events were mild. This regimen might be a viable therapeutic option even after heavy treatment such as platinum-containing chemotherapy, especially for patients with preserved organ function and good performance status.

  13. Successful Treatment with Pemetrexed, Carboplatin, and Bevacizumab for Platinum-Resistant Adenocarcinoma of the Lung

    Directory of Open Access Journals (Sweden)

    Sae Wada

    2012-01-01

    Full Text Available We present two cases of relapsed adenocarcinoma of the lung: a 50-year-old male and a 67-year-old male. Both patients had previously been treated with platinum-containing systemic chemotherapy. In both cases, significant clinical efficacy was demonstrated with combination chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab as salvage treatment. Adverse events were mild. This regimen might be a viable therapeutic option even after heavy treatment such as platinum-containing chemotherapy, especially for patients with preserved organ function and good performance status.

  14. Comparative evaluation of cisplatin and carboplatin sensitivity in endometrial adenocarcinoma cell lines.

    OpenAIRE

    Rantanen, V; Grénman, S.; Kulmala, J; Grénman, R

    1994-01-01

    Platinum analogues are frequently used in the treatment of advanced or recurrent endometrial cancer. To study the sensitivity of endometrial cancer to cisplatin and carboplatin, we tested two long-established (RL95-2, KLE) and six new cell lines (UM-EC-1, UM-EC-2, UM-EC-3, UT-EC-2A, UT-EC-2B, UT-EC-3) using the 96-well-plate clonogenic assay. This assay has proven to be suitable for testing chemosensitivity of both adenocarcinoma and squamous cell carcinoma. The chemosensitivity was expressed...

  15. 子宫颈癌患者子宫动脉插管与静脉全身化疗两种途径新辅助化疗的效果对比%Comparison of effectiveness between intra-arterial and intra-venous neoadjuvant chemotherapy in stage Ⅰb2-Ⅱ b cervical carcinoma

    Institute of Scientific and Technical Information of China (English)

    曹冬焱; 杨佳欣; 沈铿; 向阳; 潘凌亚; 郎景和; 吴鸣; 黄惠芳

    2008-01-01

    Objective To compare the effect between intra-arterial and intra-venous neoadjuvant chemotherapy(NACT)in stage Ⅰb2-Ⅱ b cervical carcinoma.Methods A retrospective analysis Was done on 52 cases of intra-venous NACT and 95 eases of intm-arterial NACT for stage Ⅰ b2-Ⅱ b cervical carcinoma treatad in Peking Union Medical College Hospital from 1999.ResulIs The response rate of intraveHous NACT and intra-arterial NACT was 88%(46/52)and 79%(75/95).and the operative rate after NACT Was 81%(42/52)and 72%(68/95)respectively(P>0.05).There were no significant differences in surgery time,blood loss and pest-operative morbidity between these two groups.Pathological parametrial positive rate after NACT in arterial group(6%)Was significantly lower than that of venous group (50%,P>0.05).The venous group had very similar recurrence rates(13%vs 17%)and death rates (9%VS 12%)when compared with the arterial group(P>0.05).Conclusions The intra-arterial and intra-venous NACT for stage Ⅰ b2-Ⅱb cervical carcinoma show similar response rate.operative rate and surgical difficulties.Arterial NACT shows a better effect on parametrial infiltration.%目的 比较不同途径新辅助化疗对Ⅰ b2~Ⅱ b期官颈癌的疗效.方法 对北京协和医院1999年以来收治的147例Ⅰ b2~Ⅱ b期行新辅助化疗的宫颈癌患者的临床病理资料进行同顾性分析,其中,经静脉全身化疗者(静脉组)52例,经子宫动脉插管化疗者(动脉组)95例.结果 静脉组患者经新辅助化疗后总反应率为88%(46/52),动脉组为79%(75/95),两组比较,差异无统计学意义(P>0.05).静脉组患者新辅助化疗后可手术率为81%(42/52),动脉组为72%(68/95),两组比较,差异无统计学意义(P>0.05).两组患者新辅助化疗后手术时间、出血量和并发症发生率相近.Ⅱ b期患者经新辅助化疗后手术,术后病理检查发现官旁仍有肿瘤浸润者动脉组显著低于静脉组(分别为6%、50%,P0.05)分别比较,

  16. Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Songliang ZHANG

    2015-06-01

    Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

  17. Vaginal delivery of carboplatin-loaded thermosensitive hydrogel to prevent local cervical cancer recurrence in mice.

    Science.gov (United States)

    Wang, Xue; Wang, Jin; Wu, Wenbin; Li, Hongjun

    2016-11-01

    Local tumor recurrence after cervical cancer surgery remains a clinical problem. Vaginal delivery of thermosensitive hydrogel may be suited to reduce tumor relapse rate with more efficacy and safety. A pilot study was carried out to evaluate the efficacy of carboplatin-loaded poloxamer hydrogel to prevent local recurrence of cervical cancer after surgery. In vivo vaginal retention evaluation of 27% poloxamer hydrogel in mice was proven to be a suitable vaginal drug delivery formulation due to its low gelation temperature. A mimic orthotopic cervical/vaginal cancer recurrence model after surgery was established by injecting murine cervical cancer cell line U14 into the vaginal submucosa to simulate the residual tumor cells infiltrated in the surgical site, followed by drug administration 24 h later to interfere with the formation/recurrence of the tumor. By infusing fluorescein sodium-loaded hydrogel into the vagina of mice, a maximized accumulation of fluorescein sodium (Flu) in the vagina was achieved and few signals were observed in other organs. When used in the prevention of the cervical cancer formation/recurrence in mice, the carboplatin-loaded poloxamer hydrogel exhibited great efficacy and systemic safety. In conclusion, thermosensitive hydrogel presents a simple, practical approach for the local drug delivery via vagina against cervical cancer recurrence.

  18. Managing Complexity of Control Software through Concurrency

    NARCIS (Netherlands)

    Hilderink, G.H.

    2005-01-01

    In this thesis, we are concerned with the development of concurrent software for embedded systems. The emphasis is on the development of control software. Embedded systems are concurrent systems whereby hardware and software communicate with the concurrent world. Concurrency is essential, which

  19. The incidence of ototoxicity in child malignancy cases that received carboplatin therapy with otoacoustic emission (OAE) examination

    Science.gov (United States)

    Wibowo, J. K.; Zizlavsky, S.; Suwento, R.; Sjakti, H. A.; Prihartono, J.

    2017-08-01

    Malignancy is a significant public health problem, both globally and in Indonesia. Chemotherapy is one of the modality in malignancy cases. Carboplatin (cis-diammine-cyclobutanedi-carboxylato platinum) is a second-generation platinum compound that has often been used in the management of cases of malignancies. On the other hand, side effects of cytotoxic drugs need to be considered, especially ototoxic effects. Ototoxicity is dysfunction and damage to the structure of the inner ear that has been caused by drugs or other certain chemicals. The aim of this study is to assess ototoxic effects due to the influence of carboplatin in the cases of children with malignancy. This study uses a serial cross-sectional design to evaluate otoacoustic emission (OAE) signal-to-noise ratio (SNR) change as a result of ototoxic effects and risk factors due to the use of ototoxic carboplatin in the Division of Hematology-Oncology of the Department of Pediatrics at Cipto Mangunkusumo General Hospital in Jakarta, where two of 52 studies’ subjects experienced ototoxicity. In the group were receiving chemotherapy, two (5%) of the 40 subjects has experienced ototoxic events characterized by SNR values less than six, whereas SNR values were not less than six in the group that had not received chemotherapy. Risk factors such as gender, age, carboplatin dose, and cycles of chemotherapy did not have a statistically significant relationship to ototoxity.

  20. Exploring binding affinity of oxaliplatin and carboplatin, to nucleoprotein structure of chromatin: spectroscopic study and histone proteins as a target.

    Science.gov (United States)

    Soori, Hosna; Rabbani-Chadegani, Azra; Davoodi, Jamshid

    2015-01-07

    Platinum drugs are potent chemotherapeutic agents widely used in cancer therapy. They exert their biological activity by binding to DNA, producing DNA adducts; however, in the cell nucleus, DNA is complexed with histone proteins into a nucleoprotein structure known as chromatin. The aim of this study was to explore the binding affinity of oxaliplatin and carboplatin to chromatin using spectroscopic as well as thermal denaturation and equilibrium dialysis techniques. The results showed that the drugs quenched with chromophores of chromatin and the quenching effect for oxaliplatin (Ksv = 3.156) was higher than carboplatin (Ksv = 0.28). The binding of the drugs exhibited hypochromicity both in thermal denaturation profiles and UV absorbance at 210 nm. The binding was positive cooperation with spontaneous reaction and oxaliplatin (Ka = 5.3 × 10(3) M(-1), n = 1.7) exhibited higher binding constant and number of binding sites than carboplatin (Ka = 0.33 × 10(3) M(-1), n = 1.0) upon binding to chromatin. Also secondary structure of chromatin proteins was altered upon drugs binding. It is concluded that oxaliplatin represents higher binding affinity to chromatin compared to carboplatin. In chromatin where DNA is compacted into nucleosomes structure with histones, the affinity of the platinated drugs is reduced and histone proteins may play a fundamental role in this binding process. Copyright © 2014. Published by Elsevier Masson SAS.

  1. Carboplatin- and cisplatin-induced potentiation of moderate-dose radiation cytotoxicity in human lung cancer cell lines

    NARCIS (Netherlands)

    Groen, H. J.; Sleijfer, S.; Meijer, C.; Kampinga, H. H.; Konings, A. W. T.; de Vries, E. G. E.; Mulder, N. H.

    1995-01-01

    The interaction between moderate-dose radiation and cisplatin or carboplatin was studied in a cisplatin-sensitive (GLC(4)) and -resistant (GLC(4)-CDDP) human small-cell lung cancer cell line. Cellular toxicity was analysed under oxic conditions with the microculture tetrazolium assay. For the

  2. Effect of gemcitabine heat perfusion chemotherapy combined with carboplatin chemotherapy embolization on serum indexes in patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Wei Zhou; Xing-Yuan Wang; Kun Zhou

    2015-01-01

    Objective:To study the effects of Gemcitabine heat perfusion chemotherapy combined with carboplatin chemotherapy embolization on serum indexes in patients with hepatocellular carcinoma.Methods:90 cases of hepatocellular carcinoma patients were enrolled and randomly divided into two groups. Observation group received gemcitabine heat perfusion chemotherapy combined with carboplatin chemotherapy embolization, control group received gemcitabine conventional perfusion chemotherapy combined with carboplatin chemotherapy embolization. Malignant biological indicators of serum and liver tissue apoptosis regulation of gene expression of the two groups were compared.Results: (1) Serum malignant biological indicators: serum DKK1, TK1, HIF-1 alpha mRNA and protein content of the observation group were lower than that of the control group; (2) Promoting apoptosis gene: MTS1 in liver tissue, Caspase 3 and Bax mRNA and protein contents of the observation group was higher than that of the control group; (3) Apoptosis suppressor genes: liver cancer tissues Plk1, Bcl - 2 and Survivn mRNA and protein contents of the observation group was higher than that of the control group.Conclusion:Gemcitabine hot perfusion chemotherapy plus carboplatin chemotherapy embolism helps to inhibit tumor biological behavior, induce liver cancer cells apoptosis, and it is an ideal treatment for primary liver cancer.

  3. Concurrent Engineering Research and Application

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Research and application of Concurrent Engineering have produced good results. A Chinese style concurrent engineering architecture and reference mode has been produced. A series of break thoughts in BPR (Business Process Reengineering) have been made with organization of the IPT (Integrated Product Development Team) and engineering support technologies. Several prototype tools were developed, including product development process modeling and management, QFD-based schema design and decision making, PDM-based concurrent design, STEP-based CAD/CAPP/CAM integration, design for assembly, design for manufacturing, computer aided fixture design, and machining process simulation. Finally, the research results were used in the development of two complex components in an aerospace application, and satisfactory results were obtained.

  4. STU attractors from vanishing concurrence

    CERN Document Server

    Lévay, Péter

    2010-01-01

    Concurrence is an entanglement measure characterizing the {\\it mixed} state bipartite correlations inside of a pure state of an $n$-qubit system. We show that after organizing the charges and the moduli in the STU model of $N=2$, $d=4$ supergravity to a three-qubit state, for static extremal spherically symmetric BPS black hole solutions the vanishing condition for all of the bipartite concurrences on the horizon is equivalent to the attractor equations. As a result of this the macroscopic black hole entropy given by the three-tangle can be reinterpreted as a linear entropy characterizing the {\\it pure} state entanglement for an arbitrary bipartite split. Both for the BPS and non-BPS cases explicit expressions for the concurrences are obtained, with their vanishing on the horizon is demonstrated.

  5. Fuzzy simulation in concurrent engineering

    Science.gov (United States)

    Kraslawski, A.; Nystrom, L.

    1992-01-01

    Concurrent engineering is becoming a very important practice in manufacturing. A problem in concurrent engineering is the uncertainty associated with the values of the input variables and operating conditions. The problem discussed in this paper concerns the simulation of processes where the raw materials and the operational parameters possess fuzzy characteristics. The processing of fuzzy input information is performed by the vertex method and the commercial simulation packages POLYMATH and GEMS. The examples are presented to illustrate the usefulness of the method in the simulation of chemical engineering processes.

  6. Concurrency & Asynchrony in Declarative Workflows

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    Declarative or constraint-based business process and workflow notations have received increasing interest in the last decade as possible means of addressing the challenge of supporting at the same time flexibility in execution, adaptability and compliance. However, the definition of concurrent...... of concurrency in DCR Graphs admits asynchronous execution of declarative workflows both conceptually and by reporting on a prototype implementation of a distributed declarative workflow engine. Both the theoretical development and the implementation is supported by an extended example; moreover, the theoretical...

  7. Fuzzy simulation in concurrent engineering

    Science.gov (United States)

    Kraslawski, A.; Nystrom, L.

    1992-01-01

    Concurrent engineering is becoming a very important practice in manufacturing. A problem in concurrent engineering is the uncertainty associated with the values of the input variables and operating conditions. The problem discussed in this paper concerns the simulation of processes where the raw materials and the operational parameters possess fuzzy characteristics. The processing of fuzzy input information is performed by the vertex method and the commercial simulation packages POLYMATH and GEMS. The examples are presented to illustrate the usefulness of the method in the simulation of chemical engineering processes.

  8. Toxicity of concurrent radiochemotherapy for locally advanced non--small-cell lung cancer: a systematic review of the literature.

    Science.gov (United States)

    Koning, Caro C; Wouterse, Sanne J; Daams, Joost G; Uitterhoeve, Lon L; van den Heuvel, Michel M; Belderbos, José S

    2013-09-01

    Concurrent radiochemotherapy (RCT) is the treatment of choice for patients with locally advanced non-small-cell lung cancer (NSCLC). Two meta-analyses were inconclusive in an attempt to define the optimal concurrent RCT scheme. Besides efficacy, treatment toxicity will influence the appointed treatment of choice. A systematic review of the literature was performed to record the early and late toxicities, as well as overall survival, of concurrent RCT regimens in patients with NSCLC. The databases of PubMed, Ovid, Medline, and the Cochrane Library were searched for articles on concurrent RCT published between January 1992 and December 2009. Publications of phase II and phase III trials with ≥ 50 patients per treatment arm were selected. Patient characteristics, chemotherapy regimen (mono- or polychemotherapy, high or low dose) and radiotherapy scheme, acute and late toxicity, and overall survival data were compared. Seventeen articles were selected: 12 studies with cisplatin-containing regimens and 5 studies using carboplatin. A total of 13 series with mono- or polychemotherapy schedules--as single dose or double or triple high-dose or daily cisplatin-containing (≤ 30 mg/m(2)/wk) chemotherapy were found. Acute esophagitis ≥ grade 3 was observed in up to 18% of the patients. High-dose cisplatin regimens resulted in more frequent and severe hematologic toxicity, nausea, and vomiting than did other schemes. The toxicity profile was more favorable in low-dose chemotherapy schedules. From phase II and III trials published between 1992 and 2010, it can be concluded that concurrent RCT with monochemotherapy consisting of daily cisplatin results in favorable acute and late toxicity compared with concurrent RCT with single high-dose chemotherapy, doublets, or triplets.

  9. Two cycles of adjuvant carboplatin in stage I seminoma: 8-year experience by the Hellenic Cooperative Oncology Group (HECOG).

    Science.gov (United States)

    Koutsoukos, Konstantinos; Tzannis, Kimon; Christodoulou, Christos; Karavasilis, Vasilios; Bakoyiannis, Charalambos; Makatsoris, Thomas; Papandreou, C N; Pectasides, Dimitrios; Dimopoulos, Meletios A; Bamias, Aristotelis

    2016-06-01

    Following the establishment of adjuvant carboplatin in stage I testicular seminoma as a standard, we adopted this treatment for all stage I seminoma patients. We report our 8-year experience and compare these results with our previous adjuvant etoposide/cisplatin (EP) strategy. Patients with stage I seminoma, treated with adjuvant carboplatin and with a minimum follow-up of 1 year, were included. Two cycles of carboplatin [area under the curve (AUC) 6] were administered. A total of 138 patients with median age of 34 years, treated from September 2003 to December 2011, were selected. There were 5 relapses [5-year relapse-free rate (RFR) 96.8 % (95 % confidence interval 91.6-98.8)]: 3 relapses at retroperitoneal lymph nodes, 1 relapse at the adrenal gland, and 1 isolated brain metastasis. Four patients with relapse were cured with salvage chemotherapy. All patients with relapse had tumor diameter ≥4 cm and/or age ≤34 years. Patients with at least 1 of the above risk factors (n = 111) had a significantly higher relapse rate compared with a similar population (n = 64) treated with 2 cycles of adjuvant EP: 5-year RFR was 95 % (SE 2 %) versus 100 % (SE 0 %), (p = 0.067). Age and tumor diameter were associated with relapse in stage I seminoma treated with adjuvant carboplatin. Although adjuvant carboplatin in patients with age ≤34 and/or tumor diameter ≥4 cm is associated with higher relapse rates than EP, the prognosis of these patients is excellent, and therefore, the use of less toxic treatment is justified.

  10. Session-based concurrency, reactively

    NARCIS (Netherlands)

    M. Cano (Mauricio); J. Arias (Jaime); J.A. Pérez Parra (Jorge)

    2017-01-01

    textabstractThis paper concerns formal models for the analysis of communication-centric software systems that feature declarative and reactive behaviors. We focus on session-based concurrency, the interaction model induced by session types, which uses (variants of) the Π-calculus as specification

  11. Teaching Concurrency: Theory in Practice

    DEFF Research Database (Denmark)

    Aceto, Luca; Ingolfsdottir, Anna; Larsen, Kim Guldstrand

    2009-01-01

    in mathematics. We report here on our experiences in teaching concurrency theory over the last twenty years or so to students ranging from mathsphobic bachelor students to sophisticated doctoral students. The contents of the courses, the material on which they are based and the pedagogical philosophy underlying...

  12. Concurrency & Asynchrony in Declarative Workflows

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    Declarative or constraint-based business process and workflow notations have received increasing interest in the last decade as possible means of addressing the challenge of supporting at the same time flexibility in execution, adaptability and compliance. However, the definition of concurrent se...... development has been verified correct in the Isabelle-HOL interactive theorem prover....

