tbuckley/cabot-search huggingface dataset:
Phase I study of CNF1010 (lipid formulation of 17-(allylamino)-17-demethoxygeldanamycin: 17-AAG) in patients with advanced solid tumors
Authors: M. W. Saif, C. Erlichman, T. Dragovich, D. Mendelson, D. Toft, G. Timony, F. Burrows, C. Padgett, R. De Jager, D. Von Hoff
Journal: Journal of Clinical Oncology (2006)

10062 Background: 17-AAG is a benzoquinone ansamycin that binds to and inhibits the HSP90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. Methods: Patients (pts) with advanced solid tumors, ECOG PS 0–2, and adequate hematologic, hepatic, renal and cardiac functions received CNF1010 by 1 h intravenous infusion, twice-a-week, three weeks out of four, starting at 6 mg/m 2 per dose. Doses were escalated sequentially in single pts (6 and 12 mg/m 2 ) and 3–6 pts (≥ 25 mg/m 2 ) cohorts according to a modified Fibonacci’s schema. Plasma pharmacokinetic (PK) profiles were obtained on days 1 and 18. Biomarkers were measured in PBMC’s (HSP70) and plasma (HER-2 ectodomain (HER-2 ECD)). Results: 30 pts (M/F: 14/16; median age 63, range 48–78) with colorectal cancer (11), pancreatic cancer (5), melanoma (5), ovarian (2), others (7) were treated with a median of 2 courses (range: 1–10). There was no dose-limiting toxicity up to 175 mg/m 2 . One pt at 175 mg/m 2 died on study, but drug relation was unclear. Grade 1–2 gastrointestinal toxicities (nausea, vomiting, diarrhea) and serum creatinine elevation were observed. Severe toxicities (grade 3 but no grade 4) consisted of reversible hepatic enzyme elevation, hyperbilirubinemia, fatigue, anemia and hyperglycemia. There were no hematological toxicities. Plasma 17-AAG PK appeared dose-proportional (AUC, Cmax); CL (17 L/h/m 2 ) and t 1/2 (5.2 h) were dose independent and unchanged after repeated dosing (day 18). Post-treatment increases in HSP70 were observed in PBMCs and decreases in plasma HER-2 ECD were observed at doses ≥ 83 mg/m 2 . Minor tumor regressions were seen in 1 pt with duodenal cancer (83 mg/m 2 ), 1 pt with gastric carcinoid (175 mg/m 2 ) and 1 pt with melanoma (175 mg/m 2 ). Conclusion: The threshold of biologic activity for CNF1010 administered by a twice a week schedule appears to be 83 mg/m 2 . This dosing regimen appears to be optimal and supported by the pharmacokinetic and pharmacodynamic data. The MTD has not yet been determined. Dose escalation of CNF1010 continues at 225 mg/m 2 . [Table: see text]
IMPACT OF MODERATE AORTIC STENOSIS IN PATIENTS WITH SYSTOLIC HEART FAILURE
Authors: Guillaume Jean, Nicolas Van Mieghem, Elise Mara Vollema, Lennart van Gils, Victoria Delgado, Ernest Spitzer, Ikram El Azzouzi, Jeroen Bax, Philippe Pibarot, Marie-Annick Clavel
Journal: Journal of the American College of Cardiology (2020)
Cancer patients’ information needs in Nigeria.
Authors: Kenneth Chima Nwankwo, Emmanuel Ezeome
Journal: Journal of Clinical Oncology (2012)

e19572 Background: The attitudes of Nigerian cancer patients on cancer diagnosis and prognosis were studied to ascertain what diagnostic and prognostic information were disclosed to them by their physicians, and what they wanted to know about their cancer diagnosis and prognosis. Methods: Structured questionnaires were administered on all consenting cancer patients that were managed at the University of Nigeria Teaching Hospital Enugu (UNTH-E) between July and October 2011. The data collected were analyzed with Statistical Package for Social Sciences (SPSS) software version 18. Results: Two hundred and forty four (244) patients participated in the study. While 95% of the participants wanted to know the nature of their diagnosis, only76.7% admitted to being informed of the diagnosis by their doctors. Nearly 54% of participants will like to be informed of a bad prognosis when death is imminent. The word “cancer” was used to disclose the diagnosis to 69.4% of the patients. Hundred and eight (44.3%) of the patients did not have any idea what “cancer” meant or did not know how to explain it while 39.8% knew it as a deadly, incurable or a painful disease and 8.6% described it as a tumour or abnormal growth. The nature of the disease was explained to 155(66.0%) of the patients among whom 114(76%) felt they received adequate or more than adequate explanation of their cancer to enable them undergo treatment. Patient factors that significantly improved the disclosure of diagnostic information were education (p=0.044) and site of the cancer (p=0.043). There was no statistically significant association between the desire for diagnostic and prognostic information and the patients’ age, gender, educational attainment or site of the cancer. Conclusions: Most of the surveyed cancer patients in Nigeria desire to know the truth about the diagnosis of their disease and more than 50% of them desire to know when the cancer stage becomes terminal and death imminent. Physicians in Nigeria should consider the information needs of the individual patients and satisfy them.
The Circular RNA circSKA3 Binds Integrin β1 to Induce Invadopodium Formation Enhancing Breast Cancer Invasion
Authors: William W. Du, Weining Yang, Xiangmin Li, Ling Fang, Nan Wu, Feiya Li, Yu Chen, Qihan He, Elizabeth Liu, Zhenguo Yang, Faryal Mehwish Awan, Mingyao Liu, Burton B. Yang
Journal: Molecular Therapy (2020)

