tbuckley/cabot-search huggingface dataset:
DECREASED AORTIC INERTANCE IS INDEPENDENTLY ASSOCIATED WITH LEFT VENTRICULAR HYPERTROPHY: ROLE IN VENTRICULAR-ARTERIAL COUPLING
Authors: Timothy S. Phan, Zeba Hashmath, Amer Ahmed Syed, Izzah Vasim, Uzma Kewan, Swapna Varakantam, Scott R. Akers, Julio A. Chirinos
Journal: Journal of the American College of Cardiology (2017)
Long-term cure after complete resection and adjuvant immunotherapy for distant melanoma metastases.
Authors: Donald L. Morton, Nicola Mozzillo, Mohammed Kashani-Sabet, John F Thompson, Mark C. Kelley, Ronald C. De Conti, Jeffrey Edwin Lee, James F. Huth, Mark B. Faries, Angus George Dalgleish, Jeffrey D. Wagner, Evan Hersh, Schlomo Schneebaum, Clay M. Anderson, Mark Smithers, Lynn Mara Schuchter, Kelly M. McMasters, Alessandro Testori, C. P. Karakousis, Robert Elashoff
Journal: Journal of Clinical Oncology (2012)

8534 Background: In phase II trials, postoperative therapy with Canvaxin allogeneic melanoma cell vaccine plus Bacillus Calmette-Guerin (BCG) improved the survival of patients with stage IV melanoma. A multicenter, phase III placebo-controlled study was undertaken to investigate the vaccine’s efficacy. Methods: After complete resection of melanoma involving up to 5 distant sites, patients were randomized to treatment with BCG plus Canvaxin (BCG-Canvaxin) or BCG plus placebo (BCG-placebo). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS) and skin test responsiveness to the study agent. Results: Between May 1998 and April 2005, 496 patients were randomized. In April 2005, entry to the study was terminated due to low probability of demonstrating treatment differences. However, 256 patients from sites enrolled in a follow-up study were monitored until March 2010. Median OS and 5-year and 10-year rates of OS were 39.1 months, 43.3% and 33.3%, respectively, in the BCG-placebo group, versus 34.9 months, 42.5% and 36.4%, respectively, in the BCG-Canvaxin group (hazard ratio, 1.053; 95% confidence interval, 0.81 to 1.36; p=0.6964). Median DFS, 5-year DFS, and 10-year DFS were 7.6 months, 23.8% and 21.7%, respectively, for the BCG-placebo group, versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG-Canvaxin group (hazard ratio, 0.882; 95% confidence interval, 0.708 to 1.097; p=0.2595). Positive skin test results correlated with improved survival. Conclusions: BCG-Canvaxin was not superior to BCG-placebo, but the highly favorable long-term survival for combined groups indicates that complete metastasectomy should be considered as initial therapy for patients with resectable stage IV melanoma (ClinicalTrials.gov identifier: NCT00052156).
A phase I study of neoadjuvant chemotherapy (NCT) with the gamma secretase (GS) inhibitor RO4929097 in combination with paclitaxel (P) and carboplatin (C) in women with triple-negative breast cancer (TNBC).
