tbuckley/cabot-search huggingface dataset:
Validation of the NCI patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in women receiving treatment for metastatic breast cancer.
Authors: Sandra A. Mitchell, Kathy Lang, Christine Nichols, Steven B. Clauser, Victoria Federico, Deepa Lalla, Debu Tripathy, Sara A. Hurvitz, Kathleen M. Castro, Bryce B. Reeve, Lauren J. Rogak, Andrea Denicoff, Alice Chen, Richard Piekarz, Antonia V Bennett, Thomas Michael Atkinson, Ann M. O'Mara, Lori M. Minasian, Ethan M. Basch
Journal: Journal of Clinical Oncology (2012)

9144 Background: NCI PRO-CTCAE is designed to enhance adverse event reporting by integrating patients’ self-report of the frequency (F), severity (S) and interference (I) with usual activities of 78 symptomatic treatment toxicities. This study examined the construct validity of a subset of PRO-CTCAE items in women with metastatic breast cancer (MBC). Methods: 207 women (70% aged 45-59 years; 94% White;71% college-educated) with HER2+ MBC who had received treatment in the past month were recruited from 6 U.S. breast cancer support groups and completed a web survey that collected 18 PRO-CTCAE symptoms, and the Rotterdam Symptom Checklist (RSC). Pairwise concordance among PRO-CTCAE symptom dimensions was examined using weighted Kappa and Bowker’s test for symmetry. Results: Respondents were a median of 47 months since MBC diagnosis and 61% rated their health-related quality of life (HRQL) as good to excellent. Symptom prevalence was similar for PRO-CTCAE and RSC, with respondents more likely to endorse mood disturbance on PRO-CTCAE (Anxiety/Worry 90%; Sad/Unhappy Feelings 86%) vs. RSC (Anxiety 63%; Depressed Mood 61%). There was parallel rank-ordering of fatigue, anxiety, insomnia, depression, difficulty concentrating and neuropathy as the symptoms that were most severe, interfered most and caused the greatest bother. Within PRO-CTCAE, pairwise agreement among F, S and I was moderate for most symptoms (κ w =.42 to .54). Agreement between F and S was highest for pain, nausea and arm/leg swelling (κ w =.61 to .80), and lowest for anxiety/worry and sad/unhappy feelings (κ w = .27-.37). Except for arm/leg swelling, endorsement patterns by the dimensions of F, S and I were distinct (Bowker’s p all &lt;.002). Across PRO-CTCAE symptoms, S was consistently higher than I (mean differences .12 to .72, all p&lt;.01]). Means for S were consistently and significantly higher for those with impaired versus preserved HRQL, providing evidence of construct validity. Conclusions: This study supports the construct validity of PRO-CTCAE, and suggests that F, S and I dimensions offer non-overlapping information relative to 17 /18 PRO-CTCAE symptomatic toxicities.
Human α1 type IV collagen NC1 domain exhibits distinct antiangiogenic activity mediated by α1β1 integrin
Authors: Akulapalli Sudhakar, Pia Nyberg, Venkateshwar G. Keshamouni, Arjuna P. Mannam, Jian Li, Hikaru Sugimoto, Dominic Cosgrove, Raghu Kalluri
Journal: Journal of Clinical Investigation (2020)