Metastatic cancer cells invade surrounding tissues by forming dynamic actin-based invadopodia, which degrade the surrounding extracellular matrix and allow cancer cell invasion. Regulatory RNAs, including circular RNA, have been implicated in this process. By microarray, we found that the circular RNA circSKA3 was highly expressed in breast cancer cells and human breast cancer tissues. We further found that the invasive capacity of breast cancer cells was positively correlated with circSKA3 expression, through the formation of invadopodia. Mechanistically, we identified Tks5 and integrin β1 as circSKA3 binding partners in these tumor-derived invadopodia. Ectopic circSKA3 expression conferred increased tumor invasiveness in vitro and in vivo. We further identified the RNA-protein binding sites between circSKA3, Tks5 and integrin β1. In tumor formation assays, we found that circSKA3 expression promoted tumor progression and invadopodium formation. Mutation of the circSKA3 binding sites or transfection with blocking oligos abrogated the observed effects. Thus, we provide evidence that the circular RNA circSKA3 promotes tumor progression by complexing with Tks5 and integrin β1, inducing invadopodium formation. Metastatic cancer cells invade surrounding tissues by forming dynamic actin-based invadopodia, which degrade the surrounding extracellular matrix and allow cancer cell invasion. Regulatory RNAs, including circular RNA, have been implicated in this process. By microarray, we found that the circular RNA circSKA3 was highly expressed in breast cancer cells and human breast cancer tissues. We further found that the invasive capacity of breast cancer cells was positively correlated with circSKA3 expression, through the formation of invadopodia. Mechanistically, we identified Tks5 and integrin β1 as circSKA3 binding partners in these tumor-derived invadopodia. Ectopic circSKA3 expression conferred increased tumor invasiveness in vitro and in vivo. We further identified the RNA-protein binding sites between circSKA3, Tks5 and integrin β1. In tumor formation assays, we found that circSKA3 expression promoted tumor progression and invadopodium formation. Mutation of the circSKA3 binding sites or transfection with blocking oligos abrogated the observed effects. Thus, we provide evidence that the circular RNA circSKA3 promotes tumor progression by complexing with Tks5 and integrin β1, inducing invadopodium formation.
The microstructure of REM sleep: Why phasic and tonic?
Authors: Péter Simor, Gwen van der Wijk, Lino Nobili, Philippe Peigneux
Journal: Sleep Medicine Reviews (2020)

Rapid eye movement (REM) sleep is a peculiar neural state that occupies 20–25% of nighttime sleep in healthy human adults and seems to play critical roles in a variety of functions spanning from basic physiological mechanisms to complex cognitive processes. REM sleep exhibits a plethora of transient neurophysiological features, such as eye movements, muscle twitches, and changes in autonomic activity, however, despite its heterogeneous nature, it is usually conceptualized as a homogeneous sleep state. We propose here that differentiating and exploring the fine microstructure of REM sleep, especially its phasic and tonic constituents would provide a novel framework to examine the mechanisms and putative functions of REM sleep. In this review, we show that phasic and tonic REM periods are remarkably different neural states with respect to environmental alertness, spontaneous and evoked cortical activity, information processing, and seem to contribute differently to the dysfunctions of REM sleep in several neurological and psychiatric disorders. We highlight that a distinctive view on phasic and tonic REM microstates would facilitate the understanding of the mechanisms and functions of REM sleep in healthy and pathological conditions.
HEPATIC STEATOSIS, CARDIOMETABOLIC HEALTH AND OUTCOMES IN PATIENTS UNDERGOING CORONARY ARTERY CALCIUM (CAC) SCORING
Authors: Jared Durieux, Gina Anderson, Jennifer Sposato, Ahmad Tarek Chami, Imran Rashid, Robert C. Gilkeson, Sadeer Al-Kindi, Sanjay Rajagopalan
Journal: Journal of the American College of Cardiology (2020)
Dose escalation of doxorubicin hydrochloride and ifosfamide in previously untreated Ewing sarcoma.
Authors: Muhammad Memon, Madras A. Raja, Javed Ahmad, Rajive Pant, Mahmoud Shaheen, Fouad Al-Dayel
Journal: Journal of Clinical Oncology (2012)