  13. Relationships between models of concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Sassone, Vladimiro; Winskel, Glynn

    1994-01-01

    Models for concurrency can be classified with respect to the three relevant parameters: behaviour/system, interleaving/noninterleaving, linear/branching time. When modelling a process, a choice concerning such parameters corresponds to choosing the level of abstraction of the resulting semantics....... The classifications are formalized through the medium of category theory....

  14. Bisimulation for models in concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Clausen, Christian

    1994-01-01

    Recently, Joyal, Nielsen and Winskel suggested a categorical definition of bisimulation, applicable to a wide range of models in concurrency with an accompanying notion af observations. The definition is in terms of span of open maps, and it coincides with Park and Milner's strong bisimulation...

  15. The system of concurrent engineering

    NARCIS (Netherlands)

    Wognum, Nel; Trienekens, Jacques

    2015-01-01

    Concurrent engineering (CE) has been a major theme in the 80s and 90s of the previous century in research and practice. Its main aim is to reduce time-tomarket, improve quality and reduce costs by taking into account downstream requirements and constraints already in the design phase. While start

  16. Visualization of Concurrent Program Executions

    Science.gov (United States)

    Artho, Cyrille; Havelund, Klaus; Honiden, Shinichi

    2007-01-01

    Various program analysis techniques are efficient at discovering failures and properties. However, it is often difficult to evaluate results, such as program traces. This calls for abstraction and visualization tools. We propose an approach based on UML sequence diagrams, addressing shortcomings of such diagrams for concurrency. The resulting visualization is expressive and provides all the necessary information at a glance.

  17. Concurrency & Asynchrony in Declarative Workflows

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    Declarative or constraint-based business process and workflow notations have received increasing interest in the last decade as possible means of addressing the challenge of supporting at the same time flexibility in execution, adaptability and compliance. However, the definition of concurrent se...... development has been verified correct in the Isabelle-HOL interactive theorem prover....

  18. True Concurrency can be Traced

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik

    1990-01-01

    In this paper sets of labelled partial orders are employed as fundamental mathematical entities for modelling nondeterministic and concurrent processes thereby obtaining so-called noninterleaving semantics. Based on closures of sets of labelled partial orders, a simple algebraic language with ref...

  19. The composition of concurrent programs

    Science.gov (United States)

    Chandy, K. Mani; Taylor, Stephen

    1989-01-01

    A notation is presented for concurrent programs called program composition notation (PCN). The notation is being implemented at Caltech on multicomputers (a network of computers that communicate by sending and receiving messages). A fragment of this notation has been implemented on a data-parallel computer, the Connection Machine. The central ideas underlying PCN are discussed.

  20. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well as re...

  1. A Model for Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    1996-01-01

    We present a model for concurrent objects where obejcts interact by taking part in common events that are closely matched to form call-response pairs, resulting in resulting in rendez-vous like communications. Objects are built from primitive objects by parallel composition, encapsulation and hid...

  2. True Concurrency can be Traced

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik

    1990-01-01

    In this paper sets of labelled partial orders are employed as fundamental mathematical entities for modelling nondeterministic and concurrent processes thereby obtaining so-called noninterleaving semantics. Based on closures of sets of labelled partial orders, a simple algebraic language with ref...

  3. Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy.

    Science.gov (United States)

    Allen, Valerie A; Manahan, Kelly J; Geisler, John P

    2016-01-01

    Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient's diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

  4. Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

    Directory of Open Access Journals (Sweden)

    Valerie A. Allen

    2016-01-01

    Full Text Available Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI. Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient’s diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole. Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

  5. Acute pancreatitis induced by paclitaxel and carboplatin therapy in an ovarian cancer patient.

    Science.gov (United States)

    Shintani, D; Yoshida, H; Imai, Y; Fujiwara, K

    2016-01-01

    A 46-year-old female was treated with a regimen of paclitaxel and carboplatin (TC therapy) as adjuvant chemotherapy for Stage IC ovarian adenocarcinoma. There was no severe toxicity except for grade 3 neutropenia during the first four cycles of TC therapy. However, she developed acute pancreatitis at 14 days after fifth cycle. TC therapy is commonly associated with adverse effects such as myelosuppression, hypersensitivity, alopecia, and peripheral neuropathy, but acute pancreatitis has rarely been reported. Ovarian cancer patients often present with nausea and abdominal pain, which are the same symptoms of pancreatitis. It is very important to keep in mind that acute pancreatitis may be concealed in these common symptoms of ovarian cancer during and after TC therapy. Because acute pancreatitis is fatal complication and quitting the drug usually leads to complete cure. The authors report an uncommon case in which TC therapy may have caused acute pancreatitis.

  6. Isorhamnetin flavonoid synergistically enhances the anticancer activity and apoptosis induction by cis-platin and carboplatin in non-small cell lung carcinoma (NSCLC).

    Science.gov (United States)

    Zhang, Bao-Yi; Wang, Yan-Ming; Gong, Hai; Zhao, Hui; Lv, Xiao-Yan; Yuan, Guang-Hui; Han, Shao-Rong

    2015-01-01

    The development of novel antitumor drugs for the treatment of non-small cell lung carcinoma NSCLC is imperative in order to improve the efficacy of lung cancer therapy and prognosis. In the current study, we demonstrated the antitumor activity of isorhamnetin and its combinations with cisplatin and carboplatin against A-549 lung cancer cells. In order to assess the anticancer enhancing effect of isorhamnetin on cisplatin and carboplatin, A-549 cells were treated with isorhamnetin, cisplatin, carboplatin and their combinations and cell viability, cell apoptosis, cell cycle arrest as well as loss of mitochondrial membrane potential were evaluated by MTT assay, flow cytometry, confocal microscopy and fluorescence microscopy. The effect of the drugs on cancer cell migration, microtubule depolymerization as well activation of caspases was also studied. The results revealed that, as compared to single drug treatment, the combination of isorhamnetin with cisplatin and carboplatin resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Combination of isorhamnetin with cisplatin and carboplatin resulted in more potent apoptosis induction as revealed by fluorescence microscopy using AO/PI double staining. Isorhamnetin and its combinations also triggered microtubule distortion and depolymerization. The combination of isorhamnetin with cisplatin and carboplatin increased the number of cells in G2/M phase dramatically as compared to single drug treatment. Moreover, isorhamnetin and its combinations with known anticancer drugs induced disruption of the mitochondrial membrane potential as well as activation of caspases 3, 9 and poly-(ADP-ribose) polymerase in A-549 cells. Isorhamnetin as well as its combinations with cisplatin and carboplatin resulted in inhibition of cancer cell migration significantly. Results of the current study suggest that isorhamnetin combinations with cisplatin and carboplatin might be a potential clinical chemotherapeutic

  7. Enhanced Antiproliferative Effect of Carboplatin in Cervical Cancer Cells Utilizing Folate-Grafted Polymeric Nanoparticles

    Science.gov (United States)

    Ji, Jing; Zuo, Ping; Wang, Yue-Ling

    2015-11-01

    Carboplatin (CRB) possesses superior anticancer effect in cervical cancer cells with lower incidence of side effects compared to that of cisplatin. However, CRB suffers from severe side effects due to undesirable tissue distributions which contribute to the low therapeutic efficacy. Here, we report a unique folic acid-conjugated chitosan-coated poly( d- l-lactideco-glycolide) (PLGA) nanoparticles (FPCC) prepared for the selective delivery of carboplatin to the cervical cancer cells. The particles were nanosized and spherical shaped with size less than HeLa cells than compared to non-targeted nanoparticles. Selective uptake of FPCC was due to an interaction of folic acid (FA) with the folate receptors alpha (FRs-α) which is overexpressed on the HeLa and promoted active targeting. These results indicated that FPCC had a specific affinity for the cancerous, HeLa cells owing to ligand-receptor (FA-FR-α) recognition. Consistently, FPCC showed superior cytotoxic effect than any other formulations. The IC50 (concentration of the drug required to kill 50 % of the cells) value of FPCC was 0.65 μg/ml while it was 1.08, 1.56, and 2.35 μg/ml for PCC, PLGA NP, and free CRB, respectively. Consistent with the cytotoxicity assay, FPCC induced higher fraction of early as well as late apoptosis cells. Especially, FPCC induced nearly 45 % of early apoptosis cells and more than 35 % in late apoptosis. Therefore, we propose that folate-conjugated nanoparticles might have potential applications in cervical cancer therapy.

  8. Copper Transporter 2 Regulates the Cellular Accumulation and Cytotoxicity of Cisplatin and Carboplatin

    Science.gov (United States)

    Blair, Brian G.; Larson, Christopher A.; Safaei, Roohangiz; Howell, Stephen B.

    2010-01-01

    Purpose Copper transporter 2 (CTR2) is known to mediate the uptake of Cu+1 by mammalian cells. Several other Cu transporters, including the influx transporter CTR1 and the two efflux transporters ATP7A and ATP7B, also regulate sensitivity to the platinum-containing drugs. We sought to determine the effect of CTR2 on influx, intracellular trafficking, and efflux of cisplatin and carboplatin. Experimental Design The role of CTR2 was examined by knocking down CTR2 expression in an isogenic pair of mouse embryo fibroblasts consisting of a CTR1+/+ line and a CTR1−/− line in which both CTR1 alleles had been deleted. CTR2 levels were determined by quantitative reverse transcription-PCR and Western blot analysis. Cisplatin (DDP) was quantified by inductively coupled plasma mass spectrometry and 64Cu and [14C]carboplatin (CBDCA) accumulation by γ and scintillation counting. Results Deletion of CTR1 reduced the uptake of Cu, DDP, and CBDCA and increased resistance to their cytotoxic effects by 2- to 3-fold. Knockdown of CTR2 increased uptake of Cu only in the CTR1+/+ cells. In contrast, knockdown of CTR2 increased whole-cell DDP uptake and DNA platination in both CTR1+/+ and CTR1−/− cells and proportionately enhanced cytotoxicity while producing no effect on vesicular accumulation or efflux. A significant correlation was found between CTR2 mRNA and protein levels and sensitivity to DDP in a panel of six ovarian carcinoma cell lines. Conclusions CTR2 is a major determinant of sensitivity to the cytotoxic effects of DDP and CBDCA. CTR2 functions by limiting drug accumulation, and its expression correlates with the sensitivity of human ovarian carcinoma cell lines to DDP. PMID:19509135

  9. Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells.

    Science.gov (United States)

    Busschots, Steven; O'Toole, Sharon; O'Leary, John J; Stordal, Britta

    2015-08-01

    A major risk factor for ovarian cancer is germline mutations of BRCA1/2. It has been found that (80%) of cellular models with acquired platinum or taxane resistance display an inverse resistance relationship, that is collateral sensitivity to the other agent. We used a clinically relevant comparative selection strategy to develop novel chemoresistant cell lines which aim to investigate the mechanisms of resistance that arise from different exposures of carboplatin and taxol on cells having BRCA1 function (UPN251) or dysfunction (OVCAR8). Resistance to carboplatin and taxol developed quicker and more stably in UPN251 (BRCA1-wildtype) compared to OVCAR8 (BRCA1-methylated). Alternating carboplatin and taxol treatment delayed but did not prevent resistance development when compared to single-agent administration. Interestingly, the sequence of drug exposure influenced the resistance mechanism produced. UPN251-6CALT (carboplatin first) and UPN251-6TALT (taxol first) have different profiles of cross resistance. UPN251-6CALT displays significant resistance to CuSO4 (2.3-fold, p=0.004) while UPN251-6TALT shows significant sensitivity to oxaliplatin (0.6-fold, p=0.01). P-glycoprotein is the main mechanism of taxol resistance found in the UPN251 taxane-resistant sublines. UPN251 cells increase cellular glutathione levels (3.0-fold, p=0.02) in response to carboplatin treatment. However, increased glutathione is not maintained in the carboplatin-resistant sublines. UPN251-7C and UPN251-6CALT are low-level resistant to CuSO4 suggesting alterations in copper metabolism. However, none of the UPN251 sublines have alterations in the protein expression of ATP7A or CTR1. The protein expression of BRCA1 and MRP2 is unchanged in the UPN251 sublines. The UPN251 sublines remain sensitive to parp inhibitors veliparib and CEP8983 suggesting that these agents are candidates for the treatment of platinum/taxane resistant ovarian cancer patients.

  10. Structural studies of the effect that dimethyl sulfoxide (DMSO) has on cisplatin and carboplatin binding to histidine in a protein.

    Science.gov (United States)

    Tanley, Simon W M; Schreurs, Antoine M M; Kroon-Batenburg, Loes M J; Meredith, Joanne; Prendergast, Richard; Walsh, Danielle; Bryant, Patrick; Levy, Colin; Helliwell, John R

    2012-05-01

    The anticancer complexes cisplatin and carboplatin target the DNA major groove, forming intrastrand and interstrand cross-links between guanine bases through their N7 atoms, causing distortion of the DNA helix and apoptotic cell death. A major side effect of these drugs is toxicity, which is caused via binding to many proteins in the body. A range of crystallographic studies have been carried out involving the cocrystallization of hen egg-white lysozyme (HEWL) as a test protein with cisplatin and carboplatin in aqueous and dimethyl sulfoxide (DMSO) conditions. Different cryoprotectants, glycerol and Paratone, were used for each of the cisplatin and carboplatin cocrystallization cases, while silicone oil was used for studies involving N-acetylglucosamine (NAG). Both cisplatin and carboplatin do not bind to HEWL in aqueous media on the timescales of the conditions used here, but upon addition of DMSO two molecules of cisplatin or carboplatin bind either side of His15, which is the only His residue in lysozyme and is assumed to be an imidazolyl anion or a chemical resonance moiety, i.e. both imidazole N atoms are chemically reactive. To identify the platinum-peak positions in the 'with DMSO conditions', anomalous scattering maps were calculated as a cross-check with the F(o) - F(c) OMIT maps. Platinum-occupancy σ values were established using three different software programs in each case. The use of EVAL15 to process all of the diffraction data sets provided a consistent platform for a large ensemble of data sets for the various protein and platinum-compound model refinements with REFMAC5 and then SHELXTL. Overall, this extensive set of crystallization and cryoprotectant conditions allowed a systematic evaluation of cisplatin and carboplatin binding to lysozyme as a test protein via detailed X-ray crystal structure characterizations. DMSO is used as a super-solvent for drug delivery as it is deemed to cause no effect upon drug binding. However, these results show

  11. Data refinement for true concurrency

    Directory of Open Access Journals (Sweden)

    Brijesh Dongol

    2013-05-01

    Full Text Available The majority of modern systems exhibit sophisticated concurrent behaviour, where several system components modify and observe the system state with fine-grained atomicity. Many systems (e.g., multi-core processors, real-time controllers also exhibit truly concurrent behaviour, where multiple events can occur simultaneously. This paper presents data refinement defined in terms of an interval-based framework, which includes high-level operators that capture non-deterministic expression evaluation. By modifying the type of an interval, our theory may be specialised to cover data refinement of both discrete and continuous systems. We present an interval-based encoding of forward simulation, then prove that our forward simulation rule is sound with respect to our data refinement definition. A number of rules for decomposing forward simulation proofs over both sequential and parallel composition are developed.

  12. PyCSP - controlled concurrency

    DEFF Research Database (Denmark)

    Vinter, Brian; Friborg, Rune Møllegaard; Bjørndalen, John Markus

    2010-01-01

    Producing readable and correct programs while at the same time taking advantage of multi-core architectures is a challenge. PyCSP is an implementation of Communicating Sequential Processes algebra (CSP) for the Python programming language, that take advantage of CSP's formal and verifiable approach...... to controlling concurrency and the readability of Python source code. We describe PyCSP, demonstrate it through examples and demonstrate how PyCSP compares to Pthreads in a master-worker benchmark....

  13. PyCSP - controlled concurrency

    DEFF Research Database (Denmark)

    Friborg, Rune Møllegaard; Vinter, Brian; Bjørndalen, John Markus

    Producing readable and correct programs while at the same time taking advantage of multi-core architectures is a challenge. PyCSP is an implementation of Communicating Sequential Processes algebra (CSP) for the Python programming language, taking advantage of CSP’s formal and verifiable approach...... to controlling concurrency and the readability of Python source code. We describe PyCSP, demonstrate it through examples and demonstrate how PyCSP compares to Pthreads using a benchmark....

  14. The Therapeutic Efficacy of Continous Regional Intra-arterial Infusion(CRI) of Sandostatin and Antibiotics in Patients of Severe Acute Pancreatitis%区域灌注及早期中药治疗重症急性胰腺炎

    Institute of Scientific and Technical Information of China (English)

    李建国

    2014-01-01

    Objective:To evaluate the therapeutic efficacy of continous regional intra -arterial infusion(CRI) of sandostatin and Antibi-otics in patients of severe acute pancreatitis (SAP).Methods:Twenty nine cases of SAP patients were randomly divided in -to two groups. Group of CRI,13 cases and control group,16 cases.Seldingers method was used in brief, placing a catheter in the pancreatic regional artery such as gastropyloric artery , irrigating the inflamed area of the pancreas , and infusing sandostatin and antibiotics to control inflammation and prevent secondary infection by continuous pumping for 24h.Results:Abdominal sings and pain were apparently relieved after 24h of treat-ment, disappeared in 7-12days.Twelve cases were cured .Clinical Manifestations in control group lasted much longer compared with CRI group, after 5-7days of the treatment , abdominal signs Began subsiding .Conclusion:Continous regional intra -arterial infusion for the treatment of severe acute pancreatitis can prevent The development of pancreatic infection and big cut the course of treatment .%目的:评价经胰血管留置导管持续区域灌注生长抑素和抗生素治疗重症急性胰腺炎( SAP)的疗效。方法:将29例SAP患者分为区域灌注及早期中药治疗组(13例)和常规给药组(16例)。区域灌注及早期中药治疗组经股动脉超选择插管至胰腺坏死的供血动脉留置导管,用微泵持续24小时灌注生长抑素及抗生素,症状体征消失后拔管。常规给药组用静脉输注药物,药物用量及剂量完全同区域灌注组。结果:灌注组治疗后48小时腹部体征明显改善,腹痛减轻,7~12天症状全部消失,病情无复发,疗程平均20天,均痊愈出院。常规给药组治疗后5~7天见腹部体征改善,病情有反复,疗程45天~4个月,平均57天。常规给药组出现严重并发症13例次,死亡4例。结论:经胰血管置管持续区域灌注生长抑素及

  15. Debugging Concurrent Software:Advances and Challenges

    Institute of Scientific and Technical Information of China (English)

    Jeff Huang; Charles Zhang

    2016-01-01

    Concurrency debugging is an extremely important yet challenging problem that has been hampering developer productivity and software reliability in the multicore era. We have worked on this problem in the past eight years and have developed several effective methods and automated tools for helping developers debugging shared memory concurrent programs. This article discusses challenges in concurrency debugging and summarizes our research contributions in four important directions: concurrency bug reproduction, detection, understanding, and fixing. It also discusses other recent advances in tackling these challenges.

