tbuckley/cabot-search huggingface dataset:
High-dose consolidation therapy with autologous stem-cell rescue in stage IV breast cancer: follow-up report.
Authors: S F Williams, T Gilewski, R Mick, J D Bitran
Journal: Journal of Clinical Oncology (1992)

PURPOSE Fifty-nine patients with newly diagnosed metastatic breast cancer were treated with induction chemotherapy followed by high-dose intensification and autologous stem-cell rescue (ASCR) to determine therapeutic efficacy. PATIENTS AND METHODS Induction consisted of cyclophosphamide, doxorubicin, vincristine, and methotrexate with leucovorin rescue (LOMAC) in 27 patients, or fluorouracil, cisplatin, doxorubicin, and cyclophosphamide (FCAP) in 32 patients. Intensification after LOMAC was cyclophosphamide and thiotepa (CyTepa) with ASCR, and after FCAP it was cyclophosphamide, thiotepa, and carmustine (BCNU) in all but eight patients who received CyTepa. RESULTS Median survival from study entry for the entire group was 13.3 months. Median time to progression from reinfusion for the 45 patients who underwent intensification was 7.5 months. After LOMAC and intensification, there were 12 complete responses (CR) (nine partial responses [PRs] after induction converted to CRs). Responses after FCAP and intensification were eight CRs (two PRs after induction converted to CRs). Median time to treatment failure from reinfusion was 5.4 months for LOMAC and intensification, and was 10.5 months for FCAP and intensification. Median survival from study entry was 15.1 months for all 27 LOMAC patients and 9.3 months for all 32 FCAP patients. Median time to treatment failure from reinfusion for 11 patients who were CRs at intensification has not been reached and is more than 13 months compared with a median of 5.5 months for the 23 patients in partial remission at intensification. CONCLUSIONS High-dose intensification therapy has led to increased CR rates in metastatic breast cancer. The role of such therapy in the treatment of stage IV breast cancer requires further refinement.
Therapeutic efficacy of a novel FAK inhibitor TAE226 in ovarian carcinoma
Authors: Jyotsnabaran Halder, Yvonne Lin, William Merritt, Aparna Kamat, Liz Han, Tae-Jin Kim, Chunhua Lu, Robert Coleman, Anil Sood
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3751 

Objective: Focal adhesion kinase (FAK) overexpression is frequently found in ovarian and other cancers and is predictive of poor clinical outcome. In the current study, we characterized the biological and therapeutic effects of a novel FAK inhibitor,TAE226.

Methods: Taxane-sensitive (SKOV3ip1 and HeyA8) and taxane-resistant (HeyA8-MDR) cell lines were used for in vitro and in vivo therapy experiments using TAE226 alone and in combination with docetaxel. Assessment of cell proliferation (PCNA), angiogenesis (CD31 staining) and apoptosis (TUNEL) was performed by immunohistochemical and immunofluorescence techniques.

Results: In vitro , TAE226 inhibited phosphorylation of FAK at both Y397 and Y861, inhibited cell growth in a time- and dose- dependent manner, and enhanced docetaxel-mediated growth inhibition by 10 and 20 fold in the taxane-sensitive and resistant cell lines, respectively. In vivo , FAK inhibition by TAE226, significantly reduced tumor burden in the HeyA8, SKOV3ip1, and HeyA8-MDR models compared to the vehicle treated controls. Treatment with both TAE226 and docetaxel had greater efficacy than either agent alone in all three models (HeyA8: 75% reduction; p<0.002; SKOV3ip1: 97% reduction; p<0.001; HeyA8-MDR: 70% reduction; p<0.04). In addition, TAE226 alone and in combination with chemotherapy prolonged survival in tumor-bearing mice. Even in larger tumors, combination therapy with TAE226 and docetaxel resulted in tumor regression, as determined by bioluminescent imaging. Combination therapy induced apoptosis of tumor-associated endothelial cells and reduced microvessel density and tumor cell proliferation compared to control and single-agent therapy.