e20508 Background: Ewing’s sarcoma is a primary malignant tumour of the bone. Ifosfamide and doxorubicin hydrochloride are two active drugs. Administration of the maximum feasible doses may help achieve the best result. In this study we proposed to use the combination of vincristine, actinomycin D, doxorubicin hydrochloride, ifosfamide (VAAI) for total of 12 cycles. Methods: All eligible patients will receive initially four cycles of VAAI. Doses include: vincristine maximum 2 mg IV doxorubicin hydrochloride 25 mg/m 2 IVpush for 3 days ifosfamide 3 Gm/m 2 as an intravenous infusion over 2 hours for 3 days. Each cycle will be repeated every 21 days. Patient will then undergo response evaluation, and subjected to surgical resection when posible. If surgery is incomplete, not possible or refused, radical radiation therapy to a dose of 55 Gy was given. Post operatively patient will recice two cycle of adriamycin base chemotherapy and than will continue with actinomycin d to complete 12 cycles. Results: 16 patients were enroll, mean age 19 years range 15-35, male/female 9/7, tumor location pelvis 3 femur 5 tibia 1 humrus 2 foot 2 maxilla 1 radius 1 extra skeletal at thigh 1. After the enrolment of three patients, there was frequent incidence of febrile neutropenia and mucositis, dose of ifofamide was reduce to 2.25 gm/m2 and GCSF was added. Out of 16 patients enrolled, 5 patients withdrew (1 recurrent febrile neutropenia, 2 disease progression, 1 delay of chemotherapy more than 3 weeks and 1 was rediagnosed post 4 cyles and surgert as synovial sarcoma). 9 patients received all 12 cycles of chemotherapy (5 patients needed further dose reduction of ifofamide by 20% as per protocol, and 2 patients received 11 cycles. There was no toxic death. 8 patients had mild to moderate mucositis, nausea and vomiting grade 2 in 4 patients and in 3 grade 3.10 patients underwent surgical resection of tumor and 8 patient received radiation therapy. 8 patient achieve complete remission. Conclusions: This is a unique study that all the patient enrolls were more than 14 years, this combination of chemotherapy was well tolerated, had good feasibility and easily manageable toxicity and can be administered as a outpatient. To the best of our knowledge this is the first study using this chemotherapy as outpatient.
A phase II trial of paclitaxel plus carboplatin in patients with non-small cell lung cancer previously treated with chemotherapy
Authors: K. Yoh, K. Kubota, R. Kakinuma, H. Ohmatsu, K. Goto, S. Niho, Y. Nishiwaki, N. Saijo
Journal: Journal of Clinical Oncology (2006)

17103 Background: The purpose of this phase II trial was to evaluate the efficacy and toxicity of paclitaxel plus carboplatin in the treatment of advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Methods: Eligible patients were aged 20 to 75 years with a performance status (PS) 0 to 1, previous treatment with one or two prior chemotherapy regimen for advanced NSCLC, and adequate organ function. Paclitaxel 200 mg/m 2 was infused over 3 hours, before carboplatin (area under the curve 6; Calvert formula) infused over 1 hour, once every 3 weeks for six cycles maximum. The primary endpoint of this study was response rate. Simon’s two-stage design was used to determine the sample size and the planned accrual was 30 patients. Results: Thirty patients were enrolled. Complete response was observed in one patient and partial response in eleven patients for an overall response rate of 40% (95% confidence interval: 23–59%). The median time to progression was 5 months. The median survival was 9.9 months (range, 2.5–33.8 months), and the 1-year survival rate was 46%. The hematologic toxicities were 7% for grade 4 neutropenia, 3% for grade 3 febrile neutropenia, 17% for grade 3 and 4 anemia, and 7% for grade 3 thrombocytopenia. Grade 3 non-hematologic toxicities included rash (7%), myalgia/arthralgia (3%), arrhythmia (3%), and infection (3%). There were no toxic deaths. Conclusions: The combination of paclitaxel plus carboplatin is an active and well-tolerated regimen in the treatment of patients with NSCLC previously treated with chemotherapy who have a good PS. No significant financial relationships to disclose.
Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFβ signalling
Authors: David E Ebeid, Farid G Khalafalla, Kathleen M Broughton, Megan M Monsanto, Carolina Y Esquer, Veronica Sacchi, Nirmala Hariharan, Kelli I Korski, Maryam Moshref, Jacqueline Emathinger, Christopher T Cottage, Pearl J Quijada, Jonathan H Nguyen, Roberto Alvarez, Mirko Völkers, Mathias H Konstandin, Bingyan J Wang, Fareheh Firouzi, Julian M Navarrete, Natalie A Gude, Marie-Jose Goumans, Mark A Sussman
Journal: Cardiovascular Research (2020)

Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 is a cardioprotective kinase that antagonizes the aging phenotype of cardiomyocytes and delays cellular senescence by maintaining telomere length, but the mechanism remains unknown. Another pathway responsible for regulating telomere length is the transforming growth factor beta (TGFβ) signalling pathway where inhibiting TGFβ signalling maintains telomere length. The relationship between Pim1 and TGFβ has not been explored. This study delineates the mechanism of telomere length regulation by the interplay between Pim1 and components of TGFβ signalling pathways in proliferating A549 cells and post-mitotic cardiomyocytes.
PACEMAKER IMPLANTATION FOLLOWING TAVR: USING MACHINE LEARNING TO OPTIMIZE RISK STRATIFICATION
Authors: Vien T. Truong, Matthew Wigle, Emma Bateman, Akhil Pallerla, Tam N.M. Ngo, Daniel Beyerbach, Dean Kereiakes, Satya Shreenivas, Justin Tretter, Cassady Palmer, Wojciech Mazur, Eugene Chung
Journal: Journal of the American College of Cardiology (2020)
Association of Rs1139971, a KAI1 polymorphism, with bone metastasis progression in prostate cancer and ganglionnary metastasis.
Authors: Marie Audouin, Géraldine Cancel Tassin, Cécile Gaffory, Valérie Ondet, Stephane Oudard, Abdel Rahmene Azzouzi, Morgan Roupret, Olivier Cussenot
Journal: Journal of Clinical Oncology (2013)

e16089 Background: Metastatic prostate cancer, with bones as principal location, is responsible for most of the death from this malignancy. If the molecular mecanisms of the metastasis progression are not completely solved, many involved pathways have been clarified. Association studies have proven that genetic factors could affect the risk of prostate cancer or its agressiveness. Likewise, some polymorphisms from genes involved in metastatic pathways could have a meaningfull function in the individual genetic susceptibility to metastatic prostate cancer. The KAI1 gene is known to be implicated in the metastatic process of many malignant tumors, such as breast, lung or colorectal cancer. Moreover, the protein encoded by this gene seems to act as a metastatic suppressor. In this study, we searched for an association between the risk of metastatic progression and a polymorphism from the KAI gene (rs1139971). Methods: It was a retrospective and multicentrique study, comparing 195 patients harbouring bone and/or ganglionnary metastatic prostate cancer with 386 patients affected by a non metastatic prostate cancer. All the patients were caucasians. The variant rs1139971 has been genotyped by Taqman technology. Results: The allele A from rs1139971 was found to be less frequent in metastatic patients but this result wasn’t significant. The patients were then stratified according to the metastatic location : bone or ganglionnary. In this case, the allele A was significantly associated with metastatic risk in the group of patients with bone metastasis [OR = 0,525 ; IC 95% = 0,332-0,828 ; p = 0,0056]. Conclusions: In this study, a significant association has been pointed up between bone metastatic prostate cancer and the polymorphism rs1139971 from KAI1 gene. However, these results need to be confirmed on a larger and independant population.
ASSOCIATION BETWEEN AFRICAN AMERICAN RACE AND POORER OUTCOMES AFTER MYOCARDIAL INFARCTION
Authors: Mariana Garcia, Zakaria Almuwaqqat, Bruno Lima, Samaah Sullivan, Belal Kaseer, An Young, Kasra Moazzami, Amit J. Shah, Tene Lewis, Muhammad Hammadah, Oleksiy Levantsevych, Lisa Elon, Ernest Garcia, Doug Bremner, Paolo Raggi, Arshed A. Quyyumi, Viola Vaccarino
Journal: Journal of the American College of Cardiology (2020)
Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study
Authors: Yingzhen Du, Lei Tu, Pingjun Zhu, Mi Mu, Runsheng Wang, Pengcheng Yang, Xi Wang, Chao Hu, Rongyu Ping, Peng Hu, Tianzhi Li, Feng Cao, Christopher Chang, Qinyong Hu, Yang Jin, Guogang Xu
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.
ASSOCIATION BETWEEN THE INDUCTION OF SELF CARE MANAGEMENT SYSTEM AND LONG-TERM OUTCOMES IN PATIENTS HOSPITALIZED FOR HEART FAILURE
Authors: Eisaku Nakane, Takao Kato, Nozomi Tanaka, Tomoari Kuriyama, Kouki Kimura, Shushi Nishiwaki, Toka Hamaguchi, Yusuke Morita, Yuhei Yamaji, Yoshisumi Haruna, Tetsuya Haruna, Moriaki Inoko
Journal: Journal of the American College of Cardiology (2020)
Abstract 12876: Aortic Stiffening is More Rapid in Bav Than in Genetic Aortopathies and is Associated With Rate of Aortic Dilation
Authors: Alejandro Perez Casares, Kimberlee Gauvreau, Audrey Dionne, Ashwin Prakash
Journal: Circulation (2019)