  16. Effects observation of subcutaneous intra-arterial chemotherapy with subcutaneously implanted pump for extremity soft tissues sarcoma and cancerous ulcer%术前皮下埋植式化疗泵动脉介入化疗四肢软组织肉瘤与癌性溃疡的疗效观察

    Institute of Scientific and Technical Information of China (English)

    刘铖; 李鼎锋; 崔秋; 郭钧

    2015-01-01

    Objective To observe the efficiency of subcutaneous intra-arterial chemotherapy with subcutaneously implanted pump for extremity soft tissues sarcoma and cancerous ulcer.Methods Thirty-one patients with ulcerative skin squamous cell carcinoma or soft tissues sarcoma of extremities received treatment from July 2003 to November 2011,including 15 males and 16 females.The average age was 49 years old ( range: 14-83 years ).Ten patients had sarcoma in upper extremities and 21 patients in lower extremities.The pathological types of studied cases included 9 cases with skin squamous cell carcinoma,6 cases with synovial sarcoma,5 cases with malignant fibrous histiocytoma,3 cases with liposarcoma,3 cases with osteosarcoma,2 cases with malignant melanoma,2 cases with epidermoid sarcoma,and 1 case with protuberans.The main symptoms of cancerous ulcer were pain,infection and hemorrhage.All the studied patients were administrated with cisplatin ( 120 mg / m2 ) and doxorubicin ( 90 mg / m2 ) by intra-arterial chemotherapy pump,and the patients with squamous cell carcinoma were additionally applied with bleomycin ( 15 mg ) and patients with malignant melanoma were applied with dacarbazine ( 600 mg / m2 ).The chemotherapy efifciency was observed after at 2-3 cycles of intra-arterial chemotherapy.Surgical or conservative treatment was chosen according to tumor boundary and blood supply after chemotherapy.Pain and pain relief were observed in patients pre-treatment and post-treatment.Effects on solid tumors were evaluated according to WHO ( World Hearth Organization ) criteria.Results The mean follow-up was 67 months in this group.( 1 ) Before the treatment,moderate pain was in 18 cases,severe pain in 13 cases.Pain relief was achieved after one cycle of chemotherapy,including complete remission ( CR ) 19 cases,partial remission ( PR ) 8 cases,mild remission ( MR ) 4 cases.The total remission rate of pain ( RR ) was 87%.There were only four cases of mild pain after three times of

  17. Concurrent chemoradiation for vaginal cancer.

    Directory of Open Access Journals (Sweden)

    David T Miyamoto

    Full Text Available BACKGROUND: It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer treated with radiation therapy (RT or concurrent chemoradiation therapy (CRT. METHODS: Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS and disease-free survival (DFS rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed. RESULTS: The median age at diagnosis was 61 years (range, 18-92 years and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p = 0.037; 3-yr DFS = 43% vs. 73%, log-rank p = 0.011. Twenty-three patients (45% in the RT group had a relapse at any site compared to 3 (15% in the CRT group (p = 0.027. With regard to the sites of first relapse, 10 patients (14% had local only, 4 (6% had local and regional, 9 (13% had regional only, 1 (1% had regional and distant, and 2 (3% had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10-0.97; p = 0.04. CONCLUSIONS: Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients.

  18. Simple concurrent garbage collection almost without synchronization

    NARCIS (Netherlands)

    Hesselink, Wim H.; Lali, M.I.

    2010-01-01

    We present two simple mark and sweep algorithms, A and B, for concurrent garbage collection by a single collector running concurrently with a number of mutators that concurrently modify shared data. Both algorithms are based on the ideas of Ben-Ari's classical algorithm for on-the-fly garbage collec

  19. Simple concurrent garbage collection almost without synchronization

    NARCIS (Netherlands)

    Hesselink, Wim H.; Lali, M.I.

    We present two simple mark and sweep algorithms, A and B, for concurrent garbage collection by a single collector running concurrently with a number of mutators that concurrently modify shared data. Both algorithms are based on the ideas of Ben-Ari's classical algorithm for on-the-fly garbage

  20. Effects of intra-arterial infusion of 3-bromopyruvate on metastases and survival benefit of hepatic VX2 tumor in rabbits%3-溴丙酮酸对兔VX2肝肿瘤转移及兔生存时间的影响

    Institute of Scientific and Technical Information of China (English)

    江雄鹰; 张小萍; 黄金华; 罗荣光; 苗碧建; 王琰

    2013-01-01

    目的 探讨3-溴丙酮酸(3-BrPA)经肝动脉灌注对兔VX2肝肿瘤转移及荷瘤兔生存时间的影响.方法 18只新西兰大白兔肝左叶种植VX2肿瘤,随机分成3组,每组6只.PBS灌注组:在肿瘤种植14 d后行肝动脉PBS溶液灌注.3-BrPA 7和14 d灌注组:在肿瘤种植7/14 d后行肝动脉3-BrPA溶液灌注.在肿瘤种植28 d后每组处死3只兔,解剖探查有无肝内转移、肾转移、肺转移及腹腔转移.每组剩余的3只兔观察其生存时间并进行比较.结果 肿瘤种植28 d后,PBS灌注组均发现肝内及腹腔转移(3/3),肾转移2只(2/3),肺转移2只(2/3).3-BrPA 7 d灌注组实验兔肝内和肺转移各有1只(1/3),未发现有腹腔和肾转移(0/3).3-BrPA14 d灌注组实验兔有2只发现肝内转移(2/3),肺和腹腔转移各有1只(1/3),未发现肾转移(0/3).生存时间比较显示3-BrPA 14 d灌注组实验兔生存时间[(27±5)d]显著长于PBS溶液灌注组[(17±3)d](P=0.041).而3-BrPA 7 d灌注组实验兔生存时间[(42±6)d]显著长于3-BrPA 14 d灌注组实验兔[(27±5)d](P=0.007).结论 经肝动脉灌3-BrPA能够有效减少兔VX2肝肿瘤的转移,并可延长移植VX2肝肿瘤兔的生存时间,且灌注时间越早,治疗效果越好.%Objective To evaluate the metastasis and survival of an intra-arterial infusion of 3-bromopyruvate (3-BrPA) on hepatic VX2 tumor in rabbits.Methods VX2 tumor was implanted in left lateral lobe of liver of 18 white New Zealand rabbits.The animals were randomized into 3 groups (n =6 each) and underwent an intra-arterial infusion of phosphate-buffered saline or 3-BrPA via hepatic artery at 14 days post-implantation.At 28 days post-implantation,3 rabbits in each group were sacrificed.The abdomen of these rabbits was opened and inspected for metastases.Then the survival of the remaining rabbits was observed.Results At 28 days post-implantation,in PBS group,there were intrahepatic metastasis and abdominal cavity dissemination (n =3),renal metastases (n =2

  1. 局部晚期膀胱癌术前动脉灌注新辅助化疗的安全性与疗效分析%Safety and efficacy of intra-arterial infusion neoadjuvant chemotherapy for local advanced bladder cancer

    Institute of Scientific and Technical Information of China (English)

    牛亦农; 闫勇; 张军晖; 康宁; 王建文; 田溪泉; 王学科; 邢念增

    2009-01-01

    Objective To evaluate the safety and efficacy of intra-arterial infusion neoadiuvant chemotherapy in local advanced bladder cancer. Methods Nineteen cases with T2-T4a bladder cancer were enrolled in this study.Intra-arterial infusion chemotherapy with Gemcitabine and Cisplatin (GC)were performed for 1 to 3 cycles before radical cystectomy.Postoperative values of hematological parameters,maximum diameter of tumors,TNM(tumor,node and metastasis)stages and pathological grades were compared with preoperative parameters of the same case. Results Compared to the values before GC chemotherapy,WBC count showed no significant change post-operative,(6.63±2.58)×109/L vs(5.12±2.91)×109/L(P=0.13);RBC(4.41+0.52)×1012/L vs(3.92±0.42)×1012/L(P=0.00)and platelet count(220.50±59.86)×109/L vs(157.05±56.72)×109/L(P=0.001)showed significant decrease;ALT did not show significant decrease(20.00±8.31 vs 26.88±17.04 U/L,P=0.08);Creatltme also showed no significant change(95.82±14.57 vs 88.04±17.76μmol/L,P=0.06);Maximum diameter of tumors decreased significantly(3.72±1.23 vs 2.80±1.29 cm,P=0.02).Compared with clinical TNM stages,pathological TNM stages demonstrated significant decrease in 9 cases;While cell differentiation did not show decrease. Conclusions Intra-arterial infusion with GC regimen can reduce tumor size,decrease TNM stages,while not causing significant adverse impact to radical cystectomy.Bladder-spare treatment is an option for chemotherapy-sensitive cases.%目的 探讨根治性膀胱切除术前动脉灌注化疗治疗局部晚期膀胱癌的安全性与疗效.方法 局部晚期膀胱癌患者(T2~T4a)19例,采用2-脱氧-2,2-盐酸二氟脱氧胞苷(β-异构体)与(顺)二氨二氯铂(GC)方案髂内动脉灌注化疗1~3次,随后行膀胱根治性切除术或经尿道膀胱肿瘤电切术,2例肿瘤缩小者拒绝手术治疗,2例经术前评价不能承受手术治疗.统计学分析比较化疗前后患者血白细胞、红细胞、血小板水

  2. Toxicity and prognosis in overweight and obese women with lung cancer receiving carboplatin-paclitaxel doublet chemotherapy.

    Science.gov (United States)

    Kashiwabara, Kosuke; Yamane, Hiromi; Tanaka, Hideyuki

    2013-05-01

    We retrospectively analyzed overdosing-related toxicity and prognosis in 127 women with lung cancer receiving carboplatin (6AUC) estimated by the Cockcroft-Gault formula using actual body weight and paclitaxel (200 mg/m(2)). Between the body mass index (BMI) > 25 group (n = 42) and the BMI ≤ 25 group (n = 85), there was no difference in dose intensity of carboplatin (122 mg/m(2)/week vs. 124 mg/m(2)/week, p = .323), median overall survival (285 days vs. 282 days, p = .820), and toxicity, except Grade 4 neutropenia in the second cycle. Women with BMI > 25 did not have an increased risk of toxicity because of an appropriate dose reduction.

  3. [Carboplatin plus irinotecan induced partial response in a patient with small cell carcinoma of the prostate; a case report].

    Science.gov (United States)

    Kimura, Hiroko; Uegaki, Masayuki; Aoyama, Teruyoshi; Kawai, Jun; Hamano, Toshiaki; Hashimura, Takayuki

    2014-01-01

    An 80-year-old man with prostate cancer receiving hormone therapy presented with urinary retention. The computed tomographic scan showed metastases to the lung, liver, and lymph nodes, as well as increased prostate volume. Transurethral resection of the prostate (TURP) was performed, and the resected specimen was pathologically found to be a small cell carcinoma of the prostate. The patient was treated with a combination of carboplatin and irinotecan, and achieved a partial response : size reduction of the prostate and the metastatic lesions, and decreased neuron specific enolase (NSE) level. The chemotherapy with carboplatin and irinotecan is reported to have fewer serious adverse effects, and equivalent efficacy to the cisplatin/etoposide chemotherapy. Therefore, this regimen could also be a treatment option for the patients with small cell carcinoma of the prostate.

  4. Randomized cross-over clinical trial to study potential pharmacokinetic interactions between cisplatin or carboplatin and etoposide

    Science.gov (United States)

    Thomas, Huw D; Porter, David J; Bartelink, Imke; Nobbs, Joy R; Cole, Michael; Elliott, Suzie; Newell, David R; Calvert, A Hilary; Highley, Martin; Boddy, Alan V

    2002-01-01

    Aims Cisplatin and carboplatin are often used in combination with etoposide. In a randomized cross-over study, the potential interaction between the two platinum drugs and the metabolism of etoposide was explored. In vitro investigations using human liver microsomes were also performed. Methods Etoposide was administered to 15 patients over 3 days, with the platinum drug administered on day 2. The alternate platinum drug was administered on the second course. The pharmacokinetics of etoposide were determined on all 3 days of each cycle. The effect of platinum drugs on etoposide metabolism by human liver enzymes was explored in vitro. Results Neither cisplatin nor carboplatin coadministration affected the pharmacokinetics of etoposide during cycle 1. When carboplatin was administered on course 2, etoposide AUC was 8% higher on day 2 compared with day 1 or day 3 (for day 2 vs day 3, 95% CI: −0.72, −0.08 mg ml−1 min). In contrast, cisplatin on course 2 increased the AUC of etoposide (28%) on day 3 (day 3 vs day 1, 95% CI: 0.67, 2.09 mg ml−1 min), with no effect on day 2. In vitro carboplatin and cisplatin (10–100 µm) inhibited the metabolism of etoposide, if rat liver microsomes were preincubated (30 min) with NADPH and the platinum complexes. With human liver microsomes a small effect on etoposide metabolism, but not on catechol formation, was observed. Conclusions The interaction between etoposide and platinum drugs is small and, given the pharmacokinetic variability seen with etoposide, the clinical impact is unlikely to be significant. PMID:11849199

  5. The impact of paclitaxel and carboplatin chemotherapy on the autonomous nervous system of patients with ovarian cancer

    OpenAIRE

    2016-01-01

    Background Paclitaxel-based regimens are frequently associated with the development of peripheral neuropathy. The autonomous nervous system (ANS) effects, however, of this chemotherapeutic agent remain unexplored. Methods We investigated a group of 31 female patients with ovarian cancer receiving treatment with paclitaxel and carboplatin, as well as a group of 16 healthy age- and gender-matched healthy volunteers. All study participants completed a questionnaire and were assessed neurophysiol...

  6. Squalene Selectively Protects Mouse Bone Marrow Progenitors Against Cisplatin and Carboplatin-Induced Cytotoxicity In Vivo Without Protecting Tumor Growth

    Directory of Open Access Journals (Sweden)

    Bikul Das

    2008-10-01

    Full Text Available Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against chemotherapy-induced toxicity. We have previously published that squalene protects light-density bone marrow cells against cis-diamminedichloroplatinum( II (cisplatin-induced toxicity without protecting tumor cells in vitro. Here, we developed an in vivo mouse model of cisplatin and cis-diammine (cyclobutane-1,1-dicarboxylato platinum(II (carboplatin-induced toxicity to further investigate squalene-mediated LD-BM cytoprotection including the molecular mechanism behind selective cytoprotection. We found that squalene significantly reduced the body weight loss of cisplatin and carboplatin-treated mice. Light-density bone marrow cells from squalene-treated mice exhibited improved formation of hematopoietic colonies (colony-forming unit-granulocyte macrophage. Furthermore, squalene also protected mesenchymal stem cell colonies (colony-forming unit-fibroblast from cisplatin and carboplatin-induced toxicity. Squalene-induced protection was associated with decreased reactive oxygen species and increased levels of glutathione and glutathione peroxidase/glutathione-S-transferase. Importantly, squalene did not protect neuroblastoma, small cell carcinoma, or medulloblastoma xenografts against cisplatin-induced toxicity. These results suggest that squalene is a potential candidate for future development as a cytoprotective agent against chemotherapeutic toxicity.

  7. A phase 1b dose expansion study of the pan-class I PI3K inhibitor buparlisib (BKM120) plus carboplatin and paclitaxel in PTEN deficient tumors and with dose intensified carboplatin and paclitaxel.

    Science.gov (United States)

    Smyth, Lillian M; Monson, Kelsey R; Jhaveri, Komal; Drilon, Alexander; Li, Bob T; Abida, Wassim; Iyer, Gopa; Gerecitano, John F; Gounder, Mrinal; Harding, James J; Voss, Martin H; Makker, Vicky; Ho, Alan L; Razavi, Pedram; Iasonos, Alexia; Bialer, Philip; Lacouture, Mario E; Teitcher, Jerrold B; Erinjeri, Joseph P; Katabi, Nora; Fury, Matthew G; Hyman, David M

    2017-03-09

    Purpose We previously reported the phase I dose escalation study of buparlisib, a pan-class 1A PI3K inhibitor, combined with platinum/taxane-based chemotherapy in patients with advanced solid tumors. The combination was well tolerated and promising preliminary efficacy was observed in PTEN deficient tumors. This phase I dose expansion study now evaluates buparlisib plus high dose carboplatin and paclitaxel in unselected patients with advanced solid tumors and buparlisib plus standard dose carboplatin and paclitaxel in patients with PTEN deficient tumors (ClinicalTrials.gov, NCT01297452). Methods There were two expansion cohorts: Cohort A received continuous buparlisib (100 mg/daily) orally plus high dose carboplatin AUC 6 and paclitaxel 200 mg/m2; Cohort B treated patients with PTEN deficient tumors only and they received the recommended phase II dose (RP2D) of continuous buparlisib (100 mg/daily) orally plus standard dose carboplatin AUC 5 and paclitaxel 175 mg/m2. Both cohorts received chemotherapy intravenously on day 1 of the 21-day cycle with pegfilgrastim support. Primary endpoint in Cohort A was to evaluate the safety and tolerability of chemotherapy dose intensification with buparlisib and in Cohort B was to describe preliminary efficacy of the combination among patients with tumors harboring a PTEN mutation or homozygous deletion. Results 14 subjects were enrolled, 7 in Cohort A and 7 in Cohort B. Dose reductions were required in 5 (71%) and 3 (43%) patients, in cohort A and B respectively. Grade 3 adverse events in Cohort A included lymphopenia (n = 5 [71%]), hyperglycemia (n = 2, [29%]), diarrhea (n = 2, [29%]) and rash (n = 2, [29%]) and in cohort B included lymphopenia (n = 5 [71%]), hyperglycemia (n = 4 [57%]) and neutropenia (n = 2 [29%]. The mean number of cycles on protocol was 6. The overall objective response rate was 14% (2 /14). No objective responses were observed in the PTEN deficient cohort. Four out of 6 patients with

  8. Concurrent fractional and equilibrium crystallisation

    Science.gov (United States)

    Sha, Lian-Kun

    2012-06-01

    This paper proposes the concept of concurrent fractional and equilibrium crystallisation (CFEC) in a multi-phase magmatic system in light of experimental results on diffusivities of elements and other species in minerals and melts. A group of equations are presented to describe how the concentrations of an element or isotope change in fractionated solid, equilibrated solid, melt, liquid, and gas phases, as well as in magma, as a function of distribution coefficients and mass fractions during the CFEC process. CFEC model is a generalised and unified formulation that is valid, not only for pure fractional crystallisation (FC) and perfect equilibrium crystallisation (EC) singly, as two of its limiting end-member cases, but also for the geologically more important process of concurrent fractional and equilibrium crystallisation. The concept that both fractional and equilibrium crystallisation can operate concurrently in a magmatic system, for a given element, among different minerals, and even within different-sized crystal grains of the very same mineral phase, is of fundamental importance in deepening our current understanding of magmatic differentiation processes. CFEC probably occurs more frequently in the natural world than either pure fractional or perfect equilibrium crystallisation alone, as a result of the interplay of varying diffusivities of elements under diverse physicochemical conditions, different residence time and growth rates of mineral phases in magmas, and varying grain sizes within each phase and among different phases. The marked systematic variations in trace element concentrations in the melts of the Bishop Tuff have long been perplexing and difficult to reconcile with existing models of differentiation. CFEC, which is able to better explain the scatter trends in a systematic way than fractional crystallisation, is considered to be the cause.

  9. Concurrent engineering teams. Volume 2: Annotated bibliography

    Science.gov (United States)

    Richter, Karen J.; Dierolf, David A.

