tbuckley/cabot-search huggingface dataset:
Abstract 13665: Correlation between Right Arterial Pressure and Right Arterial Volume Index in Patients with Pulmonary Hypertension
Authors: Yuko Fukuda, Hidekazu Tanaka, Yoshiki Motoji, Keiko Ryo, Takuma Sawa, Yasuhide Mochizuki, Junichi Imanishi, Tatsuya Miyoshi, Mana Hiraishi, Akihiro Kaneko, Kazuhiro Tatsumi, Kensuke Matsumoto, Noriaki Emoto, Hiroya Kawai, Ken-ichi Hirata
Journal: Circulation (2012)

Background:  Pulmonary hypertension (PH) is a life-threatening disease and is characterized by a marked and sustained elevation of pulmonary vascular resistance, leading to an increase in pulmonary artery pressure and ultimately death. In addition, right arterial pressure has been reported to be an independent predictor for outcome in PH patients. However, non-invasive assessment of pulmonary arterial pressure is limited and it is commonly estimated by the presence of inferior vena cava dilation and the degree of inspiratory its collapse by echocardiography.   Hypothesis:  Our objective was to test the hypothesis that right atrial volume as assessed by two-dimensional transthoracic echocardiography is correlated to right arterial pressure by hemodynamic measurement in PH patients.   Methods:  A total of 35 PH patients with mean pulmonary artery pressure of 35±10mmHg (all≥25mmHg) were recruited in this study. All patients were underwent echocardiography, and right heart catheterization for the measurement of right atrial pressure. Right atrial volume was assessed by the area-length method in apical 4-chamber view, which focused on the entire right ventricle and atrium, and was corrected for body surface area (right atrial volume index).   Results:  There was a significant correlation between right atrial volume index and right atrial pressure (p   Conclusions:  Non-invasively assessed right arterial volume was associated with right atrial pressure by hemodynamic measurement in PH patients. This approach may have the potential to allow for non-invasive follow-up of PH patients.
Effect of Continuous Positive Airway Pressure on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial
Authors: Elisabet Martínez-Cerón, Beatriz Barquiel, Ana-Maria Bezos, Raquel Casitas, Raúl Galera, Cristina García-Benito, Angel Hernanz, Alberto Alonso-Fernández, Francisco Garcia-Rio
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in patients with diabetes.Objectives: To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants.Methods: In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels equal to or exceeding 6.5% were randomized to CPAP (n = 26) or no CPAP (control; n = 24), while their usual medication for diabetes remained unchanged.Measurements and Main Results: HbA1c levels, Homeostasis Model Assessment and Qualitative Insulin Sensitivity Check Index scores, systemic biomarkers, and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1β, IL-6, and adiponectin also improved in the CPAP group compared with the control group after 6 months. In patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1β were independently related to the 6-month change in HbA1c levels (r2 = 0.510, P = 0.002).Conclusions: Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months resulted in improved glycemic control and insulin resistance compared with results for a control group.Clinical trial registered with www.clinicaltrials.gov (NCT01801150).
A new 5' sequence associated with mouse L1 elements is representative of a major class of L1 termini.
Authors: Véronique Jubier-Maurin, Gérard Cuny, Anne-Marie Laurent, Laurent Paquereau, Gérard Roizes
Journal: Molecular Biology and Evolution (1992)

Full-length L1 elements have been shown to possess, at their 5' end, tandem repeats called "A" or "F" types. By sequencing the 5' region of two large L1 copies that did not hybridize to A or F probes, we have identified a new sequence that is found at the 5' end of many L1 elements and that we call "V." The element characterized has no 200-bp tandem repetitive structure, and the new 5' sequence is not similar to the A or F sequences. The study of the relationships between the V and L1 sequences has shown that only half of the V (i.e., V-specific 5') sequences in the genome are linked to the 5' end of L1 copies. In related rodent species, a comparative study by Southern blot and PCR analysis of the V sequence suggests that this L1 subfamily has an ancient origin and that V sequence isolated from the remainder of the L1 element has been amplified during the evolution of the mouse genome.
Early tumor shrinkage (ETS) and deepness of response (DpR) in patients with metastatic esophageal cancer receiving a first-line treatment with DCF: Exploratory analysis of the JCOG0807.
Authors: Takashi Ura, Shuichi Hironaka, Yasuhiro Tsubosa, Junki Mizusawa, Kozo Kataoka, Ken Kato, Yuko Kitagawa, Takayuki Kii, Akihisa Tomori, Naomi Kiyota, Toshikatsu Taniki, Keisho Chin, Takashi Kojima, Yuichiro Doki
Journal: Journal of Clinical Oncology (2015)