Introduction: Bicuspid aortic valve (BAV) is an aortopathy associated with aortic dilation. In other genetically mediated connective tissue disorders (CTDs), lower aortic distensibility is associat...
IN-HOSPITAL ACUTE ISCHEMIC STROKE FOLLOWING ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Aiham Albaeni, Ché Matthew Harris, Hesham Nasser, Sirhley Sifontes, Sai Guduru, Khalid Abusaada, Khaled Chatila, Syed Gilani, Wissam I. Khalife
Journal: Journal of the American College of Cardiology (2020)
Incidence of reversible amenorrhea in women with early-stage breast cancer undergoing adjuvant anthracyclin-based chemotherapy with or without docetaxel
Authors: M. Berliere, F. Dalenc, N. Malingret, A. Vindevogel, J. Kerger, H. Roche, M. Symann, J. Donnez, J. Machiels P
Journal: Journal of Clinical Oncology (2006)

10517 Background: The objective of this study was to determine the incidence of reversible amenorrhea in women with early-stage breast cancer undergoing adjuvant anthracyclin-based chemotherapy with or without docetaxel. Methods: We studied the amenorrhea duration induced by 2 chemotherapy regimens. The first arm (6FEC) consisted in the administration of 6 cycles of FEC100 (5-Fluorouracil 500 mg/m 2 , Epirubicin 100 mg/m 2 , Cyclophosphamide 500 mg/m 2 , day 1, every 3 weeks) and the second arm (3FEC/3D) in the administration of 3 cycles of FEC100 followed by 3 cycles of Docetaxel (100 mg/m 2 , day 1, every 3 weeks). Some of these patients (N = 121, 78%) were treated in the PACS01 trial that was designed to evaluate the impact of the sequential addition of docetaxel to FEC100 on disease-free survival for patients with node positive, operable breast cancer. Other patients (N = 33.22%) were patients treated with the same regimens after the inclusion period of PACS01. Reversible amenorrhea was defined as a recovery of regular menses and -when available (101 patients)- premenopausal hormonal values (minimum 2 tests at 3 months interval) in the year following the end of chemotherapy infusion. Results: 154 pre-menopausal patients were included: 84 were treated in the 6FEC and 70 in the 3FEC/3D. Median age was 43.5 (28–58) and 44 (29–53), respectively. The incidence of chemotherapy-induced amenorrhea at the end of chemotherapy was not different between the two groups, 6FEC: 93% and 3FEC/3D: 92.5%. In the year following the end of chemotherapy, more patients recovered regular menses in the 3FEC/3D arm compared to the 6FEC arm: 35.5% (25/70) versus 23.7% (20/84) (p = 0.019). For the 101 for which hormonal values were available, more patients recovered premenopausal hormonal values in the 3FEC/3D arm: 42% (18/42) versus 29% (17/59) (p &lt; 0.01). Conclusions: Our study suggests that it could be interesting to record the menopausal status at different time points after the end of chemotherapy. In addition, the survival advantage in the PACS01 trial in favor of the 3FEC/3D arm was observed only for women over the age of 50 and not for women younger than 50. In this context, the clinical relevance of reversible amenorrhea warrants further investigation. No significant financial relationships to disclose.
TRANSCATHETER AORTIC VALVE REPLACEMENT OUTCOMES IN PATIENTS WITH NATIVE AORTIC VALVE INSUFFICENCY
Authors: Andres Jadue, John Cyril Lisko, Jose Francisco Condado Contreras, Norihiko Kamioka, Vasilis Babaliaros, Adam Greenbaum, Gaetano Paone, Isida Byku, Robert Guyton, Aneesha Maini, Chandan Devireddy, Kendra Grubb
Journal: Journal of the American College of Cardiology (2020)