    1990-11-01

    Specific concurrent engineering practices vary among organizations. There are, however, various management practices that appear to work well for most organizations. This paper presents the reader with specific, useful examples from several defense contractors illustrating how multifunctional concurrent engineering teams are being organized and managed and how concurrent engineering team meetings are conducted and supported. The types of computer support that could be used to enhance the efficiency and effectiveness of concurrent engineering team meetings are identified. The general findings are that there exists a direct relationship between total quality management (TQM) and concurrent engineering, and that many applications of computer-aided group problem solving are possible and practical today for the concurrent engineering team meetings. Areas identified for additional research are the documentation of the decision process and rationale during the product and process definition, the capturing of lessons learned during the implementation of concurrent engineering, and the performance evaluation and training of team members.

  10. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    period of delay can potentially be attributed to several events falling within both parties' spheres of responsibility, commonly termed concurrent delay, is rarely regulated in construction contracts in spite of its common occurrence. This book analyses both the theoretical foundations and the practical......Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing...

  11. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing...... period of delay can potentially be attributed to several events falling within both parties' spheres of responsibility, commonly termed concurrent delay, is rarely regulated in construction contracts in spite of its common occurrence. This book analyses both the theoretical foundations and the practical...

  12. Barriers in Concurrent Separation Logic

    Science.gov (United States)

    Hobor, Aquinas; Gherghina, Cristian

    We develop and prove sound a concurrent separation logic for Pthreads-style barriers. Although Pthreads barriers are widely used in systems, and separation logic is widely used for verification, there has not been any effort to combine the two. Unlike locks and critical sections, Pthreads barriers enable simultaneous resource redistribution between multiple threads and are inherently stateful, leading to significant complications in the design of the logic and its soundness proof. We show how our logic can be applied to a specific example program in a modular way. Our proofs are machine-checked in Coq.

  13. Preparing HEP software for concurrency

    Science.gov (United States)

    Clemencic, M.; Hegner, B.; Mato, P.; Piparo, D.

    2014-06-01

    The necessity for thread-safe experiment software has recently become very evident, largely driven by the evolution of CPU architectures towards exploiting increasing levels of parallelism. For high-energy physics this represents a real paradigm shift, as concurrent programming was previously only limited to special, well-defined domains like control software or software framework internals. This paradigm shift, however, falls into the middle of the successful LHC programme and many million lines of code have already been written without the need for parallel execution in mind. In this paper we have a closer look at the offline processing applications of the LHC experiments and their readiness for the many-core era. We review how previous design choices impact the move to concurrent programming. We present our findings on transforming parts of the LHC experiment reconstruction software to thread-safe code, and the main design patterns that have emerged during the process. A plethora of parallel-programming patterns are well known outside the HEP community, but only a few have turned out to be straightforward enough to be suited for non-expert physics programmers. Finally, we propose a potential strategy for the migration of existing HEP experiment software to the many-core era.

  14. Combined radiotherapy with cis- or carboplatin in advanced head and neck tumours. Kombinierte Radiotherapie mit Cis- oder Carboplatin bei fortgeschrittenen Kopf-Hals-Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Zamboglou, N.; Pape, H.; Schnabel, T.; Wurm, R.; Bannach, B.; Fuerst, G.; Schmitt, G. (Duesseldorf Univ. (Germany, F.R.). Klinik fuer Strahlentherapie und Radiologische Onkologie)

    1989-09-01

    This report reviews the treatment results of 111 patients with stage T3-4, N0-3, M0, biopsy proven squamous cell carcinoma of the oropharynx and oral cavity. All patients were treated by primary irradiation with 1.8 to 2 Gy per day for five days a week up to a target volume dose of 39,6 or 40 Gy. Simultaneously 20 mg/m{sup 2} cisplatin was given under hyperhydration and mannitol diuresis on days 1 to 5. In case of partial tumour regression radiotherapy was continued up to 70 Gy with another course of cisplatin. In case of minor response surgery was interposed followed by subsequent irradiation with 30 Gy and a second course of cisplatin. 67% of the patients showed an initial complete tumour involution and 27% a partial response. The five year actuarial survival rate with a minimum follow-up of two years is 47,6%. More than 96% of the long term survivors showed a complete response after the end of treatment. Carboplatin (CBDCA) is a second generation platinum analogon and has shown comparable antitumour activity but less nephro- and neurotoxicity than cisplatin in head and neck cancer. In order to determine the feasibility and efficacy of simultaneous application of CBDCA and radiotherapy a phase I-II study is going on. Patients with advanced squamous carcinoma of the head and neck were separated into three groups which received 60 mg/m{sup 2}, 70 mg/m{sup 2} and 80 mg/m{sup 2} CBDCA from days 1 to 5 and 28 to 32. Radiotherapy was administrated up to a target absorbed dose of 70 Gy, 5x2 Gy/week in shrinking field technique. The group which received 80 mg/m{sup 2} CBDCA reached the myelotoxicity limit so that subsequent patients were treated with 70 mg/m{sup 2}. Among 30 patients who completed the treatment, 22 showed a complete (CR) and eight a partial remission (PR). (orig./MG).

  15. 47 CFR 61.136 - Revocation of concurrences.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Revocation of concurrences. 61.136 Section 61...) TARIFFS Concurrences § 61.136 Revocation of concurrences. A concurrence may be revoked by a revocation notice or cancelled by a new concurrence. A revocation notice or a new concurrence, if less broad...

  16. Cyclooxygenase Inhibitor Associated with Carboplatin in Treatment of Metastatic Nasal Carcinoma in Dog

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Fonseca-Alves

    2014-01-01

    Full Text Available A 10-year-old, intact male, pinscher was presented with unilateral bloodstained nasal discharge, sneezing, dyspnea, zygomatic arch deformity, submandibular lymph node increase, blindness in right eye, and exophthalmia. After clinical examination, it was found that the animal presented with upper respiratory tract dyspnea origin, possibly caused by an obstructive process. Complete blood count (CBC, ocular ultrasonography, thoracic radiographs, mandibular lymph node, and nasal sinus fine needle aspiration were performed. The right mandibular lymph node excisional biopsy was conducted and a tumor sample was obtained through the nasal fistula at hard palate. The material was processed, paraffin embedded, sectioned, and stained with hematoxylin and eosin. Immunohistochemical staining for cytokeratin (AE1/AE3, vimentin, and COX-2 was performed. After histopathological evaluation nasal carcinoma diagnosis was obtained. Chemotherapy was established with carboplatin 300 mg/m2 intravenously—four cycles with intervals of 21 days—and firocoxib 5 mg/kg orally every 24 hours for 7 months. After 7 months the treatment started, the animal presented with ataxia, vocalization, hyperesthesia, and anorexia. Due the clinical condition presented, the animal owner opted for performing euthanasia. The chemotherapy protocol was effective causing the disease stagnation, minimizing the clinical signs, and extending patient survival and quality of life.

  17. Synchronous lung and gastric cancers successfully treated with carboplatin and pemetrexed: a case report

    Directory of Open Access Journals (Sweden)

    Sato Takashi

    2012-08-01

    Full Text Available Abstract Introduction Lung and gastric cancers are the first and second leading causes of death from cancer worldwide, and are especially prevalent in Eastern Asia. Relatively few reports are available in relation to the treatment and outcome of synchronous lung and gastric cancers, although there are increasing numbers of patients with these cancers. Efforts to develop more effective drugs for the treatment of synchronous cancers, without serious adverse effects, have been intensifying. Pemetrexed, a multi-targeted antifolate enzyme inhibitor, was approved by the United States Food and Drug Administration as a first-line chemotherapy for advanced non-squamous non-small cell lung cancer in 2007. Although clinical activity against several tumor types of adenocarcinoma, including gastric cancer, has been demonstrated, the efficacy of pemetrexed for gastric cancer remains to be fully evaluated. Case presentation We report a case involving a 62-year-old Japanese woman with synchronous locally-advanced poorly-differentiated lung adenocarcinoma and poorly-differentiated gastric adenocarcinoma, containing signet-ring cells distinguished by immunohistochemical profiles. She had been treated with carboplatin and pemetrexed as a first-line chemotherapy for lung cancer, and had achieved partial responses for both lung and gastric cancers. These responses led to a favorable 12-month progression-free survival after the initiation of chemotherapy, and the patient is still alive more than 33 months after diagnosis. Conclusions This case suggests a new chemotherapeutic regimen for patients with synchronous multiple primary cancers that have an adenocarcinoma background.

  18. Bortezomib, Ifosfamide, Carboplatin, and Etoposide in a Patient with HIV-Negative Relapsed Plasmablastic Lymphoma

    Directory of Open Access Journals (Sweden)

    Mehmet Akce

    2016-01-01

    Full Text Available Plasmablastic lymphoma (PBL is a rare subtype of diffuse large B cell lymphoma (DLBCL, often associated with HIV infection. We present a case of a 53-year-old HIV-negative man with untreated hepatitis C viral infection who presented with abdominal pain and lymphadenopathy. Lymph node and bone marrow biopsies were consistent with plasmablastic lymphoma. He had partial response (PR to 6 cycles of EPOCH but disease progressed seven weeks later. Repeat biopsy was consistent with plasmablastic lymphoma. Three cycles of bortezomib, ifosfamide, carboplatin, and etoposide (B-ICE chemotherapy resulted in a partial response (PR. Five months later, he presented with widespread lymphadenopathy and tumor lysis syndrome with circulating blasts. Flow cytometry revealed a different population of lymphoma cells, this time positive for CD5, CD19, CD20, and CD22, with dim expression of CD45 and CD38. The patient died on the first day of ESHAP chemotherapy. There are no treatment recommendations or standard of care for plasmablastic lymphoma. A literature search yielded 10 cases in which bortezomib was administered in either HIV-positive or HIV-negative PBL. Six reported a partial response, 3 reported a complete response, and 1 was a near-complete response. Bortezomib, in combination with chemotherapy, may be an effective treatment option in PBL as reported here.

  19. Concurrent Process Planning for Machined Parts

    Institute of Scientific and Technical Information of China (English)

    吴丹; 王先逵; 李志忠

    2002-01-01

    Detailed manufacturing information about the parts can help designers produce better designs. Detailed manufacturing information is conveyed to the designer through micro-circles within the concurrent design process for machined parts, focusing on instantaneous product design and process planning. The process has three key elements: a hierarchical architecture design of the concurrent process planning system, modeling and reengineering of the concurrent process planning, and modeling of information. The approach is successfully implemented and applied for concurrent design and process planning of some complicated parts.

  20. Automated Concurrent Blackboard System Generation in C++

    Science.gov (United States)

    Kaplan, J. A.; McManus, J. W.; Bynum, W. L.

    1999-01-01

    In his 1992 Ph.D. thesis, "Design and Analysis Techniques for Concurrent Blackboard Systems", John McManus defined several performance metrics for concurrent blackboard systems and developed a suite of tools for creating and analyzing such systems. These tools allow a user to analyze a concurrent blackboard system design and predict the performance of the system before any code is written. The design can be modified until simulated performance is satisfactory. Then, the code generator can be invoked to generate automatically all of the code required for the concurrent blackboard system except for the code implementing the functionality of each knowledge source. We have completed the port of the source code generator and a simulator for a concurrent blackboard system. The source code generator generates the necessary C++ source code to implement the concurrent blackboard system using Parallel Virtual Machine (PVM) running on a heterogeneous network of UNIX(trademark) workstations. The concurrent blackboard simulator uses the blackboard specification file to predict the performance of the concurrent blackboard design. The only part of the source code for the concurrent blackboard system that the user must supply is the code implementing the functionality of the knowledge sources.

  1. A Reference Framework for Concurrent Engineering

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Considering the diversity of methods and tools offered to concurrent engineering, the aspects playing important roles in the concurrent engineering c ontext have been pinpointed as being four core elements which are Activity, Meth od, Object and Information. Based on these four elements, a reference framework called AMOI is proposed to be the guideline for the systematic concurrent produc t design. Using the AMOI reference framework, concurrent product development sys tem can be structured into four function models (including the activity model, m ethod model, object model and information model) which are interconnected with e ach other.

  2. Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Gupta, Divya; Holcomb, Kevin; Caputo, Thomas [Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Chao, K. S. Clifford; Nori, Dattatreyudu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Wernicke, A. Gabriella, E-mail: gaw9006@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States)

    2013-11-15

    Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

  3. Role of carboplatin in multi-modality treatment of canine tonsillar squamous cell carcinoma--a case series of five dogs.

    Science.gov (United States)

    Murphy, S; Hayes, A; Adams, V; Maglennon, G; Neath, P; Ladlow, J; Brearley, M J

    2006-04-01

    Canine tonsillar squamous cell carcinoma is an aggressive disease with a poor prognosis. A retrospective study was undertaken of all dogs that were presented between January 1999 and January 2004 to the Animal Health Trust for the treatment of tonsillar squamous cell carcinoma. Five cases were identified, and their median survival time was 211 days (95 per cent confidence interval 80 to 352) with two of the five dogs remaining alive at the end of the study, 826 and 1628 days from diagnosis with no clinical signs of disease. The protocol was well tolerated with only one of the five dogs showing toxicity associated with carboplatin and all dogs that started radiotherapy completing it. Compared with results of previous studies, these cases suggest that surgical cytoreduction followed by coarse fractionated radiotherapy together with carboplatin may be a useful way to treat this tumour. Carboplatin alone caused partial remission in the two cases where it was used as neo-adjunctive therapy.

  4. Imaging of treatment response to the combination of carboplatin and paclitaxel in human ovarian cancer xenograft tumors in mice using FDG and FLT PET

    DEFF Research Database (Denmark)

    Munk Jensen, Mette; Erichsen, Kamille Dumong; Björkling, Fredrik

    2013-01-01

    A combination of carboplatin and paclitaxel is often used as first line chemotherapy for treatment of ovarian cancer. Therefore the use of imaging biomarkers early after initiation of treatment to determine treatment sensitivity would be valuable in order to identify responders from non-responder......A combination of carboplatin and paclitaxel is often used as first line chemotherapy for treatment of ovarian cancer. Therefore the use of imaging biomarkers early after initiation of treatment to determine treatment sensitivity would be valuable in order to identify responders from non......-responders. In this study we describe the non-invasive PET imaging of glucose uptake and cell proliferation using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) for early assessment of treatment response in a pre-clinical mouse model of human ovarian cancer treated with carboplatin...

  5. A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia.

    Science.gov (United States)

    Pratz, Keith W; Rudek, Michelle A; Gojo, Ivana; Litzow, Mark R; McDevitt, Michael A; Ji, Jiuping; Karnitz, Larry M; Herman, James G; Kinders, Robert J; Smith, B Douglas; Gore, Steven D; Carraway, Hetty E; Showel, Margaret M; Gladstone, Douglas E; Levis, Mark J; Tsai, Hua-Ling; Rosner, Gary; Chen, Alice; Kaufmann, Scott H; Karp, Judith E

    2017-02-15

    Purpose: The PARP inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone.Experimental Design: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPN), and chronic myelomonocytic leukemia (CMML).Results: A total of 99 patients received veliparib 10-100 mg orally twice daily on days 1-8, 1-14, or 1-21 along with continuous infusion topotecan 1.0-1.2 mg/m(2)/d + carboplatin 120-150 mg/m(2)/d on days 3-7. The MTD was veliparib 80 mg twice daily for up to 21 days with topotecan 1.2 mg/m(2)/d + carboplatin 150 mg/m(2)/d. Mucositis was dose limiting and correlated with high veliparib concentrations. The response rate was 33% overall (33/99: 14 CR, 11 CRi, 8 PR) but was 64% (14/22) for patients with antecedent or associated aggressive MPNs or CMML. Leukemias with baseline DNA repair defects, as evidenced by impaired DNA damage-induced FANCD2 monoubiquitination, had improved survival [HR = 0.56 (95% confidence interval, 0.27-0.92)]. A single 80-mg dose of veliparib, as well as veliparib in combination with topotecan + carboplatin, induced DNA damage as manifested by histone H2AX phosphorylation in CD34(+) leukemia cells, with greater phosphorylation in cells from responders.Conclusions: The veliparib/topotecan/carboplatin combination warrants further investigation, particularly in patients with aggressive MPNs, CMML, and MPN- or CMML-related acute leukemias. Clin Cancer Res; 23(4); 899-907. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

    Directory of Open Access Journals (Sweden)

    Fuoco Gilda

    2011-05-01

    Full Text Available Abstract Background Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients. Methods Patients were administered oral celecoxib (400 mg/day in combination with intravenous carboplatin (AUC5, q28. A Simon's two-stage design was employed. Results 45 patients were enrolled: 23 (51.1% presented platinum-resistance, and 27 (60% had received at least 3 prior regimens for recurrence. The response rate was 28.9% with 3 complete and 10 partial responses (median duration of response = 6 months. Only one (0.4% G4 non-febrile neutropenia was observed; G3 neutropenia, anemia, or thrombocytopenia, were observed in 2.5%, 1.7%, and 1.7% of the cycles, respectively. G3-4 vomiting was reported in only 1.7%, and 0.4% of the cycles were associated with G3 dyspepsia or diarrhea or constipation. Only one patient experienced G3 hypertension associated to G2 hypersensitivity reaction. No differences in baseline versus post-treatment Quality of Life scores were observed. Median progression free survival and overall survival were 5 and 13 months, respectively. Conclusions Celecoxib combined with carboplatin showed promising activity and it is well tolerated in heavily-treated recurrent ovarian cancer patients. Trial registration number NCT01124435 (ClinicalTrials.gov Identifier and 935/03 (study ID numbers.

  7. Cost-effectiveness analysis of paclitaxel + carboplatin vs. alternative combinations in the treatment of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Mario Eandi

    2006-06-01

    Full Text Available Non-small cell lung cancer (NSCLC is the most common type of lung cancer and its medical and economical burden represents a serious matter in Europe and Usa, due to its high mortality rates and drug costs. Lung cancer is responsible for about 30% of cancer death in men and women; in Europe only about 8 per cent of people with lung cancer survive for 5 years. At present combination chemotherapy based on cisplatin or carboplatin associated with paclitaxel, vinorelbine or gemcitabine is the state of the art for the treatment in patients with stage IIIb or IV NSCLC. Aim of this study was to compare the cost-effectiveness of paclitaxel/carboplatin (PCb, gemcitabine/cisplatin (GC and vinorelbine/cisplatin (VC in the perspective of the Italian National Health Service. Therefore we perfomed a semi-Markov decision model mainly based on clinical results from the Italian Lung Cancer Project. The model included differential direct medical costs registered for two years from starting chemotherapy, using tariffs valid for 2005. Benefits was measured by years of life saved (YOLs. The model also allowed to estimate only costs accrued over the period of time, performing a cost-minimisation analysis. According to cost-effectiveness analysis, VC is dominated because it’s more costly and less effective than GC. On the contrary, combination chemotherapy with GC is more inexpensive but less effective than paclitaxel/carboplatin (PCb: in this case we compared the incremental cost-effectiveness ratio (ICER with a maximum acceptable willingness-to-pay (WTP value. In the base scenario the ICER of PCb over GC treatment is 52,326 euro/ YOLs, which is definitely lower than the maximum acceptable WTP value. Sensitivity analyses confirmed the robustness of the results from cost-effectiveness analysis in the base scenario.