Authors: Ewa Mrozek, Robert Wesolowski, Maryam B. Lustberg, Rachel M. Layman, Yonghua Ling, Larry J. Schaaf, Mitch A. Phelps, S. Percy Ivy, Michael R. Grever, Charles L. Shapiro
Journal: Journal of Clinical Oncology (2013)

1043 Background: Notch receptors are overexpressed in TNBC. Notch activation involves the cleavage of Notch ligand/receptor complex by GS. RO4929097 (RO) is an oral inhibitor of GS. We are conducting a phase I NCT trial of intermittent RO in combination with P and C in TNBC to determine the dose limiting toxicity (DLT) and the maximum-tolerated dose (MTD) of RO. Because RO induces CYP3A4/5, plasma P and RO are quantified in real time to ensure P AUC exposure is not decreased. Methods: Women ≥ 18 years with clinical stage II/III TNBC received C AUC=6 on day 1 and weekly P 80 mg/m2 in combination with RO on days 1-3, 8-10 and 15-17 for six 21-day cycles. The starting dose of RO was 10 mg and escalated according to the 3+3 rule. DLT was defined as grade ≥3 (G3) non-hematologic toxicity (n-HT), grade 4 (G4) thrombocytopenia (TCP) or G4 neutropenia (NP) during cycle#1 (c1). Plasma specimens were analyzed for PK by a validated LC-MS/MS assay. Results: 13 pts were enrolled. Two pts enrolled at 10 mg RO with C AUC 6 developed G3,4 TCP during c1. The study was amended; the dose of C was decreased to AUC 5. No DLTs were observed with 10 mg RO and C AUC 5. Only 1 DLT ( G3 HTN) occured with 20 mg RO, but all 4 pts enrolled on this cohort required dose reductions of RO during subsequent cycles. The RO dose was de-escalated to 10 mg, additional 3 pts were treated with 10 mg RO. G≥3 HT included: G4 NP in 2 pts, G4 TCP in 1 pt, G3 NP in 6 pts, G3 anemia in 4 pts and G3 TCP in 5 pts. G≥3 n-HT included: G3 sensory neuropathy in 3 pts. G3 HTN, G3 fatigue and G3 depression occured in 1 pt each. There were no hospitalizations for treatment-related toxicities. PK studies indicate that P AUC ranged from 80% to 134% on week 3 compared to week 1. Ten pts completed 6 cycles of NCT, 3 are still receiving NCT. Five of 10 (50%) pts had complete pathologic response (pCR) in breast and axilla and 3 (30%) pts had minimal residual cancer in breast. Conclusions: The MTD of intermittent RO administered in combination with P and C is 10 mg. This MTD does not result in decreased P exposures. The pCR (50%) and minimal residual disease (30%) suggests this regimen is active in TNBC. Supported by the NCI/NIH Award Number U01CA076576. Clinical trial information: NCT01238133.
Computerized Clinical Decision Support Systems for Prevention of Venous Thromboembolism
Authors: Brandyn D. Lau, Elliott R. Haut
Journal: JAMA Surgery (2017)

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The vitamin D receptor: A therapeutic target for the treatment of breast cancer?
Authors: Alyson M Murray, Naoise C Synnott, John Crown, Norma O'Donovan, Michael J. Duffy
Journal: Journal of Clinical Oncology (2015)

534 Background: Recent studies suggest vitamin D (VD) plays a role in cancer cell growth, with evidence indicating that a deficiency can lead to higher disease risk and a poorer outcome. Activation of the vitamin D receptor (VDR) by the active form of VD (calcitriol) leads to the regulation of anti-cancer genes. Therefore, we propose that VDR could be targeted as a potential therapeutic for treatment of breast cancer. Methods: The effects of calcitriol and inecalcitol (Hybrigenics, Paris) on breast cancer (BC) cell growth were investigated in 16 cell lines (TN = 7, Her2+ = 5, luminal = 4) and 7 cell lines (TN = 3, Her2+ = 2, luminal = 2), respectively. Cytotoxicity was determined by MTT assays and cell proliferation by colony formation assays (CFA). VDR expression was measured by ELISA (USCN Life Science Inc.). Results: IC50 concentrations for treatment with calcitriol, across the 16 cell lines ranged from 0.12 µM to > 100 µM, using the MTT assay. These IC50 values were validated by CFA with a significant correlation between the 2 assays (p = 0.0046, r = 0.898). Sensitivity to calcitriol was higher in ER+ compared to ER- cell lines (p = 0.0454) but was independent of HER2 status (p = 0.8181). VDR expression in the cell lines varied from undetectable to 10 pg/mg. A significant correlation was found between VDR levels and IC50 value (p = 0.0076, r = -0.6401). IC50 concentrations for treatment with the low calcemic-inducing VD analogue inecalcitol ranged from 4.2 nM to 54.4 nM across 7 cell lines. Sensitivity to inecalcitol was higher in ER+ compared to ER- cell lines (p = 0.0092), but like with calcitriol, was independent of HER2 status (p = 0.4745). A significant correlation was found between IC50 values for inecalcitol and calcitriol (p = 0.0231, r = 0.8571). However, depending on the cell line, inecalcitol was approximately 14 to > 50 fold more sensitive than calcitriol (p = 0.0006). Conclusions: These preclinical results suggest that calcitriol and inecalcitol can inhibit breast cancer cell line growth. Since inecalcitol, is considerably more potent than calcitriol and has low calcemic potential, it should be further investigated as a treatment for breast cancers expressing VDR.