183 Background: ETS and DpR have been recognized as favorable prognostic factors of metastatic colorectal cancer. However, the effect of tumor shrinkage on clinical outcomes has not yet been reported for metastatic esophageal cancer (mEC). The purpose of the present study is to determine the associations of ETS and DpR with progression-free survival (PFS), post-progression survival (PPS), and overall survival (OS) in patients (pts) with mEC. Methods: This exploratory analysis included 53 pts, who received triplet chemotherapy with docetaxel (D) plus CF (cisplatin plus 5-fluorouracil) (DCF) as a first-line treatment during the JCOG0807. ETS after 8 weeks was defined as a relative change of 20% in the sum of the longest diameters of target lesions compared with baseline. DpR was defined as a relative change in the sum of the longest diameters of target lesions at the nadir compared with baseline. The cutoff level of DpR was 30%. PPS was calculated as follows: PPS = OS - PFS. Univariate and multivariate analysis using Cox proportional hazard model was performed to identify a predictor of PFS and OS. Results: Thirty-five of the 53 pts achieved ETS ≥ 20% after 8 weeks. Thirty-seven of the 53 pts achieved DpR ≥ 30%. Pts with ETS ≥ 20% showed longer PFS (7.5 vs. 3.4 months (M), p &lt; 0.001, HR: 0.26, 95% CI 0.14–0.49), longer OS (13.8 vs. 6.1 M, p &lt; 0.001, HR 0.20, 95% CI 0.11–0.39), and longer PPS (6.4 vs. 2.8 M, p = 0.002, HR 0.38, 95% CI 0.20–0.72). Further, pts with DpR ≥ 30% showed longer PFS (7.5 vs. 2.9 M, p &lt; 0.001, HR 0.17, 95% CI 0.08–0.34), longer OS (13.8 vs. 6.0 M, p &lt; 0.001, HR 0.14, 95% CI 0.07–0.27), and longer PPS (6.8 vs. 2.8 M, p &lt; 0.001, HR 0.30, 95% CI 0.15–0.57). Multivariate analysis, including the following additional prognostic variables: age, ECOG PS, the lactate dehydrogenase level, and the number of organs with metastases revealed that ETS ≥ 20% and DpR ≥ 30% were predictors of PFS and OS. Conclusions: ETS and DpR were associated with longer PFS, OS, and PPS. They were also strongly prognostic of PFS and OS in mEC pts treated with DCF. These findings support the treatment strategy involving the highly effective triplet chemotherapy as a first-line treatment of mEC. Clinical trial information: UMIN000001737.
Safety, tolerability and antiviral activity of pradefovir mesylate in patients with chronic hepatitis B virus infection: 48-week analysis of a phase 2 study
Authors: K. S. Lee, S. G. Lim, W. L. Chuang, S. G. Hwang, M. Cho, M. Y. Lai, Y. C. Chao, Ting-Tsung Chang, K. H. Han, C. M. Lee, S. H. Um, J. E. Yeon, S. S. Yang, E. K. Teo, C. Y. Peng, H. H. Lin, T. I. Huo, T. Nguyen, T. Y. Chen, K. Q. Hu, Y. Xu, J. Z. Sullivan-Bólyai
Journal: Journal of Hepatology (2006)
Phase Ib/IIa study of sustained release lipid inhalation targeting cisplatin by inhalation in the treatment of patients with relapsed/progressive osteosarcoma metastatic to the lung
Authors: A. J. Chou, M. D. Bell, C. Mackinson, R. Gupta, P. A. Meyers, R. Gorlick
Journal: Journal of Clinical Oncology (2007)