  8. Concurrent partnerships and HIV: an inconvenient truth

    Directory of Open Access Journals (Sweden)

    Epstein Helen

    2011-03-01

    Full Text Available Abstract The strength of the evidence linking concurrency to HIV epidemic severity in southern and eastern Africa led the Joint United Nations Programme on HIV/AIDS and the Southern African Development Community in 2006 to conclude that high rates of concurrent sexual partnerships, combined with low rates of male circumcision and infrequent condom use, are major drivers of the AIDS epidemic in southern Africa. In a recent article in the Journal of the International AIDS Society, Larry Sawers and Eileen Stillwaggon attempt to challenge the evidence for the importance of concurrency and call for an end to research on the topic. However, their "systematic review of the evidence" is not an accurate summary of the research on concurrent partnerships and HIV, and it contains factual errors concerning the measurement and mathematical modelling of concurrency. Practical prevention-oriented research on concurrency is only just beginning. Most interventions to raise awareness about the risks of concurrency are less than two years old; few evaluations and no randomized-controlled trials of these programmes have been conducted. Determining whether these interventions can help people better assess their own risks and take steps to reduce them remains an important task for research. This kind of research is indeed the only way to obtain conclusive evidence on the role of concurrency, the programmes needed for effective prevention, the willingness of people to change behaviour, and the obstacles to change.

  9. Petri nets and other models of concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Sassone, Vladimiro

    1998-01-01

    This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency.......This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency....

  10. Safety and Liveness in Concurrent Pointer Programs

    NARCIS (Netherlands)

    Distefano, Dino; Katoen, Joost-Pieter; Rensink, Arend; Boer, de Frank S.; Bonsangue, Marcello M.; Graf, Susanne; Roever, de Willem-Paul

    2006-01-01

    The incorrect use of pointers is one of the most common source of software errors. Concurrency has a similar characteristic. Proving the correctness of concurrent pointer manipulating programs, let alone algorithmically, is a highly non-trivial task. This paper proposes an automated verification tec

  11. Steps in Modular Specifications for Concurrent Modules

    DEFF Research Database (Denmark)

    Da Rocha Pinto, Pedro; Dinsdale-Young, Thomas; Gardner, Philippa

    2015-01-01

    The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent module...

  12. Concurrent sourcing and external supplier opportunism

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    When a firm simultaneously makes and buys the same components then the firm uses concurrent sourcing. This paper presents an agency model for explaining how and when concurrent sourcing reduces the likelihood of external supplier opportunism. In the proposed model, the external supplier’s expected...

  13. Interval-based Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Løvengreen, Hans Henrik; Sørensen, Morten U.

    1998-01-01

    We propose a logic for specifying the behaviour of concurrent objects, ie. concurrent entities that invoke operation of each other. The logic is an interval logic whith operation invocatins as primitive formulas. The strengths and deficiencies of the logic are illustrated by specifying a variety...

  14. A Temporal Concurrent Constraint Programming Calculus

    DEFF Research Database (Denmark)

    Palamidessi, Catuscia; Valencia Posso, Frank Darwin

    2001-01-01

    The tcc model is a formalism for reactive concurrent constraint programming. In this paper we propose a model of temporal concurrent constraint programming which adds to tcc the capability of modeling asynchronous and non-deterministic timed behavior. We call this tcc extension the ntcc calculus...

  15. Lower Bounds of Concurrence for Multipartite States

    CERN Document Server

    Zhu, Xue-Na; Fei, Shao-Ming

    2012-01-01

    We study the entanglement of multipartite quantum states. Some lower bounds of the multipartite concurrence are reviewed. We further present more effective lower bounds for detecting and qualifying entanglement, by establishing functional relations between the concurrence and the generalized partial transpositions of the multipartite systems.

  16. New concurrent iterative methods with monotonic convergence

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Qingchuan [Michigan State Univ., East Lansing, MI (United States)

    1996-12-31

    This paper proposes the new concurrent iterative methods without using any derivatives for finding all zeros of polynomials simultaneously. The new methods are of monotonic convergence for both simple and multiple real-zeros of polynomials and are quadratically convergent. The corresponding accelerated concurrent iterative methods are obtained too. The new methods are good candidates for the application in solving symmetric eigenproblems.

  17. A Temporal Concurrent Constraint Programming Calculus

    DEFF Research Database (Denmark)

    Palamidessi, Catuscia; Valencia Posso, Frank Darwin

    2001-01-01

    The tcc model is a formalism for reactive concurrent constraint programming. In this paper we propose a model of temporal concurrent constraint programming which adds to tcc the capability of modeling asynchronous and non-deterministic timed behavior. We call this tcc extension the ntcc calculus...

  18. Imaging of treatment response to the combination of carboplatin and paclitaxel in human ovarian cancer xenograft tumors in mice using FDG and FLT PET

    DEFF Research Database (Denmark)

    Munk Jensen, Mette; Erichsen, Kamille Dumong; Björkling, Fredrik;

    2013-01-01

    A combination of carboplatin and paclitaxel is often used as first line chemotherapy for treatment of ovarian cancer. Therefore the use of imaging biomarkers early after initiation of treatment to determine treatment sensitivity would be valuable in order to identify responders from non-responder......A combination of carboplatin and paclitaxel is often used as first line chemotherapy for treatment of ovarian cancer. Therefore the use of imaging biomarkers early after initiation of treatment to determine treatment sensitivity would be valuable in order to identify responders from non...

  19. Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC

    DEFF Research Database (Denmark)

    Jensen, Lisa Helene Toft; Østerlind, Kell Erik; Rytter, C.

    2008-01-01

    BACKGROUND: Most chemotherapeutics are administrated intravenously (iv), but some are also available in an oral (po) formulation. This study was designed with the primary objective to estimate the patients' preference for po or iv vinorelbine in combination with carboplatin for the palliative...... treatment of non-small cell lung cancer (NSCLC). Secondary aims were to evaluate toxicity, efficacy, and subjective reasons the preference. PATIENTS AND METHODS: Sixty-one patients were randomized in a cross-over trial to two cycles of carboplatin day 1 and vinorelbine day 1 and day 8 iv followed by two...

  20. Combination studies of platinum(II)-based metallointercalators with buthionine-S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin.

    Science.gov (United States)

    Garbutcheon-Singh, K Benjamin; Harper, Benjamin W J; Myers, Simon; Aldrich-Wright, Janice R

    2014-01-01

    With current chemotherapeutic treatment regimes often limited by adverse side effects, the synergistic combination of complexes with anticancer activity appears to offer a promising strategy for effective cancer treatment. This work investigates the anti-proliferative activity using a combination therapy approach where metallointercalators of the type [Pt(IL)(AL)](2+) (where IL is the intercalating ligand and AL is the ancillary ligand) are used in combination with currently approved anticancer drugs cisplatin and carboplatin and organic molecules buthionine-S,R-sulfoximine and 3-bromopyruvate. Synergistic relationships were observed, indicating a potential to decrease dose-dependent toxicity and improve therapeutic efficacy.

  1. Sequential Therapy with Gemcitabine and Carboplatin Followed by Paclitaxel as First Line Treatment for Advanced Urothelial Cancer

    Directory of Open Access Journals (Sweden)

    Joseph G Kattan, Celine Y Boutros, Fadi S Farhat, Georges Y Chahine, Khaled M Musallam, Marwan G Ghosn

    2012-01-01

    Full Text Available Objective: Gemcitabine and platinum-based compounds represent the new standard combination therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gemcitabine and carboplatin followed sequentially by paclitaxel in 27 patients with advanced transitional cell carcinoma.Methods: This phase II multicentre study was based on the doublet gemcitabine 800 mg/m2 and carboplatin area under the concentration-time curve 2 on days 1 and 8 every 21 days for 4 cycles, followed sequentially by paclitaxel 60 mg/m2/w for 12 consecutive weeks. The disease was assessed after each sequence.Results: Primary tumor was localized in the bladder and renal pelvis in 25 and 2 patients, respectively. Twenty patients completed all 4 cycles of the gemcitabine and carboplatin sequence. Mean number of cycles was 3.5 (range 1 to 4. Toxicities were mainly hematologic, including Grade 3 neutropenia and anemia in 3 patients. Objective response was noted in 11 pts (40.7%, including 1 complete response (CR and 10 partial responses (PR. Three patients had stable disease and 11 progressed. Among the 20 patients, 14 received the second sequence. Mean number of paclitaxel injections was 7 (range 2 to 12. Toxicities were limited to diarrhea and neurotoxicity in 1 patient each. Objective response was documented in 6 patients (30% (3 CR and 3 PR, including the improvement of PR into CR in 2 patients. Median duration of response was 6 months. After a median follow-up of 7 months, 21 patients died and 6 remained alive, including 2 who maintained CR and 1 PR.Sixteen patients had locally advanced disease and 11 had metastatic disease, better prognostic was noticed with patients with locally advanced disease.Conclusion: the sequential approach of treatment for advanced urothelial cancer using gemcitabine and carboplatine followed by paclitaxel seems to be a safer alternative to the combined triplet, but due to the limited number of patients this study failed to improve

  2. Gaudi components for concurrency: Concurrency for existing and future experiments

    Science.gov (United States)

    Clemencic, M.; Funke, D.; Hegner, B.; Mato, P.; Piparo, D.; Shapoval, I.

    2015-05-01

    HEP experiments produce enormous data sets at an ever-growing rate. To cope with the challenge posed by these data sets, experiments’ software needs to embrace all capabilities modern CPUs offer. With decreasing memory/core ratio, the one-process-per-core approach of recent years becomes less feasible. Instead, multi-threading with fine-grained parallelism needs to be exploited to benefit from memory sharing among threads. Gaudi is an experiment-independent data processing framework, used for instance by the ATLAS and LHCbexperiments at CERN's Large Hadron Collider. It has originally been designed with only sequential processing in mind. In a recent effort, the frame work has been extended to allow for multi-threaded processing. This includes components for concurrent scheduling of several algorithms - either processingthe same or multiple events, thread-safe data store access and resource management. In the sequential case, the relationships between algorithms are encoded implicitly in their pre-determined execution order. For parallel processing, these relationships need to be expressed explicitly, in order for the scheduler to be able to exploit maximum parallelism while respecting dependencies between algorithms. Therefore, means to express and automatically track these dependencies need to be provided by the framework. In this paper, we present components introduced to express and track dependencies of algorithms to deduce a precedence-constrained directed acyclic graph, which serves as basis for our algorithmically sophisticated scheduling approach for tasks with dynamic priorities. We introduce an incremental migration path for existing experiments towards parallel processing and highlight the benefits of explicit dependencies even in the sequential case, such as sanity checks and sequence optimization by graph analysis.

  3. How does concurrent sourcing affect performance?

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    2010-01-01

    Abstract Purpose – “Concurrent sourcing” is a term used by Parmigiani to describe the phenomenon where a firm simultaneously buys and makes the same good or service. The purpose of this paper is to develop propositions that suggest how concurrent sourcing affects performance. Design....../methodology/approach – Based on transaction cost, agency, neoclassical economic, knowledge-based, and resource-based theory, it is proposed to show how concurrent sourcing affects performance. Findings – The paper argues that concurrent sourcing improves performance when firms face a combination of volume uncertainty......, technological uncertainty, performance uncertainty, non-decomposability, transaction-specific investments, and strong internal and external capabilities. Research limitations/implications – The paper maps the relationships between concurrent sourcing and performance and discusses how these relationships can...

  4. Multiparty Compatibility for Concurrent Objects

    Directory of Open Access Journals (Sweden)

    Roly Perera

    2016-06-01

    Full Text Available Objects and actors are communicating state machines, offering and consuming different services at different points in their lifecycle. Two complementary challenges arise when programming such systems. When objects interact, their state machines must be "compatible", so that services are requested only when they are available. Dually, when objects refine other objects, their state machines must be "compliant", so that services are honoured whenever they are promised. In this paper we show how the idea of multiparty compatibility from the session types literature can be applied to both of these problems. We present an untyped language in which concurrent objects are checked automatically for compatibility and compliance. For simple objects, checking can be exhaustive and has the feel of a type system. More complex objects can be partially validated via test cases, leading to a methodology closer to continuous testing. Our proof-of-concept implementation is limited in some important respects, but demonstrates the potential value of the approach and the relationship to existing software development practices.

  5. The ototoxicity of carboplatin in retinoblastoma children%卡铂对视网膜母细胞瘤化疗患儿听力损伤的观察

    Institute of Scientific and Technical Information of China (English)

    崔洁; 马晓莉; 于刚; 吴倩; 金眉; 长诚玥; 赵军阳

    2011-01-01

    Objective To analyse the ototoxicity of carboplatin in retinoblastoma children during chemecotherapy with CEV methods. Design Retrospective case series. Participants 95 children (135 eyes) with retinoblastoma in Department of Ophthalmology in Beijing Children s Hospital from November 2009 to February 2011. Methods Pure-tone audiometry, distortion-product otoacoustic e- mission and auditory brainstem response were used to measure the hearing threshold of bilateral ears at 1st, 3rd, and 6th chemecothera- py respectively. Main Outcome Measures The hearing threshold of bilateral ears. Results Three children were found to have elevated hearing threshold during chemotherapy at the 3rd chemecotherapy among all the 95 patients. Two of them were back to normal hearing status in the following measurement. Only one child remained abnormal hearing threshold of his left ear up to 60 dB till the last measurement. Conclusion The ototoxicity of carboplatin during the chemecotherapy of retinoblastoma children is not common, while concurrent audiologic follow-up is required.%目的 观察卡铂在化疗过程中对视网膜母细胞瘤患儿的听力损伤及其严重程度.设计 回顾性病例系列.研究对象 选择自2009年11月至2011年2月在我院进行卡铂(carboplatin)、依托泊苷(etoposide)、长春新碱(vincristine)方案化疗的视网膜母细胞瘤患者111例,排除相关因素后95例患者(135眼)入选.方法 分别在第1、3、6次化疗前进行与年龄相匹配的听力学检查,包括纯音测听(pure-tone audiometry)检查、畸变产物耳声发射(distortion-product otoacoustic emission,DPOAE)检查、听力脑干诱发电位(auditory brainstem response,ABR)检查等.观察化疗过程中双耳听力阈值的变化情况,并判断是否有听力损害.主要指标 听力阈值.结果 进行化学治疗的平均疗程为5.4次(3~10次).化疗过程中,95例患者中仅3例出现听力检查结果的异常,其中2例在随后的复

  6. CT associated with clinical indexes to evaluate therapeutic efficacy of continuous regional intra-arterial infusion of somatostatin for treatment of severe acute pancreatitis%持续性区域动脉介入灌注生长抑素治疗重症急性胰腺炎疗效的CT与临床联合评价

    Institute of Scientific and Technical Information of China (English)

    卢嘉翰; 康振朝; 鲁福文; 张万甲; 齐钧; 庞永亮; 王伟

    2013-01-01

    Objective The purpose of the study was to adopt CT associated with clinical indexes to evaluate the therapeutic efficacy of continuous regional intra-arterial infusion(CRI) of somatostatin and antibiotics in patients of severe acute pancreatitis(SAP).Methods One hundred and twenty-one cases of SAP patients were randomly divided into two groups,CRI group with 60 cases and conventional treating group with 61 cases.In CRI group,antibiotics and somatostatins were pumped into the catheters in the bad flood supplying artery of pancreas from the catheter of femoral artery by a micro pump for 24 hours,and after the symptoms and signs of SPA patients disappeared,the catheters were moved out.In the conventional treating group, the same dose of antibiotics and somatostatins were given by intravenous infusion method.Results In SAP patients through the treatment, CRI group as compared with conventional group showed better effect,shortened the time for abdominal pain (4.9±2.3) d vs (6.3±2.1) d,abdominal tenderness (6.3± 2.1) d vs (8.8±2.9) d,hemodiastase to normal (8.7±1.9) d vs (9.5±1.6) d,and average hospitalization days (25.0± 5.3) d vs (36.0±4.2) d,and Balthazar CT grade obviously decreased.Conclusion CRI of somatostatin for the treatment of SAP confirms the therapeutic efficacy as an ideal treatment.%目的 CT联合临床指标评价持续性区域动脉介入灌注生长抑素治疗重症急性胰腺炎(SAP)的疗效.方法 121例患者随机分为持续性区域灌注(CRI)组(60例)和常规给药组(61例),区域灌注组经股动脉超选择插管至胰腺坏死的供血动脉留置导管,用微泵持续24小时灌注生长抑素及抗生紊,症状体征消失后拔管.常规给药组用静脉输注药物,药物剂量完全同区域灌注组.结果 SAP患者经过治疗,CRI组与常规给药组比较疗效显著,临床指标恢复时间缩短,腹痛症状消失时间(4.9±2.3)d vs (6.3±2.1)d、腹压痛消失时间(6.3±2.1) dvs(8.8±2.9)d、

  7. Retrospective study on glucose metabolism disorders induced by preoperative intra-arterial infusion chemotherapy with EOF regimen in patients with gastric cancer%EOF 方案术前动脉介入化疗对胃癌患者血糖影响的回顾性研究

    Institute of Scientific and Technical Information of China (English)

    王兆京; 陈彻; 陈志伟; 姚学权; 刘福坤

    2015-01-01

    目的:探讨胃癌患者接受EOF方案术前动脉介入化疗前后血糖水平的变化,并分析相关因素对血糖变化的影响。方法:收集2012年至2014年间92例接受EOF方案术前动脉介入化疗的胃癌患者在介入化疗前及介入化疗后24 h的空腹血糖检验结果及相关临床资料,进行回顾性分析。结果:EOF方案动脉介入化疗后患者血糖平均水平增加,与介入化疗前相比差异有统计学意义( P<0.01)。患者年龄、性别、肿瘤部位、肿瘤分期等相关因素对血糖升高的影响差异无统计学意义( P>0.05)。合并糖尿病的胃癌患者动脉介入化疗后血糖升高水平明显高于非糖尿病患者,差异有统计学意义( P<0.001)。结论:EOF方案动脉介入化疗可使胃癌患者的血糖升高,尤其是合并糖尿病的胃癌患者血糖升高尤为明显,在积极治疗原发病的同时应注意监测患者血糖并及时处理。%Objective:To explore the effects of the preoperative intra-arterial infusion chemotherapy( PAIC) with EOF regimen on blood glucose of gastric cancer patients and to find the influencing factors.Methods:92 patients with gastric cancer participated in the study; they had received PAIC from 2012 to 2014 in our hospital.The regimen consisted of EPI 50 mg · m-2 , OXA 130 mg · m-2 , and 5-FU 750 mg · m-2 .Their blood glucose was detected on schedule before and after chemotherapy; clinical factors were collected.Some changed regularity on blood glucose and the influential factors were found after chemotherapy.Results: After PAIC, patients'blood glucose was higher than before the treatment ( P0.05 ) .Gastric cancer patients with diabetes were more vulnerable to induce blood glucose rose after PAIC( P<0.001) .Conclusion:PAIC could enhance blood glucose level in gastric cancer patients, especially in patients with diabetes mellitus.In order to complete tumor chemotherapy safely and successfully, strict

  8. Comparison of contrast-enhanced MR angiography of the aortoiliac vessels using a 1.0 molar contrast agent at 1.0T with intra-arterial digital subtraction angiography; Ergebnisse der kontrastverstaerkten MR-Angiographie der aortoiliakalen Gefaesse mit einem 1-molaren Kontrastmittel bei 1,0 T; Vergleich zur i.a. DSA

    Energy Technology Data Exchange (ETDEWEB)

    Mohrs, O.K. [Klinik und Poliklinik fuer Radiologie, Johannes Gutenberg-Univ. Mainz (Germany); Cardioangiologisches Centrum Bethanien, Frankfurt/Main (Germany); Oberholzer, K.; Bernhard, S.; Kalden, P.; Thelen, M.; Kreitner, K.F. [Klinik und Poliklinik fuer Radiologie, Johannes Gutenberg-Univ. Mainz (Germany); Krummenauer, F. [Inst. fuer Med. Biometrie, Epidemiologie und Informatik, Johannes Gutenberg-Univ. Mainz (Germany); Neufang, A. [Klinik fuer Herz- und Thoraxchirurgie, Johannes Gutenberg-Univ. Mainz (Germany)

    2004-07-01

    Purpose: To evaluate the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) using a 1.0 molar contrast agent at 1.0 T for the diagnosis of abdominal aortic aneurysms and stenoses of renal or iliac arteries in comparison to intraarterial digital subtraction angiography (DSA). Materials and Methods: A total of 19 patients with the suspicion of abdominal aortic aneurysm or stenosis of renal or iliac arteries were examined with CE-MRA at 1.0 T. Intra-arterial DAS served as reference in all cases. After test bolus tracking, 10 or 8 ml of the 1.0 molar contrast agent Gadobutrol corresponding to a dose of 0.1-0.15 mmol/kg bw were injected and imaging performed using a FLASH-3D sequence. To evaluate the interobserver-variability, the blinded images were analyzed by two radiologists. Besides the rating of overall image quality on a 4-point-scale, the images were evaluated for aneurysms and arteriosclerotic lesions with a stenosis of < 50% or > 50% or occlusion. Results: A total of 144 segments were analyzed. The mean value of the CE-MRA image quality was 3.4 on a 4-point scale. The sensitivity of CE-MRA in depicting relevant pathological findings was 96% and the specifity 99%. The positive predictive value was 96% and the negative predictive value 99%. Inter-observer variability was low with a kappa value of 0.82. Conclusion: CE-MRA using a 1.0 molar contrast agent at 1.0 Tenables an excellent diagnosis or exclusion of pathologies of the aortoiliac vessels. (orig.) [German] Ziel: Vergleich der MR-Angiographie (ce-MRA) der aortoiliakalen Gefaesse unter Verwendung eines 1-molaren, paramagnetischen Kontrastmittels bei 1,0 T zur intraarteriellen digitalen Subtraktionsangiographie (i.a. DSA). Material und Methoden: Es wurden 19 Patienten mit Verdacht auf ein infrarenales Aortenaneurysma bzw. eine Stenose der Nieren- oder Iliakalarterien untersucht. Die Messungen erfolgten bei 1,0 T unter Verwendung des 1-molaren, paramagnetischen Kontrastmittels Gadobutrol

  9. Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer-bearing dogs.