MULTIVESSEL VERSUS CULPRIT-ONLY PCI IN PATIENTS WITH NON-ST SEGMENT ELEVATION MYOCARDIAL INFARCTION AND MULTIVESSEL DISEASE: RESULTS FROM THE PROMETHEUS STUDY
Authors: Birgit Vogel, Usman Baber, Samantha Sartori, Jaya Chandrasekhar, Serdar Farhan, Michela Faggioni, Sabato Sorrentino, Annapoorna Kini, William Weintraub, Sunil Rao, Samir Kapadia, Sandra Weiss, Craig Strauss, Catalin Toma, J. Muhlestein, Anthony DeFranco, Mark Effron, Stuart Keller, Brian Baker, Stuart Pocock, Timothy Henry, Roxana Mehran
Journal: Journal of the American College of Cardiology (2017)
An open-label, randomized, phase II study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) given sequentially with ipilimumab in patients (pts) with advanced or metastatic melanoma (MEL).
Authors: F. Stephen Hodi, Christine Baudelet, Allen C. Chen, Jeffrey S. Weber
Journal: Journal of Clinical Oncology (2013)

TPS9107^ Background: Programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) are immune checkpoint receptors that attenuate T-cell responses and contribute to immune evasion by tumor cells. Nivolumab is a PD-1 receptor blocking monoclonal antibody that has shown clinical activity in phase 1 trials with various tumor types including MEL. Ipilimumab is an anti-CTLA-4 monoclonal antibody approved for advanced or metastatic MEL. Preclinical data suggest that combined PD-1 and CTLA-4 receptor blockade may improve antitumor activity in MEL, with PD-1 blockade upregulating CTLA-4 expression and CTLA-4 blockade upregulating PD-1 expression on tumor-infiltrating T cells. We describe a phase II study evaluating nivolumab administered sequentially with ipilimumab in pts with advanced (unresectable stage III) or metastatic (stage IV) MEL. Methods: This open-label, phase II study will enroll approximately 80 pts. During the induction period, pts will be randomized 1:1 to either nivolumab (3 mg/kg, q2w) from Weeks (Wk) 1-13 followed by ipilimumab (3 mg/kg, q3w) from Wks 14-25, or ipilimumab followed by nivolumab at the same doses and schedules. All pts will then receive nivolumab (3 mg/kg, q2wk) during the continuation period until disease progression or unacceptable toxicity, for ≤2 years from initial study treatment. Pts may be treatment-naive or have disease recurrence or progression after one prior systemic therapy, excluding prior anti-PD-1, anti-CTLA-4, or a BRAF inhibitor. The primary endpoint is the incidence of treatment-related Grade 3–5 adverse events (AEs) during the induction period. Secondary endpoints are response rate at Wk 25 and progression rates at Wks 13 and 25. Exploratory endpoints include safety and tolerability; overall survival; pt-level time course of treatment-related grade 3–5 AEs, response, progression, treatment discontinuation, and death; the association of changes in pharmacodynamic immune markers from baseline to Wk 13 and Wk 25 and clinical response; the association between baseline immunological parameters and clinical response; and immune-related single nucleotide polymorphisms. Clinical trial information: NCT01783938.