Conclusions: TAE226 in combination with docetaxel is highly effective for the treatment of ovarian carcinoma. Therefore, FAK inactivation may be an attractive therapeutic approach against ovarian cancer.
A Pooled Analysis of Four Pivotal Studies of Rivaroxaban for the Prevention of Venous Thromboembolism after Orthopaedic Surgery: Effect on Symptomatic Venous Thromboembolism, Death, and Bleeding
Authors: Alexander GG Turpie, Michael Rud Lassen, Ajay K Kakkar, Bengt Eriksson, Frank Misselwitz, Tiemo Joerg Bandel, Martin Homering, Torsten Westermeier, Michael Gent
Journal: Blood (2008)
Abstract 10758: Prognostic Importance of Late Gadolinium Enhancement Cardiac Magnetic Resonance as a Potential Novel Risk Factor in Patients with Dilated Cardiomyopathy
Authors: Emi Tateishi, Teruo Noguchi, Yoshiaki Morita, Naoaki Yamada, Toshihisa Anzai, Masaharu Ishihara, Wataru Shimizu, Yoichi Goto, Hisao Ogawa, Satoshi Yasuda
Journal: Circulation (2012)

Background: Cardiac magnetic resonance (CMR) has revolutionized providing information regarding cardiac anatomy and function, particularly through the use of late gadolinium enhancement (LGE) imagi...
Surgery of the recurrent dysphagia after prior operations for cardiospasm
Authors: Georgy Pahomov, Otabek Eshonhodjaev, Rustem Hayaliev, Antony Malkov
Journal: European Respiratory Journal (2013)

Introduction: The problem of surgical treatment of cardiospasm still represents a complicated challenge. It is even more complicated by the fact that a number of surgeons keep using an operative method as fundamental without even making cardiodilatation attempts. Materials and methods: 32 patients with relapse of dysphagia after previous operations for cardiospasm aging from 28 to 75 were treated in the department of oesophagus and stomach surgery. There were 12 men and 20 women. A strong cicatrical stricture of cardioesophageal transition and the lower third of thoracic section of oesophagus has been diagnosed in 3 patients. Different stages of cardiospasm has been diagnosed in 29 patients, of which in 9 patients – II stage, in 15 patients – III stage and in 5 patients – IV stage.

Results and discussions: The following variants of treatment have been performed by us:

1. Conservative treatment has been performed in 5 patients.

2. Bougienage of the esophagus has been performed in 4 patients. It was only possible treatment method in patients of this category.

3. Cardiodilatation has been performed in 18 patients: pneumatic one in 17 patients and the one with Shtark apparatus in 1 patient. In 3 patients cardiodilatation was complicated by erosive esophagitis, which has been liquidated by conservative measures. There haven’t been other complications. Results were as follows: good –in 7 patients, satisfactory– in 10 patients and unsatisfactory in 1 patient.

4. Surgical treatment has been performed in 5 patients. Indications for surgery treatment were ineffectiveness of bougienage or cardiodilatation and also the impossibility of conducting the bougie or dilator through cicatrically narrowed cardia.
Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies
Authors: Nathan Singh, Jessica Perazzelli, Stephan A. Grupp, David M. Barrett
Journal: Science Translational Medicine (2016)

Engineered T cell therapies have begun to demonstrate impressive clinical responses in patients with B cell malignancies. Despite this efficacy, many patients are unable to receive T cell therapy because of failure of in vitro expansion, a necessary component of cell manufacture and a predictor of in vivo activity. To evaluate the biology underlying these functional differences, we investigated T cell expansion potential and memory phenotype during chemotherapy in pediatric patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). We found that patients with T cell populations enriched for early lineage cells expanded better in vitro and that patients with ALL had higher numbers of these cells with a corresponding enhancement in expansion as compared to cells from patients with NHL. We further demonstrated that early lineage cells were selectively depleted by cyclophosphamide and cytarabine chemotherapy and that culture with interleukin-7 (IL-7) and IL-15 enriched select early lineage cells and rescued T cell expansion capability. Thus, early lineage cells are essential to T cell fitness for expansion, and enrichment of this population either by timing of T cell collection or culture method can increase the number of patients eligible to receive highly active engineered cellular therapies.
Epidermal Electronics: Cephalopod‐Inspired Miniaturized Suction Cups for Smart Medical Skin (Adv. Healthcare Mater. 1/2016)
Authors: Moon Kee Choi, Ok Kyu Park, Changsoon Choi, Shutao Qiao, Roozbeh Ghaffari, Jaemin Kim, Dong Jun Lee, Myungbin Kim, Wonji Hyun, Seok Joo Kim, Hye Jin Hwang, Seung‐Hae Kwon, Taeghwan Hyeon, Nanshu Lu, Dae‐Hyeong Kim
Journal: Advanced Healthcare Materials (2016)