    Science.gov (United States)

    Allstadt Frazier, S; McKemie, D S; Guerrero, T A; LaChapelle, H; Skorupski, K A; Kass, P H; Rodriguez, C O

    2014-03-01

    Rosiglitazone is an FDA-approved peroxisome proliferator-activated receptor gamma (PPARγ) agonist and antidiabetic agent in humans that has been investigated for its ability to reduce tumor cell growth. The purpose of this study was to determine the maximally tolerated dose, peak plasma concentrations and side effect profile of oral rosiglitazone when combined with carboplatin in dogs with cancer. Rosiglitazone was administered at 6 and 8 mg/m(2) to seven dogs. Carboplatin was administered at 240-300 mg/m(2) in combination with rosiglitazone. For toxicity evaluation, the toxicity data for the seven dogs in this study were combined with the toxicity data from three dogs previously reported in a methodology study. Peak plasma rosiglitazone concentrations varied with dose. The dose-limiting toxicity was hepatic at a dose of 8 mg/m(2). Three dogs had mild to moderate alanine aminotransferase elevations but no changes in total bilirubin, alkaline phosphatase, blood glucose or γ-glutamyltranspeptidase values were noted.

  10. Automatic and Hierarchical Verification for Concurrent Systems

    Institute of Scientific and Technical Information of China (English)

    赵旭东; 冯玉琳

    1990-01-01

    Proving correctness of concurrent systems is quite difficult because of the high level of nondeterminism,especially in large and complex ones.AMC is a model checking system for verifying asynchronous concurrent systems by using branching time temporal logic.This paper introduces the techniques of the modelling approach,especially how to construct models for large concurrent systems with the concept of hierarchy,which has been proved to be effective and practical in verifying large systems without a large growth of cost.

  11. Concurrent Manipulation of Expanded AVL Trees

    Institute of Scientific and Technical Information of China (English)

    章寅; 许卓群

    1998-01-01

    The concurrent manipulation of an expanded AVL tree(EAVL tree)s considered in this paper.The presented system can support any number of concurrent processes which perform searching,insertion and deletion on the tree.Simulation results indicate the high performance of the system.Elaborate techniques are used to achieve such a system unavailable based on any known algorithms.Methods developed in this paper may provide new insights into other problems in the area of concurrent search structure manipulation.

  12. Adjuvant docetaxel and carboplatin chemotherapy administered alone or with radiotherapy in a "sandwich" protocol in patients with advanced endometrial cancer: a single-institution experience.

    Science.gov (United States)

    Lan, Chunyan; Huang, Xin; Cao, Xinping; Huang, He; Feng, Yanling; Huang, Yongwen; Liu, Jihong

    2013-04-01

    To evaluate the outcomes of adjuvant chemotherapy administered alone or with radiotherapy in a "sandwich" protocol in patients with advanced endometrial cancer. The authors retrospectively reviewed the clinical records of patients with staged III - IV disease who received adjuvant chemotherapy (docetaxel plus carboplatin) administered alone or interposed with radiotherapy between January 2004 and August 2010. Of the 35 study patients, 10 (28.6%) had stage IIIA disease, 15 (42.9%) had IIIC1 disease, 7 (20.0%) had IIIC2 disease and 3 (8.6%) had IVB disease. Nine (90.0%) of the 10 patients with stage IIIA disease received four to six cycles of adjuvant docetaxel and carboplatin chemotherapy alone. All 25 patients with stage IIIC - IVB disease and 1 patient with stage IIIA disease received radiotherapy sandwiched between chemotherapy cycles (total, three to six cycles). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 73.0 and 87.0%, respectively, for all patients. For patients with stage IIIC - IVB disease, the 3-year PFS and OS rates were 62.4 and 81.8%, respectively. Combination chemotherapy with docetaxel and carboplatin interposed with radiotherapy is efficacious and well tolerated for stage IIIC - IVB endometrial cancer. Adjuvant chemotherapy alone with docetaxel and carboplatin might be sufficient for stage IIIA disease.

  13. Paclitaxel and carboplatin in the treatment of small-cell lung cancer patients resistant to cyclophosphamide, doxorubicin, and etoposide : A non-cross-resistant schedule

    NARCIS (Netherlands)

    Groen, HJM; Fokkema, E; Biesma, B; Kwa, B; van Putten, JWG; Postmus, PE; Smit, EF

    1999-01-01

    Purpose: To evaluate the efficacy of paclitaxel and carboplatin (PC) in small-cell lung cancer (SCLC) patients resistant to cyclophasphamide, doxorubicin, and etoposide (CDE). Patients and Methods: We performed a phase II study with PC in SCLC patients who relapsed within 3 months after first-line t

  14. Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site

    DEFF Research Database (Denmark)

    Hainsworth, John D; Daugaard, Gedske; Lesimple, Thierry

    2015-01-01

    BACKGROUND: The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first-line treatment of patients with carcinoma of unknown primary site (CUP). METHODS: In this randomized phase 2 trial, previo...

  15. Randomized Phase II and Pharmacogenetic Study of Pemetrexed Compared With Pemetrexed Plus Carboplatin in Pretreated Patients With Advanced Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Smit, Egbert F.; Burgers, Sjaak A.; Biesma, Bonne; Eppinga, Pier; Dingemans, Anne-Marie C.; Joerger, Markus; Schellens, Jan H.; Vincent, Andrew; van Zandwijk, Nico; Groen, Harry J. M.

    2009-01-01

    Purpose We performed a randomized phase II trial comparing pemetrexed with pemetrexed plus carboplatin (PC) in patients experiencing relapse after platinum-based chemotherapy. Patients and Methods Main eligibility criteria were histologic or cytologic proof of advanced non-small-cell lung cancer (NS

  16. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage      I seminoma: a randomised trial

    DEFF Research Database (Denmark)

    Oliver, R. T. D.; Mason, M. D.; Mead, G. M.;

    2005-01-01

    BACKGROUND: Adjuvant radiotherapy is effective treatment for stage I       seminoma, but is associated with a risk of late non-germ-cell cancer and       cardiovascular events. After good results in initial studies with one       injection of carboplatin, we undertook a large randomised trial to ...

  17. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  18. Similarity based mixed transaction concurrency control protocol

    Institute of Scientific and Technical Information of China (English)

    PAN Yi; LU Yan-sheng

    2005-01-01

    Due to the various performance requirements and data access restrictions of different types of real-time transactions, concurrency control protocols which had been designed for the systems with single type of transactions are not sufficient for mixed real-time database systems (MRTDBS), where different types of real-time transactions coexist in the systems concurrently. In this paper, a new concurrency control protocol MRTT_CC for mixed real-time transactions is proposed. The new strategy integrates with different concurrency control protocols to meet the deadline requirements of different types of real-time transactions. The data similarity concept is also explored in the new protocol to reduce the blocking time of soft real-time transactions, which increases their chances to meet the deadlines. Simulation experiments show that the new protocol has gained good performance.

  19. 33 CFR 385.7 - Concurrency statements.

    Science.gov (United States)

    2010-07-01

    ... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.7 Concurrency statements. The administrative record of the programmatic regulations in this part..., Jacksonville District, 701 San Marco Blvd., Jacksonville, Florida 32207, or by accessing the...

  20. Strategy Improvement for Concurrent Safety Games

    CERN Document Server

    Chatterjee, Krishnendu; Henzinger, Thomas A

    2008-01-01

    We consider concurrent games played on graphs. At every round of the game, each player simultaneously and independently selects a move; the moves jointly determine the transition to a successor state. Two basic objectives are the safety objective: ``stay forever in a set F of states'', and its dual, the reachability objective, ``reach a set R of states''. We present in this paper a strategy improvement algorithm for computing the value of a concurrent safety game, that is, the maximal probability with which player 1 can enforce the safety objective. The algorithm yields a sequence of player-1 strategies which ensure probabilities of winning that converge monotonically to the value of the safety game. The significance of the result is twofold. First, while strategy improvement algorithms were known for Markov decision processes and turn-based games, as well as for concurrent reachability games, this is the first strategy improvement algorithm for concurrent safety games. Second, and most importantly, the impro...

  1. Tools and Patterns for Dependable Concurrent Software

    NARCIS (Netherlands)

    Jovanovic, D.S.; Broenink, Johannes F.

    2005-01-01

    First, we give reasons for choosing a process-oriented approach for building complex concurrent systems. Upon a brief review of dependability attributes of software-supported systems, means for increasing dependability in process-oriented architectures are illustrated

  2. CilkSpec: Optimistic Concurrency for Cilk

    Energy Technology Data Exchange (ETDEWEB)

    Aga, Shaizeen D.; Krishnamoorthy, Sriram; Narayanasamy, Satish

    2015-11-15

    Recursive parallel programming models such as Cilk strive to simplify the task of parallel programming by enabling a simple divide-and-conquer model of programming. This model is effective in re- cursively partitioning work into smaller parts and combining their results. However, recursive work partitioning can impose additional constraints on concurrency than is implied by the true dependences in a program. In this paper, we present a speculation-based approach to alleviate the concurrency constraints imposed by such recursive parallel programs. We design a runtime infrastructure that supports speculative execution and a predictor to accurately learn and identify opportunities to relax extraneous concurrency constraints. Experimental evaluation demonstrates that speculative relaxation of concurrency constraints can deliver gains of up to 1.6× on 30 cores over baseline Cilk.

  3. Heterogeneous concurrent computing with exportable services

    Science.gov (United States)

    Sunderam, Vaidy

    1995-01-01

    Heterogeneous concurrent computing, based on the traditional process-oriented model, is approaching its functionality and performance limits. An alternative paradigm, based on the concept of services, supporting data driven computation, and built on a lightweight process infrastructure, is proposed to enhance the functional capabilities and the operational efficiency of heterogeneous network-based concurrent computing. TPVM is an experimental prototype system supporting exportable services, thread-based computation, and remote memory operations that is built as an extension of and an enhancement to the PVM concurrent computing system. TPVM offers a significantly different computing paradigm for network-based computing, while maintaining a close resemblance to the conventional PVM model in the interest of compatibility and ease of transition Preliminary experiences have demonstrated that the TPVM framework presents a natural yet powerful concurrent programming interface, while being capable of delivering performance improvements of upto thirty percent.

  4. Abstract Diagnosis for Timed Concurrent Constraint programs

    CERN Document Server

    Comini, Marco; Villanueva, Alicia

    2011-01-01

    The Timed Concurrent Constraint Language (tccp in short) is a concurrent logic language based on the simple but powerful concurrent constraint paradigm of Saraswat. In this paradigm, the notion of store-as-value is replaced by the notion of store-as-constraint, which introduces some differences w.r.t. other approaches to concurrency. In this paper, we provide a general framework for the debugging of tccp programs. To this end, we first present a new compact, bottom-up semantics for the language that is well suited for debugging and verification purposes in the context of reactive systems. We also provide an abstract semantics that allows us to effectively implement debugging algorithms based on abstract interpretation. Given a tccp program and a behavior specification, our debugging approach automatically detects whether the program satisfies the specification. This differs from other semiautomatic approaches to debugging and avoids the need to provide symptoms in advance. We show the efficacy of our approach...

  5. Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort.

    Science.gov (United States)

    Cathomas, R; Klingbiel, D; Geldart, T R; Mead, G M; Ellis, S; Wheater, M; Simmonds, P; Nagaraj, N; von Moos, R; Fehr, M

    2014-08-01

    Seminoma stage I is the most frequent testis cancer and single-dose carboplatin (AUC7) is an effective and widely used adjuvant treatment. Underdosing of carboplatin by 10% has been shown to almost double the rate of relapse and hence correct dosing based on accurate GFR measurement is crucial. The gold standard of GFR measurement with a radiolabelled isotope is expensive and not readily available. In many institutions, it is replaced by GFR estimation with the Cockcroft-Gault formula, which might lead to significant carboplatin underdosing and potentially inferior clinical outcome. Retrospective analysis of all patients with stage I seminoma treated with adjuvant carboplatin between 1999 and 2012. All patients had serum creatinine measured and underwent GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI, Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy. Bias, precision, rates of under- and overdosing of GFR estimates were compared with measured GFR. Bland-Altman plots were done. A total of 426 consecutive Caucasian male patients were included: median age 39 years (range 19-60 years), median measured GFR 118 ml/min (51-209), median administered carboplatin dose 1000 mg (532-1638). In comparison to isotopic GFR measurement, a relevant proportion of patients would have received ≤ 90% of carboplatin dose through the use of GFR estimation formulae: 4% using Mayo, 9% Martin, 18% Cockcroft-Gault, 24% Wright, 63% Jelliffe, 49% MDRD and 41% using CKD-EPI. The flat dosing strategy, Wright and Cockcroft-Gault formulae, showed the smallest bias with mean percentage error of +1.9, +0.4 and +2.1, respectively. Using Cockcroft-Gault or any other formula for GFR estimation leads to underdosing of adjuvant carboplatin in a relevant number of patients with Seminoma stage I and should not be regarded as standard of care. © The Author 2014. Published by Oxford

  6. Potentiating effect of UVA irradiation on anticancer activity of Carboplatin derivatives involving 7-azaindoles.

    Directory of Open Access Journals (Sweden)

    Pavel Štarha

    Full Text Available The moderate-to-high in vitro cytotoxicity against ovarian A2780 (IC50 = 4.7-14.4 μM, prostate LNCaP (IC50 = 18.7-30.8 μM and prostate PC-3 (IC50 = 17.6-42.3 μM human cancer cell lines of the platinum(II cyclobutane-1,1'-dicarboxylato complexes [Pt(cbdc(naza2] (1-6; cbdc = cyclobutane-1,1'-dicarboxylate(2-; naza = halogeno-substituted 7-azaindoles, derived from the anticancer metallodrug carboplatin, are reported. The complexes containing the chloro- and bromo-substituted 7-azaindoles (1, 2, and 4-6 showed a significantly higher (p < 0.05 cytotoxicity against A2780 cell line as compared to cisplatin used as a reference drug. Addition of the non-toxic concentration (5.0 μM of L-buthionine sulfoximine (L-BSO, an effective inhibitor of γ-glutamylcysteine synthase markedly increases the in vitro cytotoxicity of the selected complex 3 against A2780 cancer cell line by a factor of about 4.4. The cytotoxicity against A2780 and LNCaP cells, as well as the DNA platination, were effectively enhanced by UVA light irradiation (λmax = 365 nm of the complexes, with the highest phototoxicity determined for compound 3, resulting in a 4-fold decline in the A2780 cells viability from 25.1% to 6.1%. The 1H NMR and ESI-MS experiments suggested that the complexes did not interact with glutathione as well as their ability to interact with guanosine monophosphate. The studies also confirmed UVA light induced the formation of the cis [Pt(H2O2(cbdc`(naza] intermediate, where cbdc` represents monodentate-coordinated cbdc ligand, which is thought to be responsible for the enhanced cytotoxicity. This is further supported by the results of transcription mapping experiments showing that the studied complexes preferentially form the bifunctional adducts with DNA under UVA irradiation, in contrast to the formation of the less effective monofunctional adducts in dark.

  7. Inheritance and Synchronization in Concurrent OOP

    Science.gov (United States)

    Briot, Jean-Pierre; Yonezawa, Akinori

    This paper discusses knowledge sharing (inheritance) mechanisms for Object-Oriented Programming (OOP) in the context of concurrent (distributed) languages. We review three different schemes: inheritance, delegation and copy. A fourth model, called recipe-query, is presented and all are compared and criticized. Techniques relying on the shared memory assumption are rejected. We point out the conflict between distributing knowledge among objects and the synchronization of concurrent objects.

  8. A Concurrent Object-Oriented Language Ondine

    OpenAIRE

    Arisawa, Makoto; Ogihara, Takeshi; Kajihara, Yoichi

    1988-01-01

    A new concurrent object-oriented language Ondine is described. The Ondine design goals are strong information hiding within objects, concurrent programming, and pointerless programming. Ondine has ordinary control statements and types so that Ada or C programmers can easily handle it. By introducing by copy and by object assignment/argument passing, an Ondine object can be accessed from only one other object thus accomplishing pointerless structure. Ondine channels are used for constructing o...

  9. Noninterference for Concurrent Programs and Thread Systems

    OpenAIRE

    Boudol, Gérard; Castellani, Ilaria

    2001-01-01

    We propose a type system to ensure the property of noninterference in a system of concurrent programs, described in a standard imperative language enriched with parallelism. Our proposal is in the line of some recent work by Irvine, Volpano and Smith. Our type system seems more natural and less restrictive than that originally presented by these authors for the concurrent case. Moreover, we show how to extend the language in order to formalise scheduling policies for systems of sequential thr...