Résections endoscopiques hautes chez les patients cirrhotiques: profil d'efficacité et de sécurité
Authors: C Miaglia, J Dumortier, O Guillaud, C Chambon-Augoyard, J Rivory, JC Saurin, T Ponchon, M Pioche
Journal: Endoscopy (2017)

La chirurgie abdominale est une procédure grevée d'un risque de complication important chez les patients cirrhotiques, notamment d'infection ou décompensation de cirrhose. La survenue de ces complications dépend du type de chirurgie, mais aussi du stade de la cirrhose. La résection gastrique par exemple peut présenter jusqu'à 78% de morbidité et 54% de mortalité. La prise en charge endoscopique des lésions précancéreuses et cancéreuses intramuqueuses du tube digestif permet un traitement efficace et sûr dans la population générale. Il n'existe cependant pas de données sur une cohorte de grande ampleur concernant les résultats chez les patients cirrhotiques, notamment en termes de réussite et de complication. Il est à craindre que l'hypertension portale, notamment au niveau de l'oesophage, ainsi que le risque de décompensation de cirrhose et d'infection puissent représenter un frein à la résection endoscopique (RE). Notre étude visait à évaluer l'efficacité carcinologique et la sécurité des RE, ainsi que les facteurs de risques de survenue de complication.
Phase (ph) 2 study of bortezomib ± docetaxel in previously treated patients (pts) with advanced non-small cell lung cancer (NSCLC): Preliminary results
Authors: M. P. Fanucchi, R. J. Belt, F. V. Fossella, R. B. Natale, F. Robert, P. Fidias, K. Kelly, O. Kashala, D. P. Schenkein, J. H. Schiller
Journal: Journal of Clinical Oncology (2004)

7107 Background: Tax, a microtubule stabilizer, is active against NSCLC. Bortezomib (VELCADE), a reversible proteasome inhibitor, has demonstrated activity against NSCLC in ph 1 trials. Vc + Tax had manageable, non-additive toxicities in a prior ph 1 trial. Vc + Tax is more potent than either agent alone in tumor models in mice. Methods: The primary objective of this randomized, multicenter, open-label, phase 2 study was determining tumor response to Vc ± Tax. Secondary objectives were safety, tolerability, survival, pharmaco-kinetics, -dynamics, and -genomics. Patients (pts) ≥18 yr, stage IIIB or IV NSCLC, KPS ≥70, 1 prior chemotherapy regimen, no previous Vc or Tax, were randomized to Vc alone (Arm A) or Vc + Tax (Arm B). Arm A pts received Vc 1.5 mg/m2 IV on d 1, 4, 8, and 11 q21d. Arm B pts received dexamethasone premedication, Tax 75 mg/m2 IV on d 1, and Vc 1.3 mg/m2 on d 1, 4, 8, and 11 q21d. Treatment continued until PD, CR, or occurrence of unacceptable adverse event (AE). Objective responses per RECIST were scored as CR, PR, SD, or PD. Results: Initial data are available on 53 (of 155 planned) pts enrolled from 12/02–9/03 (Arm A: n = 27; Arm B, n = 26). >50% pts received ≥2 cycles. AE were similar in both arms except as noted. Grade (G) 3/4 AE occurred in 28/53 (53%) pts, and were mainly neutropenia (10 pts, Arm B only), respiratory (7 pts), gastrointestinal (6 pts), and fatigue (5 pts, Arm B only). Of all drug-related AE, nausea (34%), fatigue (28%), and neutropenia (23%) were most common, the latter 2 more frequent in Arm B. Ongoing interim analysis will be completed 12/31/03. Conclusions: Combination Vc + Tax was generally safe with manageable toxicity in pts with advanced NSCLC. Efficacy results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Pharmaceuticals, Inc. Aventis; Bristol-Myers Squibb; Millennium Pharmaceuticals, Inc.; Serono International Millennium Pharmaceuticals, Inc. Aventis; Bristol-Myers Squibb; Lilly; Serono International Millennium Pharmaceuticals, Inc. malpractice case