The amino acid substitution for the ALAS2 mutation was incorrectly noted in the original article.The correct designation is ALAS2 Y365H.
Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map
Authors: Omer Ali Bayraktar, Theresa Bartels, Staffan Holmqvist, Vitalii Kleshchevnikov, Araks Martirosyan, Damon Polioudakis, Lucile Ben Haim, Adam M. H. Young, Mykhailo Y. Batiuk, Kirti Prakash, Alexander Brown, Kenny Roberts, Mercedes F. Paredes, Riki Kawaguchi, John H. Stockley, Khalida Sabeur, Sandra M. Chang, Eric Huang, Peter Hutchinson, Erik M. Ullian, Martin Hemberg, Giovanni Coppola, Matthew G. Holt, Daniel H. Geschwind, David H. Rowitch
Journal: Nature Neuroscience (2020)
A SYSTEMATIC POOLED ANALYSIS OF PUBLISHED STUDIES COMPARING COMPLICATION RATES BETWEEN TRANSVENOUS PACEMAKERS AND MICRA LEADLESS PACEMAKERS WITHIN THE MANUFACTURER AND USER FACILITY DEVICE EXPERIENCE DATABASE
Authors: Brian Liu, Malik Bilal Ahmed, Brian McCauley, Anshul Parulkar, Wasiq Sheikh, Esseim Sharma, Lauren Ashley Rousseau, Antony Chu
Journal: Journal of the American College of Cardiology (2020)
Phase I trial of ixabepilone and vorinostat in metastatic breast cancer.
Authors: Thehang H. Luu, Suzette Blanchard, Jan Hendrik Beumer, Bean N. Anyang, George Somlo, Joanne E. Mortimer, Arti Hurria, Lixin Yang, Yun Yen
Journal: Journal of Clinical Oncology (2012)

1070 Background: VOR, an HDAC inhibitor, induces acetylation of tubulin, and decreases resistance by attenuating downstream activation of AKT, c-Raf and HER-2. Patients (pts) with MBC treated with VOR had a TTP of 8.5 months (range 4-14) and stable disease in 29% (Luu et al., 2008). Our preclinical data showed synergistic effect of IXA and VOR in MDA-MB-231 and MCF7. Methods: The primary aims were to: 1) define the maximum tolerated dose (MTD) based on dose limiting toxicities (DLT), and 2) describe the pharmacokinetics (PK) of 2 schedules of VOR and IXA. Secondary aims were to describe: 1) response rate (RR) and 2) clinical benefit rate (CBR). The study included: 1) pts with MBC; 2) ECOG PS 0-2; 3) adequate marrow and organ functions; 4) no prior IXA or VOR; and 5) &lt; grade (gr) 1 neuropathy. Stable brain metastasis were allowed. Pts were randomized to schedule A: VOR (QDx14) + IXA (D2) Q21D; or B: VOR (D1-7 and 15-21) + IXA (D2, 9, 16) Q28D. A modified toxicity probability interval design (target toxicity rate= 0.2 and equivalence range +/- 0.05) (Ji et al, 2010) determined dose escalation guidelines. PK were assessed with LC-MS/MS assays. Results: Among 37 pts randomized, 36 were evaluable [median age (55 yrs); median prior chemotherapy regimens (3); ER and/or PR + (64%); HER2 + (19%)]. In cohort A, 16 pts were treated (1 inevaluable). The MTD was: VOR 300mg (QDx14) + IXA (32mg/m 2 D2) Q21D (dose level 1). DLT was experienced by 27% (4/15) pts [gr 4 neutropenia, gr 3 fatigue/AST, hyponatremia and allergic reaction to IXA]. In cohort B, 21 pts were treated (dose level 1, n=15; dose level 2, n=6). The MTD was VOR 300mg QD (D1-7 and 15-21) + IXA 16mg/m 2 (D2, 9, 16) Q28D (dose level 1), no DLTs were observed. Dose level 2 was closed with 50% (3/6) of pts experiencing DLTs [gr 3 neutropenia, hypertension, and hypokalemia]. Median cycles treated (cohort A: 6, cohort B: 4). Response in cohort A and B respectively was: 1 CR, 2 PR, 7 SD (RR: 20%, CBR: 67%) and 1 CR, 4 PR, 9 SD (RR: 33%, CBR: 93%). VOR and IXA PK were not influenced by the presence of the other drug, clearance values= 220 L/h and 20 L/h/m 2 , respectively. Conclusions: We established the MTD of VOR and IXA in pts with MBC. The combination demonstrated clinical activity in these heavily pretreated pts. Further studies are recommended.
CLO20-042: The HER2 FISH Ratio is a Predictor of Pathologic Complete Response Among Patients With HER2+ Breast Cancer Receiving Neoadjuvant Anti-HER2 Doublet Therapy Without Chemotherapy
Authors: Eric Lander, Ruey Hu, Katherine Rappazzo, Heidi Chen, Vandana Abramson
Journal: Journal of the National Comprehensive Cancer Network (2020)