9525 Background: Pulmonary relapse is the most common site of relapse for patients with osteosarcoma (OS). Few therapeutic options are available for these patients. By encapsulating the drug within liposomes, sustained release lipid inhalation targeting (SLIT) cisplatin is a novel sustained-release formulation of cisplatin designed for administration via inhalation, thereby targeting the lungs with little systemic exposure. Methods: A two-center, open-label, phase Ib/IIa study was designed to characterize the safety and efficacy of SLIT cisplatin in patients with OS metastatic to the lung. Two dose levels were utilized: 24 mg/m 2 /dose, and 36 mg/m 2 /dose. Study drug was administered via nebulizer once every two weeks. OS patients with only pulmonary relapse were eligible. Toxicities were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Response was evaluated radiographically according to the World Health Organization criteria after every 2 cycles. When clinically indicated, metastasectomy was undertaken in patients on study after 2 cycles, and levels of SLIT cisplatin were measured in tumor samples upon metastasectomy. Results: Fourteen patients have been treated on study. SLIT cisplatin has been well tolerated in heavily pre-treated patients who have received multiple cycles of therapy, including one patient, approaching cumulative doses of 840 mg of SLIT cisplatin over one year and a second patient receiving 1,020 mg. Specifically, no patients have experienced hematologic toxicity, nephrotoxicity or peripheral neuropathy. Nausea (= grade 3) was attributed to study drug in 5 patients. Respiratory symptoms (= grade 3) were attributable to study drug in 4 patients. No adverse events required discontinuation of study drug. Two patients are pulmonary disease free one year after initiation of therapy. Conclusions: SLIT cisplatin is well tolerated in patients with pulmonary relapse of OS. Two of 14 patients are pulmonary disease free one year after initiation of therapy. SLIT cisplatin provides a novel therapeutic modality for patients with pulmonary relapse of OS, and warrants further study. No significant financial relationships to disclose.
Impact of IVS14+1G&gt;A and 2846A&gt;T DPYD polymorphisms on toxicity outcome of patients treated with fluoropyrimidine-containing regimens.
Authors: Marzia Del Re, Fotios Loupakis, Cecilia Barbara, Tiziana Latiano, Enrico Vasile, Elena Zafarana, Stefano Sergio Cordio, Luisa Toffolatti, Miriam Ricasoli, Angela Prestifilippo, Filippo Venturini, Samantha Di Donato, Federico Grifalchi, Antonio Rinaldi, Alfredo Butera, Evaristo Maiello, Salvatore Siena, Alfredo Falcone, Federico Cappuzzo, Romano Danesi
Journal: Journal of Clinical Oncology (2013)

11058 Background: DPD deficiency is an inherited syndrome resulting from loss-of-function mutations within the DPYD gene. The IVS14+1G&gt;A variant is associated with DPD deficiency as a result of a 165-bp deletion in the DPD mRNA. A rare mutation, 2846A&gt;T, is characterized by a change of the acidic aspartic acid to the aliphatic valine with potential impairment of enzyme activity (Amstutz et al., 2011). In this study, we describe the spectrum of toxicities of 5-FU and capecitabine in patients carrying the IVS14+1G&gt;A and 2846A&gt;T variants. Methods: Data were collected from 450 patients with gastrointestinal, breast and pancreas cancers. They were evaluated for DPD genotype upon development of grade ≥2 non-hematological and ≥3 hematological toxicities (CTCAE v. 4) secondary to standard fluoropyrimidine-containing regimens in combination with other cytotoxic agents and/or EGFR and VEGF antibodies. DNA was extracted from blood and IVS14+1G&gt;A and 2846T&gt;C DPD variants were screened on a Real-Time Life Sciences 7900 HT platform. The study was approved by the local Ethics Committee. Results: A total of 23 IVS14+1GA, four 2846AT, one IVS14+1AA and one 2846TT subjects were identified. Toxicities in all subjects were G3/4 diarrhea (100%), G3/4 mucositis (48%), febrile neutropenia (45%), G3/4 thrombocytopenia (38%), G3/4 anemia (24%), G2/3 hand-foot syndrome (14%), G3 dermatitis (7%) and G2/4 alopecia (7%). The homozygous IVS14+1AA patient survived because she was given a reduced 5-FU 250 mg/sqm test dose without folates, while the 2846TT patient deceased after the first cycle of FOLFOX4 treatment. Conclusions: Patients carrying the deleterious IVS14+1G&gt;A and 2846T&gt;C variant alleles display severe toxicities which is fatal in homozygous variant subjects. This finding suggests the usefulness of pre-treatment screening of DPD in patients candidates to fluoropyrimidine treatment. Acknowledgmnents. This study was supported by the Italian Association for Cancer Research (AIRC, Milano) and the Istituto Toscano Tumori (ITT, Firenze, Italy). Reference. Amstutz U, Froehlich TK, Largiadèr CR. Pharmacogenomics 2011;12:1321-36.
Interaction between Nrf2 and EGFR signaling in the proliferation of NSCLC cells.
Authors: T. Yamadori, Y. Ishii, S. Honma, M. Kawaguchi, K. Kurishima, Y. Morishima, T. Sakamoto, N. Hizawa
Journal: Journal of Clinical Oncology (2010)