Identifications of Highly Aggressive Phenotype with SPI1 Overexpression in Pediatric T Cell Acute Lymphoblastic Leukemia/Lymphoma
Authors: Masafumi Seki, Shunsuke Kimura, Kenichi Yoshida, Tomoya Isobe, Hiroo Ueno, Hiromichi Suzuki, Yusuke Shiozawa, Keisuke Kataoka, Yoichi Fujii, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Masatoshi Takagi, Atsushi Iwama, Kentaro Oki, Motohiro Kato, Katsuyoshi Koh, Ryoji Hanada, Hiroshi Moritake, Ryoji Kobayashi, Takao Deguchi, Yoshiko Hashii, Toshihiko Imamura, Atsushi Sato, Keizo Horibe, Nobutaka Kiyokawa, Atsushi Manabe, Akira Ohara, Masashi Sanada, Yasuhide Hayashi, Hiroyuki Mano, Satoru Miyano, Akira Oka, Seishi Ogawa, Junko Takita
Journal: Blood (2016)
WHAT'S BEYOND MUSCULOSKELETAL INJURIES IN PROFESSIONAL FOOTBALL? A 1-YEAR PROSPECTIVE STUDY ON MENTAL WELL-BEING
Authors: Vincent Gouttebarge, Haruhito Aoki, Gino Kerkhoffs
Journal: British Journal of Sports Medicine (2017)

Background In contrast to the extensive amount of information available about their physical health, scientific knowledge about the mental well-being of professional footballers is scarce. In addition, the potential relation of musculoskeletal injuries with the mental well-being of professional footballers has not been studied yet. Objective To explore the mental well-being (distress, anxiety depression, sleep disturbance, adverse alcohol use) of professional footballers over twelve months and to assess its relation with musculoskeletal injuries. Design Observational prospective cohort study with a follow-up period of twelve months was conducted. Setting Professional football in five European countries: Finland, France, Norway, Spain and Sweden. Patients (or Participants) A total of 540 professional footballers were enrolled (mean age at recruitment was 27 years; mean career duration was 8 years; 55% from the highest national level). Interventions (or Assessment of Risk Factors) The total number of time-loss (&gt;4 weeks) injuries occurred during a player's career was examined by a single question. Main Outcome Measurements Distress, anxiety depression, sleep disturbance, adverse alcohol use were self-reported through validated scales. Results Among professional footballers, twelve-month incidence was 12% for distress, 37% for anxiety/depression, 19% for sleep disturbance and 14% for adverse alcohol use. At baseline, professional footballers who had sustained two or more time-loss injuries during their career were 2.5 to 3.5 times more likely to report distress, anxiety depression, sleep disturbance or adverse alcohol use. Conclusions A professional football team typically drawn from a squad of 25 players can expect in one season at least three players to struggle with their mental well-being. This study empowers the need of an interdisciplinary approach to the clinical care and support in professional football.