"CLO20-042: The HER2 FISH Ratio is a Predictor of Pathologic Complete Response Among Patients With HER2+ Breast Cancer Receiving Neoadjuvant Anti-HER2 Doublet Therapy Without Chemotherapy" published on 20 Mar 2020 by National Comprehensive Cancer Network.
Phase II randomized study of gefitinib alone or plus vinorelbine every 2 weeks’ treatment in patients with adenocarcinoma of the lung who failed at least two regimens
Authors: Y. Chen, R. Perng, C. Tsai, J. Whang-Peng
Journal: Journal of Clinical Oncology (2006)

17095 Background: To assess the feasibility and the efficacy of adding chronic intermittent low-dose vinorelbine to gefitinib (Iressa) treatment for lung cancer patients with adenocarcinoma who failed 2 previous regimens of chemotherapy. Methods: Patients who had adenocarcinoma and failed at least 2 regimens, including taxanes and platinum, were enrolled and randomized into 2 arms: oral Iressa 250 mg daily (I) or vinorelbine 15 mg/m 2 intravenous infusion day 1 and oral Iressa 250 mg daily from day 2 to 14, every 2 weeks (IV). From August 2004 to October 2005, 48 patients were enrolled. Results: Twenty-four patients were randomized into Iressa plus vinorelbine treatment. However, 3 patients refused vinorelbine treatment and received Iressa treatment only. Thus, 27 patients received I treatment and 21 patients received IV treatment. Objective response rates were 55.6% in I and 57.1% in IV. Any grade of leukopenia, neutropenia, and fatigue sensation was significantly higher in the IV arm (p=0.035, 0.001, 0.012, respectively). All the toxicities in both arms were generally mild and no toxic death occurred. However, many patients in the IV arm stopped V treatment before disease progression, including port-A occlusion in 4 patients (after 2, 5, 20, and 23 injections, respectively), mucositis in 1 (after 4 injections), and fatigue sensation in 1 (after 7 injections). After a median follow-up of 8 months, median time to disease progression was higher in IV than I (longer than 12 months vs. 7.1 months, p = 0.0271), more than half of the patients in each arm were still alive (p = 0.2269), and more than 9 patients in each arm survived longer than 1 year. Conclusions: Iressa is highly effective in ethnic Chinese patients with adenocarcinoma of the lung who have failed previous platinum and taxane treatment. The addition of low-dose V every 2 weeks produced a signiificantly better progression-free survival. Replacement of intravenous V with oral V should be considered to prevent the early termination of V treatment. No significant financial relationships to disclose.
Oxygen Therapy for the Critically Ill
Authors: Derek C. Angus
Journal: New England Journal of Medicine (2020)

The administration of supplemental oxygen is one of the world’s most used therapies and is a cornerstone of care in the intensive care unit (ICU). The primary rationale is to avoid hypoxemia in patients with, or at risk for, impaired pulmonary gas exchange. Oxygen is generally considered to be widely available (which may not be true in less developed countries), inexpensive, and very safe. Consequently, it is typically administered liberally with an upward titration of the fraction of inspired oxygen (Fio2) to achieve a high level of arterial oxygen saturation (e.g., >96%), with less attention on avoidance of excess use. . . .
Eukaryotic elongation factor 1 alpha 2 alone is not sufficient to cause tumorigenicity in immortalized and neoplastic ovarian cell lines
Authors: A. L. Leiser, N. Rosales, D. Spriggs
Journal: Journal of Clinical Oncology (2006)