On page 80, D.-H. Kim and co-workers exploit bio-inspired designs and geometries to create cephalopod-inspired dry adhesives in combination with ultrathin stretchable electronics. The ultra-low modulus (∼108 kPa) miniaturized suction cups support stretchable electronics and drug-loaded therapeutic nanoparticles, enabling tight skin coupling without irritations. The integrated system allows continuous vital sign monitoring, controllable drug release, and wireless communication to external devices for remote data transmission and drug delivery actuation.
Positron emission tomography using 18-fluorodeoxyglucose in pre- and post-transplantation in lymphoma patients treated with autologous stem cell transplantation: Impact
Authors: X. Cuenca, N. Mounier, G. L. Deville, P. Brice, J. Larghero, A. Haddad, M. Ertault, J. Filmont, J. Moretti, J. Briere, E. De Kerviler, C. Hennequin, C. Gisselbrecht
Journal: Journal of Clinical Oncology (2007)

8060 Background: The pre-transplant evaluation of lymphoma with Positron Emission Tomography (PET) scanning using 18- FluoroDeoxyGlucose may ease a decision making. The impact on patient outcome of post-transplant assessment is unknown. Methods: Between July 04 and December 05, patients (pts) who achieved tumor response and received high-dose chemotherapy plus autologous stem cell transplantation (ASCT) were explored with PET, prior and 100 days after ASCT, without knowledge of conventional imaging nor clinical history. PET results (negative or positive) were related to event-free survival (EFS) and overall survival (OS). Results: 60 pts were included. 50 had Non-Hodgkin Lymphoma (26 aggressive) and 10 Hodgkins Lymphoma. Median age was 52 [19-68]. 22 pts received front-line ASCT mainly after ACVBP (n=14) or CHOP. Platinum-based salvage chemotherapy was the most used (n=38), and most of the pts received rituximab (n=40). Prior ASCT,by clinical staging, there were 31 complete remission (CR), 23 uncertain CR and 6 partial remission. Conditioning regimen was BEAM in 39 pts; Zevalin BEAM in 11, Total Body Irradiation in 10. 75% were pre-ASCT-PET negative and 80% post-ASCT-PET negative. 6 pts (10%) converted from pre-ASCT-PET positive to post-ASCT-PET negative and 2 pts from negative to post-ASCT-PET positive. Median follow-up was 1.25 years [0.5–2]. 12 pts died (OS 80%) and 19 relapsed (EFS 68%). OS and EFS was better in pre-ASCT-PET-negative pts than in PET-positive (92% vs 53% (p=0.0009), 77% vs 35%, (p=0.0002) respectively). OS was estimated to 90% in post-ASCT-PET-negative pts vs 50% in PET-positive (p&lt;0.0001), EFS was 79% vs 25%, respectively (p&lt;0.0001). In multivariate analysis,including analysis by histology subtypes, the only adverse prognostic factor was PET positive either pre-ASCT (Relative Risk(RR)=4) or post-ASCT (RR=12). Conclusions: A positive PET after induction chemotherapy indicates a high risk of ASCT failure which is increased by a positive PET after ASCT. In pre-ASCT-PET-positive pts, more experimental approaches are required. In pre-ASCT-PET-negative patients, post-ASCT-PET assessment may be omitted. No significant financial relationships to disclose.
Survival of patients with soft tissue sarcoma (STS) correlated to tumor grade, size, site of origin & cell type. Does the high risk group need adjuvant systemic therapy?
Authors: E. G. Elias, S. D. Brown, O. K. Dorsi, C. J. You, A. M. Nitz
Journal: Journal of Clinical Oncology (2006)