e21062 Background: We previously demonstrated that transcription factor Nrf2 promotes cancer cell proliferation and resistance to anticancer drugs in NSCLC cells. The activation of Nrf2 is regulated negatively by its cytoplasmic inhibitor Keap1 and positively by kinase-mediated phosphorylation. Since Nrf2 and EGFR are abundantly expressed in NSCLC cells, we examined the interaction between Nrf2 activation and EGFR signaling in NSCLC cell lines. Methods: Two human NSCLC cell lines, A549 cells and NCI-H292 cells were treated with EGF. We preliminarily clarified that Nrf2 is constitutively activated in A549 cells because of dysfunctional mutation in the Keap1 gene. NCI-H292 cells possess wild-type Keap1. Cell growth was analyzed by MTT assay. Activation of Nrf2 and the level of phosphorylated EGFR and its downstream signal transducers, p-Akt and p-ERK, were analyzed by immunoblotting. Results: Nrf2 was activated by stimulation with EGFR in NCI-H292 cells. EGFR- mediated activation of Nrf2 was inhibited by EGFR-TKI AG1478 in these cells. Nrf2 was constitutively activated, and the activation was not inhibited by AG1478 in A549 cells. EGFR-mediated activation of Nrf2 was inhibited by a MEK inhibitor U0126, but not by a PI3K inhibitor LY294002 in NCI-H292 cells. EGFR-mediated cell proliferation was significantly inhibited by knockdown of Nrf2 with its specific siRNA. Conclusions: In NCI-H292 cells that possess wild-type Keap1, Nrf2-mediated cell proliferation may be regulated by the EGFR/MAPK signaling pathway. On the other hand, in A549 cells, cell proliferation is not affected by EGFR signaling because of constitutive activation of Nrf2 due to dysfunction of Keap1. Thus, Keap1 gene mutation is a predictable factor for efficacy of EGFR-TKI. No significant financial relationships to disclose.
Treatment Strategy for Conversion Therapy Using Docetaxel/Cddp/S-1 (Dcs) or Dcs-Trastuzumab (Dcs-T) According to Her2 Status in Metastatic Gastric Cancer Patients
Authors: Y. Sato, H. Ohnuma, T. Takayama, T. Sagawa, M. Hirakawa, Y. Sato, Y. Takahashi, M. Takahashi, M. Maeda, S. Katsuki, M. Hirayama, K. Takada, T. Hayashi, T. Sato, K. Miyanishi, M. Kobune, R. Takimoto, T. Nobuoka, K. Hirata, J. Kato
Journal: Annals of Oncology (2014)
Side effects of tacrolimus upon airway epithelial tissue
Authors: Maristela Prado e Silva, Sônia Soto, Francine Almeida, Tatiana Limonete, Edwin Parra, Paulo Pêgo-Fernandes, Fabio Jatene, Rogerio Pazetti
Journal: European Respiratory Journal (2013)

In recent years, tacrolimus has become the most widely used immunosuppressive drug by lung transplant patients. However, tacrolimus is not free of side effects upon cells other than those from immunological system. We hypothesized that tacrolimus could affect airway mucociliary clearance, an important defense mechanism of respiratory tract against infectious agents. Twenty Wistar rats were equally divided into two groups to receive either saline solution (Control) or tacrolimus (TAC, 1 mg/kg/day). After 30 days of therapy by gavage, animals were killed and  in situ  mucociliary transport velocity (MCTV), ciliary beating frequency (CBF) and mucus production were measured. All TAC-treated animals showed a significant decrease in MCTV (1.54±0.42 and 0.79±0.32 mm/min ,  Control and TAC, respectively; p ,  Control and TAC, respectively; p>0.05). These data show that TAC plays an important role on the impairment of the mucociliary clearance which can be related with the high level of respiratory infections observed between 1 and 12 month after lung transplantation. This study was support by Sao Paulo Research Foundation-Fapesp.
A phase II trial of preoperative paclitaxel/ carboplatin with celecoxib followed by adjuvant celecoxib for esophageal cancer: Preliminary report
Authors: N. K. Altorki, J. L. Port, R. J. Korst, R. S. Keresztes
Journal: Journal of Clinical Oncology (2005)