Overexpression of G protein-coupled receptor GPR87 promotes pancreatic cancer aggressiveness and activates NF-κB signaling pathway
Authors: Li Wang, Wei Zhou, Yunfeng Zhong, Yongbao Huo, Ping Fan, Sudong Zhan, Jun Xiao, Xin Jin, Shanmiao Gou, Tao Yin, Heshui Wu, Tao Liu
Journal: Molecular Cancer (2017)

Pancreatic cancer is a highly lethal disease and has the worst prognosis of any major malignancy. G protein-coupled receptor GPR87 is reported to be overexpressed in multiple cancers. The clinical significance and biological role of GPR87 in pancreatic cancer, however, remain to be established.GPR87 expression in pancreatic cancer cell lines, paired patient tissues were determined using western blotting and Real-time PCR. Ninety-six human pancreatic cancer tissue samples were analyzed by immunochemistry (IHC) to investigate the association between GPR87 expression and the clinicopathological characteristics of pancreatic cancer. Functional assays, such as anchorage-independent growth, chicken chorioallantoic membrane (CAM) assay, transwell matrix penetration assay, and Annexin V-FITC and PI staining and a xenograft tumor model were used to determine the oncogenic role of GPR87 in human pancreatic cancer progression. The effect of GPR87 on NF-κB signaling pathway was further investigated using the luciferase reporter assays, and by detection of the NF-κB signaling downstream genes.Herein, we reported that GPR87 was markedly overexpressed in pancreatic cancer cells and clinical tissues. Immunohistochemical analysis showed that the expression of GPR87 significantly correlated with patients' clinicopathologic features, including clinical stage and tumor-nodule-metastasis (TNM) classification. Pancreatic cancer patients with higher levels of GPR87 expression had shorter overall survival compared to patients with lower GPR87 levels. We gained valuable insights into the mechanism of GPR87 expression in pancreatic cancer cells by demonstrating that overexpressing GPR87 significantly enhanced, whereas silencing endogenous GPR87 inhibited, the proliferation, angiogenesis and increased resistance to gemcitabine-induced apoptosis of pancreatic cancer in vitro and tumorigenicity of pancreatic cancer cells in vivo. Finally, we demonstrated that GPR87 enhanced pancreatic cancer aggressiveness by activating NF-κB signaling pathway.Taken together, these findings suggest that GPR87 plays a critical oncogenic role in pancreatic cancer progression and highlight its potential as a target for pancreatic cancer therapy.Our findings suggest that GPR87 plays a critical oncogenic role in pancreatic cancer progression and highlight its potential as a target for pancreatic cancer therapy.
Somatic malignant differentiation in adult male germ-cell tumors (GCTs): Preliminary evidences from the <i>INTera</i> database (International Project for Teratoma with Malignant Transformation)
Authors: A. Necchi, M. Colecchia, N. Nicolai, M. Mego, U. De Giorgi, G. Mikuz, T. Sava, M. Di Nicola, U. Pastorino, R. Salvioni
Journal: Journal of Clinical Oncology (2009)

e16013 Background: Malignant transformation (MT) is a rare phenomenon characterized by a neoplastic somatic differentiation within a GCT. Little is known concerning its clinical implications. An international registry (INTera Project) has been established to collect all past and new cases worldwide. Methods: Patients (pts) with a MT within GCT have been retrospectively identified from registries of contributing Institutions. Significant clinical and pathological data have been collected and data files gathered at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. Results: 47 pts have been identified as well as a variety of 12 histologies. 25 pts had MT in primary tumor: 14 of them had no metastases (11 underwent primary retroperitoneal lymph-node dissection - RPLND), and 11 underwent chemotherapy (CT) ± surgery due to metastatic disease. All 14 pts with no metastases remain disease-free (DF) following a median follow-up (f-up) of 72 months (2–236+ months). 6 of 11 pts undergoing chemotherapy remain disease-free following a median f-up of 155 months (8–297+). 22 pts had MT in metastases only and 20 of them are evaluable. Following CT, 7 underwent radical surgery and 5 of them remain DF following a median f-up of 77 months (19–166+ months), while 13 could not undergo radical removal of disease, and 3 of them have been rescued by further CT and are DF at 37+, 41+ and 79+ months. So far, all 14 pts with no metastases as well as 7/9 (78%) who had radical removal of disease are alive and DF versus only 7/22 pts (32%) who could not receive a radical excision of residual masses. Median disease-free survival of pts with MT in primary only versus distant sites only was 54 (0–326+) and 2.5 (0–166+) months respectively (p=0.064 - at Log-rank test). No relevant outcome differences have been observed according to histology. Conclusions: Ongoing INTera project is a collaborative effort of MT case- collection worldwide. Stage of disease and radical surgery seem to associate with outcome. The growing number of cases and a centralized pathology review would help to increase knowledge on this rare disease. No significant financial relationships to disclose.