19510 Background: The prognosis of patients with STS depends on the tumor stage, which includes tumor size (T) and grade (G). Patients with low-grade tumors (G1) are managed by radical resection only. Patients with moderate (G2) and high-grade (G3) tumors require postoperative adjuvant radiation therapy (RT); this became standard therapy. This study was conducted to determine the efficacy of standard therapy on survival. Methods: This is a retrospective study of patients with primary STS, excluding those with skin, subcutaneous tissue and GIST. All patients underwent radical resections (S). Postoperative RT was requested for G2 and G3 tumors; 6 patients with G3 tumors received chemotherapy (C) prior to RT. Results: 52 patients were studied with a median follow-up of 84 mo. The overall survival ranged from 3 to 264 mo. with a median of 52 mo. The incidence of tumor grade and size were correlated to the survival. 37 patients had STS of the extremities and torso; 24 are alive. 10 patients had intra- and retro-peritoneal STS; 5 are alive. 4 of the 6 patients who received C are alive, 3 are disease-free for a period of 3 to 7 years. Life table analysis of patients with G3T2 tumors comparing the 3 treatment groups (S vs. S+RT vs. S+C+RT) showed no statistical difference in survival, but there was a trend in favor of S+C+RT. Conclusions: 1. Radical resection and postoperative RT may be insufficient for systemic control. 2. Adjuvant systemic chemotherapy may improve the survival, and may be safer than RT in the management of retroperitoneal and visceral sarcomas. [Table: see text] No significant financial relationships to disclose.
Randomized phase II study of clofarabine versus clofarabine plus low-dose cytarabine (ara-C) for patients (pts) ≥ 60 years (yrs) with newly diagnosed acute myeloid leukemia (AML)
Authors: S. Faderl, F. Ravandi-Kashani, A. Ferrajoli, Z. Estrov, W. Wierda, S. Verstovsek, G. Garcia-Manero, E. E. Estey, M. Kwari, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2005)

6627 Background: Outcome of pts ≥ 60 yrs with AML remains poor. Although response rates with standard chemotherapy may exceed 50%, toxicity is substantial, relapse rates are high, and long-term DFS is rare. Clofarabine is a next-generation nucleoside analog with activity in AML. In a recent trial of clofarabine + intermediate dose ara-C for pts ≥ 50 yrs with newly diagnosed AML, we have reported a 60% OR (51% CR) rate with a low induction mortality of 7% (Blood 2004; 104: abs #875). Here we report preliminary results of a lower dose schedule of clofarabine +/- low-dose ara-C (LDAC) in pts ≥ 60 yrs with AML. Methods: Pts with untreated AML are randomized to induction therapy with either clofarabine alone (clofarabine 30mg/m2/d i.v. d1–5) or clofarabine plus LDAC (clofarabine 30mg/m2/d i.v. d1–5 + ara-C 20mg/m2/d s.c. d1–14). Pts in remission receive consolidation therapy q4–7 wks with clofarabine administered on d1–3 and LDAC on d1–7 per course, respectively. Pts are excluded for ECOG PS > 2 and a history of NYHA grade 3 heart disease. Randomization of pts will be adaptive after the first 20 pts have been randomized with equal probability to either arm and have been evaluated for response. Primary endpoints include evaluation of efficacy (CR rate, CR duration) and tolerability. Results: Fourteen pts have been enrolled (7 in each arm) of whom 10 are evaluable for response. Median age: 72 yrs (range 60–83). Five pts (50%) had secondary AML with an antecedent hematologic disorder (AHD) and 5 pts (50%) had abnormal cytogenetics. Seven pts (70%) achieved CR after one course (4 of 5 on clofarabine and 3 of 5 on clofarabine + LDAC). Median time to CR: 33 days (25–47). Four CR pts (57%) had abnormal cytogenetics and 3 (43%) had AHD. Two pts (20%) experienced early death, which was not considered related to study drugs: 71 yo female with E. coli sepsis on d12 (clofarabine); 83 yo male with pulmonary hemorrhage and pneumonia d14 (clofarabine + LDAC). Conclusions: Both clofarabine and clofarabine + LDAC are active in older pts with AML. Although the toxicity profile is favorable, myelosuppression is common. An update of responses and toxicity profile will be presented. No significant financial relationships to disclose.
Phase I/II study of induction weekly paclitaxel, ifosfamide and carboplatin (PIC) followed by chemoradiotherapy (CRT) in advanced head and neck squamous cell cancers (HN-SCC)
Authors: R. Rathore, P. Chougule, H. Wanebo, A. Nadeem, K. Radie-Keane, W. Sikov, P. Negri, T. Kennedy, N. Ready
Journal: Journal of Clinical Oncology (2004)