15051 Background: EEF1a2 is amplified and overexpressed in 25% of ovarian tumors. Previous studies have shown EEF1a2 to have oncogenic and tumorigenic properties in rodent fibroblasts. However, its role in the tumorigenesis and behavior of human ovarian carcinomas is not known. Methods: Stable expression of EEF1a2 cDNA in both T80 immortalized human ovarian surface epithelial cells and SKOV-3 cell line was followed by standard proliferation assays, soft agar assays for anchorage independent growth, cell cycle analysis, mouse xenograft injections, evaluation for changes in factors such as VEGF and ras and susceptibility to CDDP. Transient transfections with 3 different siRNA’s to EEF1a2 were performed in both cell lines. Results: Stable expression of EEF1a2 was detected by Western Blot and IP. Compared to vector only control, transfection with pCMVTag2B EEF1a2 vector did not change proliferation in either cell line. Anchorage independent growth was slightly higher in the T80 transfected cells. Cell cycle and expression of VEGF and ras were not different than control. IC 50 of CDDP was similar between the transfected and control cell lines. No size difference was seen in SKOV transfected and control xenografts. T80 controls grew larger and more frequent tumors than transfected controls. Transient transfection of T80 with siRNA did not result in changes in anchorage independent growth. Conclusion: EEF1a2 alone is not sufficient to act induce tumorigenicity, affect tumor growth rate or drug susceptibility in human ovarian epithelial cells. Experiments utilizing stable siRNA vectors specific to EEF1a2 are underway, as well the combination of EEF1a2 with recognized ovarian tumor oncogenes. No significant financial relationships to disclose.
Findings requiring immediate surgery in blunt abdominal trauma patients with isolated free fluid without solid organ injury on abdominal computed tomography: Retrospective laboratory, clinical and radiologic analysis. A case control study
Authors: Pil Young Jung, Eung Joo Park, Hongjin Shim, Ji Young Jang, Keum Seok Bae, Seongyup Kim
Journal: International Journal of Surgery (2020)
ACCURACY OF IMPLANTABLE CARDIAC MONITOR IN DIAGNOSING CARDIAC ARRHYTHMIAS: A PROSPECTIVE RANDOMIZED CLINICAL TRIAL COMPARING REVEAL LINQ TRURHYTHMTM VERSUS CONFIRM RX SHARPSENSETM
Authors: Miki Yokokawa, Randy Ip, Ali Sheikh, Mark Castellani, John Ip
Journal: Journal of the American College of Cardiology (2020)
Clinical results of recombinant adenoviral human <i>p53</i> gene in treatment of malignant pleural effusions caused by advanced lung cancers.
Authors: Yong He
Journal: Journal of Clinical Oncology (2013)

e19026 Background: Management of the malignant pleural effusion caused by advanced or recurrent lung cancer is a big challenge for clinicians due to multiple reasons: patients’ poor conditions, resistance to chemo- or radio-therapy, intolerance to an aggressive treatment, et al. This report presents a new safe treatment for controlling this type of tough conditions. Methods: Fifty-six patients, 39 males and 17 females with an average age of 64.2 years old were included in this study. All these patients had either a lung cancer in advanced stage or a recurrent cancer after a radical tumorectomy, with malignant pleural effusion. After draining most of the effusion fluid, the patients received intra-cavity infusion of rAed-p53 once per week for 4 weeks, at dose of 2×10 12 viral particles (VP) diluted into 300 ml of saline solution. The complete response is defined as the complete disappearance of pleural or peritoneal fluid and negative cytologic findings for &gt;4 weeks, and the partial response is defined as a decrease over 50% of the fluid without the need of drainage and negative cytologic findings for &gt;4 weeks. Results: Participants were followed up for a median time of 15 month. Fifty patients (26.8%) achieved a complete response (CR) and 23 (41.1%) achieved a partial response (PR). The overall response rate is 67.9%. Patients’ quality of life, assessed by using Karnofsky performance scale (KPS) scores, was improved by an average of 27.2. The one-year of overall survival rate was 48.2% with a median survival time of 11.0 months. There were no serious side effects observed except for self-limited fever found in 82.6% of the cases. Conclusions: Intra-cavity infusion of rAd-p53 is a safe and effective method for controlling the malignant pleural effusion for patients with advanced lung cancer and in a poor condition, especially for those who can’t tolerate the standard treatments.
EVIDENCE OF LEAD PERFORATION ON ELECTROCARDIOGRAM-GATED COMPUTED TOMOGRAPHY MAY PREDICT RISK OF TAMPONADE AND NEED FOR CARDIAC SURGERY IN PATIENTS UNDERGOING TRANSVENOUS LEAD EXTRACTION
Authors: Andrew Nickel, Jamaluddin Moloo, Muhammad Aftab, Ryan Aleong, Matthew Zipse
Journal: Journal of the American College of Cardiology (2020)
Dose- and time-intensified ABVD without radiotherapy (RT) for advanced-stage Hodgkin lymphoma (HL) with mediastinal bulky disease (MBD).
Authors: Gaetano Corazzelli, Filippo Russo, Ferdinando Frigeri, Francesco Volzone, Gaetana Capobianco, Manuela Arcamone, Emanuela Morelli, Cristina Becchimanzi, Giampaolo Marcacci, Rosaria De Filippi, Mariangela Saggese, Antonio Pinto
Journal: Journal of Clinical Oncology (2012)