4205 Paclitaxel/carboplatin is an active doublet in patients with esophageal cancer (EC). Preclinically COX-2 inhibition delays tumor growth, decreases angiogenesis and induces apoptosis, thus potentiating the effect of chemotherapy. We conducted a phase II trial of preoperative paclitaxel/carboplatin and celecoxib followed by adjuvant celecoxib in patients with EC. Methods: 28 patients (25 males, 21 adenocarcinoma) were enrolled in this ongoing phase II trial. Eligible patients included stage II, III, and IVA. Patients received two 3 weekly cycles of preoperative paclitaxel (200 mg/m2) and carboplatin (AUC = 6). Preoperative celecoxib (800mg/day) was begun 5 days prior to the first cycle and continued daily to the day of surgical resection. Adjuvant celecoxib (800mg/day) was begun no later than 8 weeks postoperatively. Results: Clinical stages were: stage II: 7, stage III: 16, stage IVA: 5. All patients completed their prescribed cycles of chemotherapy without dose modifications. All patients took their preoperative celecoxib without any adverse events. Chemotherapy related toxicities were as expected. The overall response rate was 57% (CR: 5pts, PR: 11pts, SD:12). Esophagectomy was done in 26 patients to date with no postoperative deaths. Complete pathological response was seen in one patient while in 4 patients only microscopic residual disease was present. Postoperative celecoxib was started on 25 patients.Toxicities possibly related to adjuvant celecoxib included grade 2 dyspepsia in 3 patients, grade 2 diarrhea 1 patient, grade 2 depression 1 patient, and grade 3 insomnia 1 patient. Two patients developed DVT within 30 days of surgery. A third patient with atrial fibrillation and no anticoagulation developed a CVA 6 months postoperatively. Conclusions: The addition of celecoxib of 800mg/day to preoperative paclitaxel/carboplatin in EC patients is safe and well tolerated. In the absence of disease progression adjuvant celecoxib is well tolerated in the majority of patients. Further follow-up is necessary to determine the continued safety of adjuvant celecoxib and its impact on disease progression and overall survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Abstract 3129: Molecular and Physiologic Characterization of RV Remodeling and Failure in a Murine Model of Mild, Moderate and Severe Pulmonary Stenosis
Authors: Takashi Urashima, Mingming Zhao, Roger Wagner, Giovanni Fajardo, Sara Farahani, Tom Quertermous, Daniel Bernstein
Journal: Circulation (2007)

RV dysfunction is a long-term complication in patients after repair of congenital heart disease involving RV outflow obstruction. Despite considerable data on the molecular events of LV remodeling,...
Carboplatin plus paclitaxel (CP) versus carboplatin plus stealth liposomal doxorubicin (CLD) in patients with advanced ovarian cancer (AOC): Activity and safety results of the MITO-2 randomized multicenter trial
Authors: S. Pignata, G. Scambia, A. Savarese, R. Sorio, E. Breda, G. Ferrandina, V. Gebbia, P. Musso, C. Gallo, F. Perrone
Journal: Journal of Clinical Oncology (2009)

LBA5508 Background: CP is standard first-line chemotherapy for AOC. MITO-2 (Multicentre Italian Trials in Ovarian Cancer) is an academic randomized phase III study testing whether CLD is more effective than CP. Methods: AOC patients (pts), stage IC-IV, aged≤75, ECOG PS≤2, were randomized to CP (C AUC5 + P 175 mg/m2,d1q21) or to CLD (C AUC5 + LD 30 mg/m2,d1q21), both for 6 cycles. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival, objective response rate (ORR), toxicity and quality of life. To have 80% power in detecting a 0.80 HR in PFS, with 2-sided α error 0.05, 632 events are needed and 820 pts were planned. Activity was evaluated according to RECIST, toxicity according to NCI-CTC. Activity analysis was not blinded and no confirmation of response was required. Results: From January 2003 to November 2007, 820 pts were randomized, 410 to each arm. Median age was 57 yrs (range 21–77). Stage III (60%) and IV (22%) were prevalent. As of March 30, 2009, with a median follow-up of 35 months, 530 events for PFS and 269 deaths have been recorded. Six cycles were received by 86% and 80% of pts, with CP and CLD respectively. With complete data for 97% of pts, 290 pts were eligible for activity analysis (≥1 target lesion). ORR was 59% with CP and 57% with CLD (p=0.70). In 182 pts with non-target lesions only, complete response was 33% with CP and 29% with CLD (p=0.64). In 168 pts with elevated CA-125 only, CA-125 normalization was obtained in 83% with CP and 86% with CLD (p=0.56). Toxicity data are complete for 97% of pts. Statistically significant differences in haematological toxicity (CP vs CLD) were: anemia all grades 59% vs 68%, grade (G) 3–4 4% vs 10%; thrombocytopenia all grades 19% vs 48%, G3–4 2% vs 16%. Statistically significant differences in non haematological toxicity were: hair loss 63% vs 14%; skin toxicity all grades 6% vs 20%, G3–4 0 vs 2%; diarrhea all grades 13% vs 6%; stomatitis all grades 9% vs 20%; neurotoxicity all grades 47% vs 15%, G3–4 3% vs 0.3%. Conclusions: CLD as first-line treatment of AOC produced a similar activity, with a different toxicity profile, compared to CP. Required events are awaited for final PFS analysis. Partially supported by Schering-Plough. No significant financial relationships to disclose.