5602 Background: CRT for Stage III/IVA HN-SCC improves local control and survival. Multiple reports show higher rates of systemic than local failures. We are performing this outpatient phase I/II study to determine the optimal dose and efficacy of induction weekly PIC chemotherapy in these patients (pts). Methods: Pts were stratified as operable versus inoperable. In the phase I portion, escalating doses of Paclitaxel (P) 60, 80 or 100 mg/m2 with Ifosfamide (I) 1000mg/m2 and Carboplatin (C) AUC=2 were given weekly for 6 of 8 weeks. Mesna 1000 mg/m2 was co-administered with I. CRT consisted of weekly P 40mg/m2 and C AUC=1 with RT 1.8 Gy/day (total 66–72 Gy). Inoperable pts received 8 weeks CRT while operable pts underwent primary site biopsy after 5 weeks. Biopsy positive pts underwent surgery and post op RT. Biopsy negative pts received 3 more weeks of CRT. Results: Of 15 pts enrolled, 1 refused therapy, 1 had lung metastases, and 1 had major dosing error. The rest (M= 9, F= 3) had a median age of 55 yrs (range 30–78). PS was 0 (n=10) or 1 (n=2). TNM stages were III (n= 5) or IV (n= 7). Dose levels 1 and 3 were well tolerated. Level 2 was expanded due to 1 pt receiving < 80% planned dose. Major toxicities are tabulated below. Phase I responses after completing PIC and CRT were: primary site path CR in 11 pts (92%) & SD in 1 pt (8%); residual nodal disease in 1 pt (8%) at neck dissection. Using the level 3 dose as the phase II dose, an additional 18 pts have finished PIC. Conclusions: Outpatient weekly dose intense induction chemotherapy with PIC is well tolerated with a favorable toxicity profile. Patient accrual is continuing at the phase II dose of P 100 mg/m2, I 1000mg/m2 and C AUC=2 given weekly for 6 of 8 weeks. Initial efficacy results will be available at the time of presentation. No significant financial relationships to disclose.
Abstract 17726: Comprehensive Evaluation of QT Interval During Abrupt Changes in Heart Rate and Associated Neurohormonal and Inflammatory Markers
Authors: Matthew J Kolek, Babar Parvez, Yanna Song, Robert L Abraham, Dan M Roden, Dawood Darbar
Journal: Circulation (2014)