8066 Background: The role of consolidation RT on MBD after upfront chemotheraphy for advanced HL is debated, also given the supradditive iatrogenic risk. We present the results achieved in the subset of patients (pts) with MBD (max width &gt; 1/3 of thoracic diameter) accrued in a phase II study of an intensified ABVD program without RT. Methods: The current analysis derives from the final evaluation of our trial for advanced HL (stage IIXB-IV) conducted from 06/2004 to 03/2010 (Russo et al, ASH 2009 abst 715). Pts were scheduled to 6 cycles of a ‘time-densified’ ABVD (3-week intercycle, drugs on days 1 and 11) with the first 4 cycles being also ‘dose-intensified’: doxorubicin (ADM) 35 mg/m 2 , days 1 and 11 and G-CSF on days 6-8 and 17-19. Results: Of 82 accrued pts, 39 had BMD at presentation. Median age was 29yrs (r 16-58); male 46%; stage IIB 48%, III 8%, IV 43%; B-sympt 87%, E-disease 53%; IP Score ≥3 51%. All pts completed the intensified program. Median actual dose intensities for ADM, bleomycin, vinblastine and dacarbazine were 23.12, 6.69, 3.96 and 245 mg/week, respectively; the increase over conventional ABVD was 85% for ADM and averaged 32% for the other agents. PET2 negativity was achieved in 36/39 (92%; 95% CI 79-98), complete responses (CR) in 37/39 [94%; 95% CI 82-99]. At a median f.u. of 54 mo.s (r 20-91) all pts are alive with an event-free survival of 89% (95% CI, 80-98). Events were: &lt;CR (n=1, CS IVB), progression (n=1, CS IIIA), relapse [n=2; at 10 (CS IVA ) and 15 (CS IIB) months after treatment]; all these pts had isolated mediastinal recurrence. CTCAE v3.0 toxicity: Grade (G) 2 nail changes (31%), G2-G3 hemorrhoids (12%-3%), G3 infection (13%) and constipation (5%), G3-G4 stomatitis (7%-2%). No acute or delayed G3-G4 cardiac events, nor G3-G4 decline in pulmonary function (FEV 1, DL CO ,FEF25-75) were seen. Conclusions: Intensified ABVD can achieve PET2 negativity in a very high proportion of pts with MBD and ensure a long-term disease-free status even without RT. While results need confirmation on a randomized basis, the low mediastinal failure rate seems in line with recent suggestions that RT could be omitted in MBD when CR is achieved upon intensified chemotheraphy.
Phase Ib dose escalation study of oral quisinostat, a histone deacetylase inhibitor, in combination with bortezomib and dexamethasone for patients with relapsed multiple myeloma.
Authors: Xavier Leleu, Cyrille Touzeau, Lotfi Benboubker, Thierry Facon, Martine Delain, Nele Fourneau, Charles Phelps, Ann Forslund, Peter Hellemans, Johan Smit, Julie Badamo-Dotzis, Philippe Moreau
Journal: Journal of Clinical Oncology (2013)