  10. Carboplatin plus pemetrexed offers superior cost-effectiveness compared to pemetrexed in patients with advanced non-small cell lung cancer and performance status 2.

    Science.gov (United States)

    Schluckebier, Luciene; Garay, Osvaldo U; Zukin, Mauro; Ferreira, Carlos G

    2015-09-01

    Pemetrexed plus carboplatin offers survival advantage in first line treatment of advanced lung cancer patients with performance status of 2. We estimated the cost-effectiveness of this combined regimen compared to pemetrexed alone in a Brazilian population. A cost-effectiveness analysis was conducted based on a randomized phase III trial in patients with advanced non-small cell lung cancer (NSCLC) and ECOG performance status of 2 (PS2), comparing doublet regimen pemetrexed plus carboplatin with pemetrexed alone. The perspective adopted was the public health care sector over a three-year period. Direct medical costs and survival time were calculated from patient-level data and utility values were extracted from the literature. Sensitivity analyses were performed to evaluate uncertainties in the results. The combined regimen pemetrexed plus carboplatin yielded a gain of 0.16 life year (LY) and 0.12 quality-adjusted life year (QALY) compared to pemetrexed alone. The total cost was 17,674.31 USD for the combined regimen and 15,722.39 USD for pemetrexed alone. The incremental cost-effectiveness ratio (ICER) was $12,016.09 per LY gained and $15,732.05 per QALY gained. The factors with the greatest impact on the ICER are pemetrexed price and the time to progression utility value. The cost-effectiveness acceptability curve showed an upper 90% probability of pemetrexed plus carboplatin being cost-effective with a threshold between two and three GDP per capita. Our study suggests superiority of the combined pemetrexed plus carboplatin regimen in terms of efficacy as well as cost-effectiveness in advanced NSCLC patients with a poor performance status of 2. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

    Directory of Open Access Journals (Sweden)

    Cheryl A London

    Full Text Available We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI and overall survival (OS in dogs with appendicular osteosarcoma (OSA following amputation and carboplatin chemotherapy.This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126 received carboplatin chemotherapy (4 doses following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8 were removed from the study for therapy-associated adverse events compared to control dogs (n = 1. The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274; the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08. The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.The addition of toceranib to metronomic

  12. The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells

    Science.gov (United States)

    Brozovic, Anamaria; Duran, George E.; Wang, Yan C; Francisco, E. Brian; Sikic, Branimir I.

    2015-01-01

    We studied the role of miRNA-200 family members in cellular sensitivity to paclitaxel and carboplatin, using two ovarian cancer cell lines, OVCAR-3 and MES-OV, and their paclitaxel resistant variants OVCAR-3/TP and MES-OV/TP. Both resistant variants display a strong epithelial-mesenchymal transition (EMT) phenotype, with marked decreases in expression of miR-200c and miR-141 in OVCAR-3/TP, and down-regulation of all five members of the miR-200 family in MES-OV/TP. Lentiviral transfection of inhibitors of miR-200c or miR-141 in parental OVCAR-3 triggered EMT and rendered the cells resistant to paclitaxel and carboplatin. Conversely, the infection of OVCAR-3/TP cells with retroviral particles carrying the miR-200ab429 and 200c141 clusters triggered a partial mesenchymal to epithelial transition (MET). This partial MET was not sufficient to re-sensitize OVCAR-3/TP cells to paclitaxel. However, the miR-200c/miR-141 cluster transfectants became 6-8× resistant to carboplatin, an unexpected result, whereas miR-200a/miR-200b/miR-429 had no effect. Transfecting the OVCAR-3/TP GFP cells with specific miRNA mimics confirmed these data. MiR-200c and miR-141 mimics conferred resistance to carboplatin in MES-OV/TP cells, similar to OVCAR-3/TP, but sensitized MES-OV to paclitaxel. Several genes involved in balancing oxidative stress were altered in OVCAR-3/TP 200c141 cells compared to controls. The miR-200 family plays major, cell-context dependent roles in regulating EMT and sensitivity to carboplatin and paclitaxel in OVCAR-3 and MES-OV cells. PMID:26025631

  13. Characterizing Distributed Concurrent Engineering Teams: A Descriptive Framework for Aerospace Concurrent Engineering Design Teams

    Science.gov (United States)

    Chattopadhyay, Debarati; Hihn, Jairus; Warfield, Keith

    2011-01-01

    As aerospace missions grow larger and more technically complex in the face of ever tighter budgets, it will become increasingly important to use concurrent engineering methods in the development of early conceptual designs because of their ability to facilitate rapid assessments and trades in a cost-efficient manner. To successfully accomplish these complex missions with limited funding, it is also essential to effectively leverage the strengths of individuals and teams across government, industry, academia, and international agencies by increased cooperation between organizations. As a result, the existing concurrent engineering teams will need to increasingly engage in distributed collaborative concurrent design. This paper is an extension of a recent white paper written by the Concurrent Engineering Working Group, which details the unique challenges of distributed collaborative concurrent engineering. This paper includes a short history of aerospace concurrent engineering, and defines the terms 'concurrent', 'collaborative' and 'distributed' in the context of aerospace concurrent engineering. In addition, a model for the levels of complexity of concurrent engineering teams is presented to provide a way to conceptualize information and data flow within these types of teams.

  14. IMPACT OF BEP OR CARBOPLATIN CHEMOTHERAPY ON TESTICULAR FUNCTION AND SPERM NUCLEUS OF SUBJECTS WITH TESTICULAR GERM CELL TUMOR

    Directory of Open Access Journals (Sweden)

    Marco eGhezzi

    2016-05-01

    Full Text Available Young males have testicular germ cells tumours (TGCT as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO, the treatment of TGCT may include surveillance, radiotherapy or chemotherapy (CT, basing on tumour histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide and cisplatin (BEP, after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group, 54 with carboplatin (Carb group and 58 were just surveilled (S-group. All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0 and after 12 (T1 and 24 months (T2 from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones and testicular volume at baseline were not different between groups. At T1 we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S- group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S group and Carb group. These alterations were persistent after two years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after one and two years from the end of treatment

  15. Carboplatin with Decitabine Therapy, in Recurrent Platinum Resistant Ovarian Cancer, Alters Circulating miRNAs Concentrations: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Eric A Benson

    Full Text Available Plasma miRNAs represent potential minimally invasive biomarkers to monitor and predict outcomes from chemotherapy. The primary goal of the current study-consisting of patients with recurrent, platinum-resistant ovarian cancer-was to identify the changes in circulating miRNA concentrations associated with decitabine followed by carboplatin chemotherapy treatment. A secondary goal was to associate clinical response with changes in circulating miRNA concentration.We measured miRNA concentrations in plasma samples from 14 patients with platinum-resistant, recurrent ovarian cancer enrolled in a phase II clinical trial that were treated with a low dose of the hypomethylating agent (HMA decitabine for 5 days followed by carboplatin on day 8. The primary endpoint was to determine chemotherapy-associated changes in plasma miRNA concentrations. The secondary endpoint was to correlate miRNA changes with clinical response as measured by progression free survival (PFS.Seventy-eight miRNA plasma concentrations were measured at baseline (before treatment and at the end of the first cycle of treatment (day 29. Of these, 10 miRNAs (miR-193a-5p, miR-375, miR-339-3p, miR-340-5p, miR-532-3p, miR-133a-3p, miR-25-3p, miR-10a-5p, miR-616-5p, and miR-148b-5p displayed fold changes in concentration ranging from -2.9 to 4 (p<0.05, in recurrent platinum resistant ovarian cancer patients, that were associated with response to decitabine followed by carboplatin chemotherapy. Furthermore, lower concentrations of miR-148b-5p after this chemotherapy regimen were associated (P<0.05 with the PFS.This is the first report demonstrating altered circulating miRNA concentrations following a combination platinum plus HMA chemotherapy regiment. In addition, circulating miR-148b-5p concentrations were associated with PFS and may represent a novel biomarker of therapeutic response, with this chemotherapy regimen, in women with recurrent, drug-resistant ovarian cancer.

  16. 经动脉灌注脂肪乳剂顺铂混合液行犬胰腺癌局部化疗的研究%Regional intra-arterial infusion chemotherapy for pancreatic cancer of dogs with the mixture of lipid emulsion-cisplatin:an experimental study

    Institute of Scientific and Technical Information of China (English)

    李强; 王茂强; 段留新; 宋鹏; 敖国昆; 廖洪波; 宋晶莹

    2009-01-01

    P值均<0.01));B组的AUC、C0明显低于A组(t值分别为7.57、5.48,P值均<0.01),t1/2长于A组(t值为3.22,P<0.05)。 B组的胰左叶、胰腺角中顺铂含量较A组增高[B组分别为0.18、0.18 mg/L,A组分别为0.05、0.05 mg/L],差异有统计学意义( t值分别为2.52、2.73,P值均<0.05);胰腺右叶和脾脏组织中的顺铂浓度两组比较差异无统计学意义[B组分别为0.11、0.29 mg/L,A组分别为0.07、0.24 mg/L,P值均>0.05]。病理检查所见:A、B组犬胰腺、胰周淋巴结、肝脏、脾脏有少量炎细胞浸润及血管扩张充血,血管内可见脂肪乳颗粒。其余组织及C、D组病理检查未见异常。结论脂肪乳作为溶剂可使顺铂在胰腺的浓度显著增高、进入血循环的药物总量减少。进入组织的药物量与脂肪乳内所含顺铂的浓度有关,浓度越高,进入组织内的药物越多。%Objective To approach the mechanism and efficacy of regional intra-arterial infusion chemotherapy with the mixture of lipid emulsion-CDDP ( LE-CDDP ) for treatment of locally advanced pancreatic cancer.Methods Twenty-four health dogs were divided into four groups ( group A,B,C, and D).The dosage of CDDP was used in 4 mg/kg/body weight for each animal.The 20%LE, as a solvent, was used in the experimental animals with 2 ml/kg/body weight ( group A ) and 1 ml/kg/body weight ( group B) , respectively.Normal sodium ( NS) as a solvent was used as control with 2 ml/kg/body weight (group C) and 1 ml/kg/body weight (group D), respectively.The LE-CDDP mixture and the NS-CDDP mixture were infused into the proximal segment of splenic artery under the DSA, with transfemoral arterial approach.Blood samples were collected after infusion at 0,3,5,10,20,30,40,50,60 min and the tissues were obtained after the 60 min′s blood sample was collected.Blood samples, absorbent gland in peripancreas, liver, spleen, kidney

  17. Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up

    DEFF Research Database (Denmark)

    Lassen, U; Kristjansen, P E; Osterlind, K

    1996-01-01

    PURPOSE: The introduction of platinum compounds and epipodophyllotoxins in combination with vincristine as induction chemotherapy in small-cell lung cancer (SCLC) was investigated in order to: (1) compare the efficacy of cisplatin with that of carboplatin in combination with teniposide...... was found between cisplatin and carboplatin at the present dosages. Induction chemotherapy with teniposide plus cisplatin or carboplatin did not result in higher complete response rates (objective response rates 63%, 72% and 65%, respectively) or in significantly greater toxicity, but overall survival....... CONCLUSION: Cisplatin and carboplatin produced similar response and survival rates and similar toxicity. Induction with platinum and epipodophyllotoxins did not improve objective response rates, but significantly improved survival without increasing the toxicity....

  18. Theta oscillations accompanying concurrent auditory stream segregation.

    Science.gov (United States)

    Tóth, Brigitta; Kocsis, Zsuzsanna; Urbán, Gábor; Winkler, István

    2016-08-01

    The ability to isolate a single sound source among concurrent sources is crucial for veridical auditory perception. The present study investigated the event-related oscillations evoked by complex tones, which could be perceived as a single sound and tonal complexes with cues promoting the perception of two concurrent sounds by inharmonicity, onset asynchrony, and/or perceived source location difference of the components tones. In separate task conditions, participants performed a visual change detection task (visual control), watched a silent movie (passive listening) or reported for each tone whether they perceived one or two concurrent sounds (active listening). In two time windows, the amplitude of theta oscillation was modulated by the presence vs. absence of the cues: 60-350ms/6-8Hz (early) and 350-450ms/4-8Hz (late). The early response appeared both in the passive and the active listening conditions; it did not closely match the task performance; and it had a fronto-central scalp distribution. The late response was only elicited in the active listening condition; it closely matched the task performance; and it had a centro-parietal scalp distribution. The neural processes reflected by these responses are probably involved in the processing of concurrent sound segregation cues, in sound categorization, and response preparation and monitoring. The current results are compatible with the notion that theta oscillations mediate some of the processes involved in concurrent sound segregation.

  19. [A CASE OF UROTHELIAL CARCINOMA OF THE URINARY BLADDER WITH SQUAMOUS DIFFERENTIATION RESPONDING TO PACLITAXEL AND CARBOPLATIN NEOADJUVANT CHEMOTHERAPY].

    Science.gov (United States)

    Banno, Eri; Nishino, Aki; Nagai, Yasuharu; Yasuda, Muneo; Tahara, Hideo; Kino, Shigeo; Kanno, Norihumi

    2015-07-01

    A 42-year-old man was referred to our hospital for macrohematuria. Computer tomography and magnetic resonance imaging revealed right hydronephrosis and a retroperitoneal mass, located next to right side of the bladder. Cystoscopy showed a protruded lesion covered with normal mucosa at the right lateral wall. The patient underwent transurethral resection of the bladder tumor and biopsies of the bladder wall. Histological examination showed squamous cell carcinoma. Neoadjuvant chemotherapy using paclitaxel and carboplatin (TC) was performed. A total cystectomy, right nephroureterectomy and construction of the ileal conduit were performed after one course of systemic chemotherapy. Histological examination showed urothelial carcinoma with squamous cell differentiation. Unexpectedly, a small amount of CIS was detected only in the vicinity of the TUR scar. The patient received 2 cycles of TC chemotherapy as adjuvant chemotherapy. Unfortunately, 11 months later, local recurrence and liver metastasis were detected. He died 17 months after the surgery.

  20. A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours

    DEFF Research Database (Denmark)

    Lassen, U; Molife, L R; Sorensen, Janice Marie;

    2010-01-01

    This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours.......This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours....

  1. The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro

    Directory of Open Access Journals (Sweden)

    Marley Kevin

    2013-01-01

    Full Text Available Abstract Background Osteosarcoma (OS affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6–12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death. Results Taurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 μM taurolidine and less so in cells exposed to 250 μM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine’s effects may depend on the functional status of p53 in canine OS. Conclusion Taurolidine’s cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.

  2. Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma.

    Directory of Open Access Journals (Sweden)

    Annette Pflugfelder

    Full Text Available BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c received CP as first-line treatment, 41 patients (90.2% M1c had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD (49 weeks compared to patients with progressive disease (18 weeks. CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.

  3. Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.

    Directory of Open Access Journals (Sweden)

    Shailender Bhatia

    Full Text Available BACKGROUND: Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP in metastatic uveal melanoma. METHODS: Twenty-five patients with stage IV uveal melanoma who had received 0-1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6 and paclitaxel (225 mg/m(2 administered IV on day 1 plus sorafenib (400 mg PO twice daily, followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR; a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS and overall survival (OS. RESULTS: No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0-14%] and the study was terminated at the first stage. Minor responses (tumor regression less than 30% were seen in eleven of 24 (45% patients. The median PFS was 4 months [95% CI: 1-6 months] and the 6-month PFS was 29% [95% CI: 13%-48%]. The median OS was 11 months [95% CI: 7-14 months]. CONCLUSION: In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients. TRIAL REGISTRATION: ClinicalTrials.govNCT00329641.

  4. Re-challenge chemotherapy with gemcitabine plus carboplatin in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Khurum Khan; Gerard G. Hanna; Lynn Campbell; Paula Scullin; Adnan Hussain; Ruth L. Eakin; Jonathan McAleese

    2013-01-01

    Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-smal celllung cancer (NSCLC), the patients′overal survival remains poor. Re-chal enging with first-line chemotherapy upon relapse is common in the management of smal celllung cancer but is not wel reported for advanced NSCLC. NSCLC relapse has been attributed to acquired drug resistance, but the repopulation of sensitive clones may also play a role, in which case re-chal enge may be appropriate. Here, we report the results of re-chal enge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months. In this retrospective study, the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed. Al the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study. These patients were offered second-line treatment on confirmation of clear radiological disease progression. The overall response rate was 15%and disease control rate was 75%. The median survival time was 10.4 months, with 46%of patients alive at 1 year. These results suggest that re-chal enge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.

  5. An Algorithm to Construct Concurrent Reachability Graph of Petri Nets

    Institute of Scientific and Technical Information of China (English)

    张金泉; 倪丽娜; 蒋昌俊

    2004-01-01

    Reachability graph is a very important tool to analyze the dynamic properties of Petri nets, but the concurrent relation of transitions in Petri nets cannot be represented by reachability graph. Petri net is a concurrent system, while reachability graph is a serial one. However, concurrency is a kind of property which is not only very significant but also difficult to be analyzed and controlled. This paper presents the concepts of concurrent reachable marking and concurrent reachable graph in order to represent and analyze the concurrent system. The algorithm constructing concurrent reachable marking set and concurrent reachability graph is also shown so that we can study the response problems among services in a network computing environment and analyze the throughput of the system. The Dining Philosophers Problem, which is a classic problem of describing the management of concurrent resources, is given as an example to illustrate the significance of concurrent reachability graph.

  6. Concurrent Scheduling of Event-B Models

    CERN Document Server

    Boström, Pontus; Sere, Kaisa; Waldén, Marina; 10.4204/EPTCS.55.11

    2011-01-01

    Event-B is a refinement-based formal method that has been shown to be useful in developing concurrent and distributed programs. Large models can be decomposed into sub-models that can be refined semi-independently and executed in parallel. In this paper, we show how to introduce explicit control flow for the concurrent sub-models in the form of event schedules. We explore how schedules can be designed so that their application results in a correctness-preserving refinement step. For practical application, two patterns for schedule introduction are provided, together with their associated proof obligations. We demonstrate our method by applying it on the dining philosophers problem.

  7. Models for concurrency: towards a classification

    DEFF Research Database (Denmark)

    Sassone, Vladimiro; Nielsen, Mogens; Winskel, Glynn

    1996-01-01

    Models for concurrency can be classified with respect to three relevant parameters: behaviour/ system, interleaving/noninterleaving, linear/branching time. When modelling a process, a choice concerning such parameters corresponds to choosing the level of abstraction of the resulting semantics....... In this paper, we move a step towards a classification of models for concurrency based on the parameters above. Formally, we choose a representative of any of the eight classes of models obtained by varying the three parameters, and we study the formal relationships between them using the language of category...

  8. Towards Interaction Reliability in Concurrent Applications

    Directory of Open Access Journals (Sweden)

    A. Silva

    2012-01-01

    Full Text Available Developing trustworthy concurrent applications is a seemingly never ending quest, which is necessary but difficult. It is necessary because mainstream systems and applications are inherently concurrent and they are pervasive to our daily life activities. It is difficult because such systems are inherently interactive and heterogeneous, so that boundaries can hardly be established for studying subsystems in isolation. Formal methods are a key instrument in resolving ambiguities and design reliable applications in a rigorous way. The authors overview major problems in the application of formal methods and outline how they are tackled by the papers collected in this volume.