Background: QT interval prolongation and risk of torsades de pointes have been associated with abrupt heart rate (HR) slowing after cardioversion from atrial fibrillation (AF) or AV nodal ablation. The degree to which the QT interval prolongs with abrupt changes in HR, and the underlying mechanisms, are poorly understood. We quantified ΔQT interval during cessation of rapid pacing and examined the relationship between QT and circulating neurohormonal and inflammatory markers. Methods: Eleven subjects with dual chamber pacemakers and intact AV conduction were atrially-paced at 90/min for 10 min, 60 min, and 1 week (Figure). Biomarkers were sampled during and after pacing. The relationships between QT, pacing stage, and biomarker levels were analyzed with a mixed effect model. QT intervals were compared for the 20 RR intervals before and 100 RR intervals after each pacing stage. Results: QT intervals prolonged after cessation of rapid pacing: 6.4 ms (95% confidence interval 4.9-7.8 ms) after 10 min (P&lt;0.0001), 6.1ms (4.6-7.5 ms) after 60 min (P&lt;0.0001), and 2.2ms (0.9-3.6 ms) after 1 week (P=0.002). QT interval was significantly associated with angiotensin II (P=0.002), epinephrine (P&lt;0.0001), norepinephrine (P=0.03), dopamine (P&lt;0.0001), C-reactive protein (P=0.0005), and interleukin-6 (P&lt;0.0001), but not associated with atrial natriuretic peptide (P=0.26), B-type natriuretic peptide (P=0.08), renin (P=0.25), or aldosterone (P=0.42). There were no significant inter-individual differences in biomarker levels drawn before and after pacing (P&gt;0.1 for all comparisons). Conclusion: Abrupt decreases in HR were associated with QT prolongation. QT interval changes correlated with several neuroendocrine and inflammatory biomarkers, though there were no inter-individual differences in biomarker levels before and after pacing. These findings may partially explain the increased risk of torsade de points after restoration of sinus rhythm from AF.
Role of Human Papillomavirus in Penile Carcinomas Worldwide
Authors: Laia Alemany, Antonio Cubilla, Gordana Halec, Elena Kasamatsu, Beatriz Quirós, Emili Masferrer, Sara Tous, Belén Lloveras, Gustavo Hernández-Suarez, Ray Lonsdale, Leopoldo Tinoco, Maria Alejo, Isabel Alvarado-Cabrero, Jan Laco, Nuria Guimerà, Enrique Poblet, Luis E. Lombardi, Christine Bergeron, Omar Clavero, Hai-Rim Shin, Annabelle Ferrera, Ana Felix, Julieta Germar, Vaclav Mandys, Christine Clavel, Maria Tzardi, Luis E. Pons, Vincent Wain, Eugenia Cruz, Carla Molina, Jose D. Mota, Robert Jach, Julio Velasco, Carla Carrilho, Ruben López-Revilla, Marc T. Goodman, Wim G. Quint, Xavier Castellsagué, Ignacio Bravo, Michael Pawlita, Nubia Muñoz, F. Xavier Bosch, Silvia de Sanjosé
Journal: European Urology (2016)
Sequence Effect of Epirubicin and Paclitaxel Treatment on Pharmacokinetics and Toxicity
Authors: Marco Venturini, Gianluigi Lunardi, Lucia Del Mastro, Maria Ornella Vannozzi, Giuseppina Tolino, Gianmauro Numico, Maurizio Viale, Ilaria Pastrone, Catia Angiolini, Gianfilippo Bertelli, Manuela Straneo, Riccardo Rosso, Mauro Esposito
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Sequence-dependent clinical and pharmacokinetic interactions between paclitaxel and doxorubicin have been reported. Some data have shown an influence of paclitaxel on epirubicin metabolism, but no data are available about the effect of diverse sequences of these drugs. We investigated whether reversing the sequence of epirubicin and paclitaxel affects the pattern or degree of toxicity and pharmacokinetics. PATIENTS AND METHODS: Patients receiving epirubicin 90 mg/m 2 by intravenous bolus followed by paclitaxel 175 mg/m 2 over 3-hour infusion or the opposite sequence every 3 weeks for four cycles were eligible. Toxicity was recorded at nadir. Pharmacokinetic data were evaluated at the first and the second cycle and were correlated with toxicity parameters. RESULTS: Thirty-nine consecutive stage II breast cancer patients were treated. Twenty-one patients received epirubicin followed by paclitaxel (ET group), and 18 received the opposite sequence (TE group). No significant difference in nonhematologic toxicity was seen. A lower neutrophil and platelet nadir and a statistically significant slower neutrophil recovery was observed in the TE group. Area under the concentration-time curve (AUC) of epirubicin was higher in the TE group (2,346 ng/mL · h v 1,717 ng/mL · h; P = .002). An inverse linear correlation between epirubicin AUC and neutrophil recovery was also observed (P = .012). No difference was detected in paclitaxel pharmacokinetics. CONCLUSION: Our results support a sequence-dependent effect of paclitaxel over epirubicin pharmacokinetics that is associated with increased myelotoxicity. Because schedule modifications of anthracyclines and paclitaxel can have clinical consequences, the classical way of administration (ie, anthracyclines followed by paclitaxel) should be maintained in clinical practice.