8530 Background: Aggresome formation is a mechanism of resistance to agents (e.g., bortezomib) which block proteasome activity. HDACi (e.g., quisinostat) prevents aggresome formation by deacetylation of tubulin that allows the transport of unfolded proteins to lysosomes for degradation. Methods: Patients received quisinostat (Q) at escalated doses (6, 8, 10 and 12 mg) on days 1, 3, and 5 weekly, subcutaneous VELCADE (V) at 1.3 mg/m 2 on days 1, 4, 8, and 11 of a 3-week cycle, and oral dexamethasone (D) at 20 mg on the day of and the day after VELCADE dosing. The primary endpoint was the maximum tolerated dose (MTD) of Q in the combination (Q+V+D). The secondary endpoints included safety, overall response rate, and pharmacodynamic biomarkers. Results: Eighteen patients (3, 3, 6, and 6 in increasing Q doses) were enrolled: 56% male; median age = 69 (range 50-82) years; multiple myeloma stage: IA = 11% and IIIA = 89%; prior lines of therapy: 1 = 100%, 2 = 55.6%, and 3 = 11.1%; prior VELCADE treatment = 50%. At the highest dose (12 mg) 2 patients had dose-limiting toxicity, 1 with QTc prolongation and 1 with atrial fibrillation. The MTD was established at the 10 mg Q for the Q+V+D regimen. The most common adverse events (≥ 10% of patients) were diarrhea (39%), asthenia (33%), peripheral oedema (22%), nausea (17%), thrombocytopenia (17%), alopecia (11%), constipation (11%), and vomiting (11%); most were grade 2 or lower in toxicity. To date, 13 patients have discontinued treatment, of which 5 completed 11 cycles of treatment. The overall response rate was 87.5% (14/16, 95% CI: 61.7% to 98.5%), including 1 complete response, 2 very good partial response, and 11 partial responses. Most patients (9/11) showed a decrease in number of circulating multiple myeloma cells after 1 cycle. Two of 5 patients showed an increase in acetylated histone 3 from baseline as measured in peripheral blood mononuclear cells. Conclusions: The MTD is 10 mg quisinostat in combination with VELCADE and dexamethasone. The combination is active in the treatment of relapsed multiple myeloma and has an acceptable safety profile. Clinical trial information: NCT01464112.
Engineered Biomaterial Platforms to Study Fibrosis
Authors: Matthew D. Davidson, Jason A. Burdick, Rebecca G. Wells
Journal: Advanced Healthcare Materials (2020)

Abstract Many pathologic conditions lead to the development of tissue scarring and fibrosis, which are characterized by the accumulation of abnormal extracellular matrix (ECM) and changes in tissue mechanical properties. Cells within fibrotic tissues are exposed to dynamic microenvironments that may promote or prolong fibrosis, which makes it difficult to treat. Biomaterials have proved indispensable to better understand how cells sense their extracellular environment and are now being employed to study fibrosis in many tissues. As mechanical testing of tissues becomes more routine and biomaterial tools become more advanced, the impact of biophysical factors in fibrosis are beginning to be understood. Herein, fibrosis from a materials perspective is reviewed, including the role and mechanical properties of ECM components, the spatiotemporal mechanical changes that occur during fibrosis, current biomaterial systems to study fibrosis, and emerging biomaterial systems and tools that can further the understanding of fibrosis initiation and progression. This review concludes by highlighting considerations in promoting wide‐spread use of biomaterials for fibrosis investigations and by suggesting future in vivo studies that it is hoped will inspire the development of even more advanced biomaterial systems.