  9. Concurrent sourcing and external supplier opportunism

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    When a firm simultaneously makes and buys the same components then the firm uses concurrent sourcing. This paper presents an agency model for explaining how and when concurrent sourcing reduces the likelihood of external supplier opportunism. In the proposed model, the external supplier’s expected...... costs of opportunism are determined as a product of four factors. The four factors are: likelihood of discovering supplier opportunism, buyer’s internalized quantity as reaction to supplier opportunism, asset specificity of external supplier’s investments, and multiplicator effects. Each...

  10. Notes on Timed Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Valencia, Frank D.

    2004-01-01

    and program reactive systems. This note provides a comprehensive introduction to the background for and central notions from the theory of tccp. Furthermore, it surveys recent results on a particular tccp calculus, ntcc, and it provides a classification of the expressive power of various tccp languages.......A constraint is a piece of (partial) information on the values of the variables of a system. Concurrent constraint programming (ccp) is a model of concurrency in which agents (also called processes) interact by telling and asking information (constraints) to and from a shared store (a constraint...

  11. Authentic And Concurrent Evaluation-refining

    DEFF Research Database (Denmark)

    Eriksson, Carina Ihlström; Åkesson, Maria; Kautz, Karlheinz

    2011-01-01

    This paper addresses the need for more detailed accounts for evaluation in design science research literature. By revisiting a design project regarding the future e-newspaper we give detailed descriptions of its authentic and concurrent evaluation approach by illustrating the what, why and how...... as well as decisions on strategic levels. We emphasize a holistic and concurrent approach to evaluation compared to the general design science research thinking and argue that reflecting on how to seek authenticity is important. By authenticity we refer to the notion of how closely an evaluation captures...

  12. Micro-transactions for concurrent data structures

    DEFF Research Database (Denmark)

    Meawad, Fadi; Iyer, Karthik; Schoeberl, Martin;

    2013-01-01

    Transactional memory is a promising technique for enforcing disciplined access to shared data in a multiprocessor system. Transactional memory simplifies the implementation of a variety of concurrent data structures. In this paper, we study the benefits of a modest, real-time aware, hardware...... implementation of transactional memory that we call micro-transactions. In particular, we argue that hardware support for micro-transactions allows us to efficiently implement certain data structures. Those data structures are difficult to realize with the atomic operations provided by stock hardware and provide......, atomic instructions, and micro-transactions. Our results suggest that transactional memory is an interesting alternative to traditional concurrency control mechanisms....

  13. Concurrent Engineering in seafood product development

    DEFF Research Database (Denmark)

    Jonsdottir, Stella; Vesterager, Johan; Børresen, Torger

    1998-01-01

    Concurrent Engineering (CE) can provide an improved approach to product development for extending the lines of seafood products. Information technology support tools based on product models can provide an integrated and simultaneous approach for specifying new recipes. The seafood industry can...... benefit from the CE approach which can support product developers to provide concurrent specifications for raw materials, ingredients, packaging, and production methods. The approach involves the use of product models from which line extensions are more easily generated than by use of customary stepwise...

  14. The concurrent common Lisp development environment

    Science.gov (United States)

    1988-01-01

    A discussion of the Concurrent Common Lisp Development Environment on the iNTEL Personal Super Computer (iPSC) is presented. The advent of AI based engineering design tools has lead to a need for increased performance of computational facilities which support those tools. Gold Hill has approached this problem by directing its efforts to the creation of a concurrent, distributed AI development environment. This discussion focuses on the development tools aspect of the CCLISP environment. The future direction of Gold Hill in the area of distributed AI support environments is also presented.

  15. Compositional Formal Analysis for Concurrent Object-Oriented Languages

    OpenAIRE

    Tran, Thi Mai Thuong

    2013-01-01

    Concurrency is a ubiquitous phenomenon in modern software ranging from distributed systems communicating over the Internet to communicating processes running on multi-core processors and multi-processors. Therefore modern programming languages offer ways to program concurrency effectively. Still, writing correct concurrent programs is notoriously difficult because of the complexity of possible interactions between concurrent processes and because concurrency-related errors are often subtle an...

  16. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies.

    Science.gov (United States)

    Choy, Hak; Gerber, David E; Bradley, Jeffrey D; Iyengar, Puneeth; Monberg, Matthew; Treat, Joseph; Govindan, Ramaswamy; Koustensis, Andrew; Barker, Scott; Obasaju, Coleman

    2015-03-01

    Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0-16% and 0-23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed-cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.

  17. Survival over ten years after chemotherapy by paclitaxel and carboplatin, followed by a concomitant chemo-radiotherapy in nasopharyngeal undifferentiated carcinomas; Survie a dix ans apres chimiotherapie par paclitaxel et carboplatine, suivie d'une chimioradiotherapie concomitante dans les carcinomes indifferencies du nasopharynx

    Energy Technology Data Exchange (ETDEWEB)

    Djekkoun, R.; Ferdi, N.; Bouzid, K. [CHU de Constantine, Constantine (Algeria)

    2011-10-15

    Based on 28 patients suffering from a cavum carcinoma and having been treated by neo-adjuvant chemotherapy (with paclitaxel and carboplatin) followed by a concomitant chemo-radiotherapy and an adjuvant chemotherapy, the authors analyse the response over time and identify the main causes of death. They also conclude that randomized studies are necessary to better asses the treatment efficiency. Short communication

  18. Concurrent Meta-Evaluation: A Critique

    Science.gov (United States)

    Hanssen, Carl E.; Lawrenz, Frances; Dunet, Diane O.

    2008-01-01

    Meta-evaluations reported in the literature, although rare, often have focused on retrospective assessment of completed evaluations. Conducting a meta-evaluation concurrently with the evaluation modifies this approach. This method provides the opportunity for the meta-evaluators to advise the evaluators and provides the basis for a summative…

  19. CAPP Framework System for Concurrent Engineering

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Difficulty in generalizing and lack of adaptability are important factors that hamper a computer aided process planning (CAPP) system from being popular and practical. New manufacturing philosophies such as Concurrent Engineering require special characteristic of a CAPP system. Proposed in this paper is a CAPP framework system for Concurrent Engineering (CAPPFS-CE) which can meet the requirements of Concurrent Engineering and whose information models, function models and decision logic can be customized by users to form various CAPP application systems. Its function requirements are discussed broadly. An architecture for CAPPFS-CE is presented. It is based on abstract information models (AIMs) and abstract function models (AFMs). The kernel is formed by customization interpretation, internal process control and decision engine. A new information modeling and system development method, information element method (IEM), is introduced to build up AIMs, decision engine, and AFMs and then realize a CAPPFS-CE. THCAPP-SHELL, a CAPPFS-CE developed by IEM, is demonstrated. A CAPP system produced by customizing THCAPP-SHELL for complex structural parts in a concurrent engineering environment is shown.

  20. Logics and Games for True Concurrency

    CERN Document Server

    Gutierrez, Julian

    2010-01-01

    We study the underlying mathematical properties of various partial order models of concurrency based on transition systems, Petri nets, and event structures, and show that the concurrent behaviour of these systems can be captured in a uniform way by two simple and general dualities of local behaviour. Such dualities are used to define new mu-calculi and logic games for the analysis of concurrent systems with partial order semantics. Some results of this work are: the definition of a number of mu-calculi which, in some classes of systems, induce the same identifications as some of the best known bisimulation equivalences for concurrency; and the definition of (infinite) higher-order logic games for bisimulation and model-checking, where the players of the games are given (local) monadic second-order power on the sets of elements they are allowed to play. More specifically, we show that our games are sound and complete, and therefore, determined; moreover, they are decidable in the finite case and underpin nove...

  1. Declarative interpretations of session-based concurrency

    DEFF Research Database (Denmark)

    Cano, Mauricio; Rueda, Camilo; López-Acosta, Hugo-Andrés;

    2015-01-01

    Session-based concurrency is a type-based approach to the analysis of communication-intensive systems. Correct behavior in these systems may be specified in an operational or declarative style: the former defines how interactions are structured; the latter defines governing conditions. In this pa...

  2. Concurrent Engineering Design Using Intelligent Agents.

    Science.gov (United States)

    Parkinson, Brian

    1998-01-01

    Describes Design Builder, interactive multimedia software that was developed to enable undergraduate engineers to experience working in a concurrent environment without direct and specialized teaching-staff support, and to provide an interactive and intelligent simulation environment from which users may develop a culture that introduces…

  3. Concurrent Engineering in the 21st Century

    NARCIS (Netherlands)

    Stjepandic, Josip; Wognum, P.M.; Verhagen, Wim

    2015-01-01

    Presenting the gradual evolution of the concept of Concurrent Engineering (CE), and the technical, social methods and tools that have been developed, including the many theoretical and practical challenges that still exist, this book serves to summarize the achievements and current challenges of CE

  4. Concurrent Engineering Teams. Volume 2: Annotated Bibliography

    Science.gov (United States)

    1990-11-01

    Feigenbaum. A.V., Total Quality Control, McGraw-Hill Book Company, NY, 1983. Goldratt , Eliyahu and Jeff Cox, The Goal, A Process of Ongoing Improvement...design, namely concurrent engineering design for the life cycle. We introduce the emergent notion of Meta -Design, which we believe can be understood

  5. Formal Derivation of Concurrent Garbage Collectors

    NARCIS (Netherlands)

    Pavlovic, Dusko; Pepper, Peter; Smith, Douglas R.

    Concurrent garbage collectors are notoriously difficult to implement correctly. Previous approaches to the issue of producing correct collectors have mainly been based on posit-and-prove verification or on the application of domain-specific templates and transformations. We show how to derive the

  6. Concurrent Validity of a Pragmatic Protocol.

    Science.gov (United States)

    Duncan, Julie Condon; Perozzi, Joseph A.

    1987-01-01

    The scores of 11 non-handicapped kindergarten children on the Pragmatic Protocol (used in assessing language-handicapped children) were correlated with their ratings by five experienced judges on a 7-point equal-appearing interval scale of communicative competence. The concurrent validity of the Protocol and interobserver reliability were…

  7. On run-time exploitation of concurrency

    NARCIS (Netherlands)

    Hölzenspies, Philip Kaj Ferdinand

    2010-01-01

    The `free' speed-up stemming from ever increasing processor speed is over. Performance increase in computer systems can now only be achieved through parallelism. One of the biggest challenges in computer science is how to map applications onto parallel computers. Concurrency, seen as the set of v

  8. Concurrent Engineering Teams. Volume 1: Main Text

    Science.gov (United States)

    1990-11-01

    Delphi Processes. Scott, Foresman, and Co. Glenview, IL. Dertouzos, Michael L.; Lester, Rizhard K.; and Solow , Robert M. 1989. Made in America. Regaining...Nc:%* York. Nevins, James L. and Whitney, Daniel E. 1989. Concurrent Design of F-,oducts and Processes: a Strategy for the Next Generation in

  9. Nonlinear Inequalities and Entropy-Concurrence Plane

    CERN Document Server

    Bovino, F A

    2006-01-01

    Nonlinear inequalities based on the quadratic Renyi entropy for mixed two-qubit states are characterized on the Entropy-Concurrence plane. This class of inequalities is stronger than Clauser-Horne-Shimony-Holt (CHSH) inequalities and, in particular, are violated "in toto" by the set of Type I Maximally-Entangled-Mixture States (MEMS I).

  10. On run-time exploitation of concurrency

    NARCIS (Netherlands)

    Holzenspies, P.K.F.

    2010-01-01

    The `free' speed-up stemming from ever increasing processor speed is over. Performance increase in computer systems can now only be achieved through parallelism. One of the biggest challenges in computer science is how to map applications onto parallel computers. Concurrency, seen as the set of vali

  11. SCOOP Structured Concurrent Object Oriented Prolog

    Science.gov (United States)

    Vaucher, Jean; Lapalme, Guy; Malenfant, Jacques

    SCOOP is an experimental language implemented in Prolog that tries to combine the best of logic, object-oriented and concurrent programming in a structured, natural and efficient manner. SCOOP provides hierarchies of object classes. These objects behave as independent Prolog programs with private databases which can execute goals within other objects.

  12. Verifying Functional Behaviour of Concurrent Programs

    NARCIS (Netherlands)

    Zaharieva, M.; Huisman, Marieke; Blom, Stefan; Pearce, D.

    Specifying the functional behaviour of a concurrent program can often be quite troublesome: it is hard to provide a stable method contract that can not be invalidated by other threads. In this paper we propose a novel modular technique for specifying and verifying behavioural properties in

  13. Integrated concurrent utilization quality review, Part one.

    Science.gov (United States)

    Caterinicchio, R P

    1987-01-01

    This article is the first of a two-part series which argues for the concurrent management of the appropriateness, necessity, and quality of patient care. Intensifying scrutiny by the credentialing groups, the PROs and all third-party payors underscores the vital need to implement cost-effective information systems which integrate the departmentalized functions of patient-physician profiling, DRG case-mix analyses, length of stay monitoring, pre-admission/admission and continued stay review, discharge planning, risk management, incident reporting and quality review. In the domain of physician performance regarding admitting and practice patterns, the ability to exercise concurrent utilization-quality review means early detection and prevention of events which would otherwise result in denials of payment and/or compromised patient care. Concurrent utilization-quality review must, by definition, be managerially invasive and focused; hence, it is integral to maintaining the integrity of the services and product lines offered by the provider. In fact, if PPO status is a marketing agenda, then the institutional objectives of cost-effectiveness, productivity, value, and competitiveness can only be achieved through concurrent utilization-quality review.

  14. Carboplatin dose calculation in lung cancer patients with low serum creatinine concentrations using CKD-EPI and Cockcroft-Gault with different weight descriptors.

    Science.gov (United States)

    Kaag, Dieter

    2013-01-01

    Carboplatin dosing using the Calvert and Cockcroft-Gault formulae in patients with low serum creatinine levels is discussed controversially. We conducted a retrospective analysis applying the CKD-EPI formula and the alternate size descriptors adjusted body weight and predicted normal weight in the Cockcroft-Gault equation for calculating the carboplatin dose. Data were collected retrospectively from 128 lung cancer patients with serum creatinine obese patients they were superior in reducing mean overdose from 24% to roughly 15% (predicted normal weight, CKD-EPI) and 10% (adjusted body weight) and from 25% to 9%, 8% and 4%, respectively. Best performed the combination of Cockcroft-Gault with adjusted body weight. The results show that application of the alternate size descriptor adjusted body weight in the Cockcroft-Gault equation can improve dosing accuracy especially in overweight and obese patients with low serum creatinine levels. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Presurgical window of carboplatin and surgery and multidrug chemotherapy for the treatment of newly diagnosed metastatic or unresectable osteosarcoma: Pediatric Oncology Group Trial.

    Science.gov (United States)

    Ferguson, W S; Harris, M B; Goorin, A M; Gebhardt, M C; Link, M P; Shochat, S J; Siegal, G P; Devidas, M; Grier, H E

    2001-01-01

    Relapse remains a significant problem in patients with metastatic osteosarcoma. The response to carboplatin of patients with newly diagnosed metastatic or unresectable osteosarcoma was assessed in an upfront phase II window, which was followed-up by surgery and intensive multiagent chemotherapy. Thirty-seven patients, ages 3 to 23 years with histologically confirmed diagnoses of osteosarcoma, were treated between January 1992 and November 1994 with carboplatin 1,000 mg/m2 per dose administered as a 48-hour continuous infusion. Two courses were administered in 3-week intervals, depending on marrow recovery. After radiographic reevaluation, patients underwent surgical removal of tumor (if feasible) and then 40 weeks of chemotherapy with high-dose methotrexate, ifosfamide, doxorubicin, and cisplatin. One of the 37 evaluable patients demonstrated a partial response to carboplatin; there were no complete responses. Patients were additionally analyzed by the response of pulmonary metastases to therapy and the extent of tumor necrosis of the primary lesion. By these criteria, 8 of 37 (22%) of patients showed a response at one or more sites, whereas 20 of 37 (54%) had unequivocal disease progression. Severe myelosuppression was the major toxicity. The projected 3-year event-free and overall survival rates were 23.9% and 31.9%, respectively. Only 1 of 17 patients with unresectable disease or distant bone metastases remains alive, in contrast to 6 of 17 patients with the lung as their only metastatic site and two of three patients with resected regional bone metastases. Continuous-infusion carboplatin demonstrated limited activity as an upfront agent in patients with metastatic osteosarcoma at diagnosis, even at doses that result in severe and prolonged myelosuppression. Patients with isolated pulmonary metastases or resectable bone metastases have a longer median survival time and greater chance of long-term survival than do patients with unresectable bone disease, for whom

  16. Phase II Trial of Adjuvant Pelvic Radiation “Sandwiched” Between Combination Paclitaxel and Carboplatin in Women with Uterine Papillary Serous Carcinoma

    Science.gov (United States)

    Einstein, Mark H.; Frimer, Marina; Kuo, Dennis Y-S; Reimers, Laura L.; Mehta, Keyur; Mutyala, Subhakar; Huang, Gloria S.; Hou, June Y.; Goldberg, Gary L.

    2013-01-01

    Objective To evaluate the safety and survival in women treated with adjuvant pelvic radiation “sandwiched” between six cycles of paclitaxel and carboplatin chemotherapy with completely resected UPSC. Methods Surgically staged women with UPSC (FIGO stage 1-4) and no visible residual disease were enrolled. Treatment involved paclitaxel (175 mg/m2) and carboplatin (AUC=6.0-7.5) every 21 days for 3 doses, followed by radiation therapy (RT), followed by an additional 3 cycles of paclitaxel and carboplatin (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least 3 cycles of chemotherapy and RT. Results A total of 81 patients were enrolled, of which 72 patients completed the first 3 cycles of chemotherapy followed by prescribed RT. Median age was 67 years (range: 43–82 years). 59/72 (82%) had disease confined to the uterus and 13/72 (18%) had completely resected extra-uterine disease (stage 3&4). 65 (83%) completed the protocol. Overall PFS and OS for combined stage 1&2 patients was 65.5±3.6 months and 76.5±4.3 months, respectively. PFS and OS for combined stage 3&4 patients was 25.8±3.0 and 35.9±5.3 months, respectively. Three-year % survival probability for stage 1&2 patients was 84% and for stage 3&4 patients was 50%. Of the 435 chemotherapy cycles administered, there were 11(2.5%) G3/G4 non-hematologic toxicities. 26(6.0%) cycles had dose reductions and 37(8.5%) had dose delays. Conclusions Compared to prior studies of single modality adjuvant therapy, RT “sandwiched” between paclitaxel and carboplatin chemotherapy is well-tolerated and highly efficacious in women with completely resected UPSC. PMID:22035806

  17. Outpatient rapid 4-step desensitization for gynecologic oncology patients with mild to low-risk, moderate hypersensitivity reactions to carboplatin/cisplatin.

    Science.gov (United States)

    Li, Quan; Cohn, David; Waller, Allyson; Backes, Floor; Copeland, Larry; Fowler, Jeffrey; Salani, Ritu; O'Malley, David

    2014-10-01

    The primary objective of this study is to assess the efficacy and safety of an outpatient, 4-step, one-solution desensitization protocol in gynecologic oncology patients with history of mild to low-risk, moderate hypersensitivity reactions (HSRs) to platinums (carboplatin and cisplatin). This was a single institutional retrospective review. Gynecologic oncology patients with a documented history of mild or low-risk, moderate immediate HSRs to carboplatin/cisplatin and continued treatment w