tbuckley/cabot-search huggingface dataset:
Results of an interim analysis of a multinational randomized, double-blind, phase III study in patients (pts) with previously treated metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo (CONFIRM 2)
Authors: C. Koehne, E. Bajetta, E. Lin, E. Van Cutsem, J. Hecht, J. Douillard, M. Moore, C. Germond, D. Laurent, C. Jacques
Journal: Journal of Clinical Oncology (2006)

3508 Background: PTK/ZK is a novel, oral, small molecule, antiangiogenic compound that inhibits tyrosine kinase signaling of all known vascular endothelial growth factor (VEGF) receptors. Methods: 855 pts were randomized to FOLFOX4 plus PTK/ZK (1250 mg, qd), or placebo. Eligibility included histologically or cytologically documented mCRC, pretreatment for metastatic disease with irinotecan/fluoropyrimidine-based chemotherapy, measurable disease by RECIST, PS of 0–2 and adequate organ and bone marrow function. The primary endpoint is overall survival (OS). Secondary endpoints included OS and PFS in high LDH pts (stratifiedbybaseline serum LDH levels &gt; 1.5 × ULN). Results: OS was 12.1 mo in the PTK/ZK arm and 11.8 mo in the placebo arm (HR: 0.94; p=0.511). A pre-planned triangular test suggested a low probability of demonstrating an improvement in OS at the final analysis (4Q 2006). The response rates (CR+PR) were 18.5% in the PTK/ZK arm, 17.5% in the placebo arm. PFS was significantly longer in the PTK/ZK arm (5.5 mo vs. 4.1 mo; HR: 0.83; p=0.026). LDH, usually a poor prognostic factor in mCRC, is predictive of the outcome in the PTK/ZK arm. Pts with high LDH showed a strong improvement in PFS when treated with PTK/ZK (5.6 mo vs. 3.8 mo; HR: 0.63; p&lt;0.001) and an improved OS (9.6 mo vs. 7.5 mo; HR: 0.78; p=0.10). Adverse events (AE) were similar to that of the CONFIRM 1 trial (ASCO 2005). Most frequent grade 3/4 AE associated with PTK/ZK were hypertension (PTK/ZK: 21%; placebo: 5%), diarrhea (16%; 8%), fatigue (14.5%; 6.9%), nausea (11%; 5%), vomiting (9%; 5%), dizziness (9%; 1%). AEs were generally reversible. Thrombotic and embolic events of all grades occurred in 6% (PTK/ZK) vs. 1% (placebo) and 4% vs. 1%, respectively. There was no increase in bowel perforations, hematological toxicities or peripheral neuropathy in the PTK/ZK arm. Conclusions: While the primary endpoint for OS was not met, PTK/ZK improves PFS significantly in the overall population, and shows strong activity in patients with high baseline serum LDH. [Table: see text]
Study on the effects of c-erbB-2-specific antisense oligonucleotides on c-erbB-2 overexpressing breast cancer cells
Authors: X. Liu, P. Fan, Z. Wu
Journal: Journal of Clinical Oncology (2006)

10724 Background: Overexpression of c-erbB2 oncoprotein was always correlated with bad prognostic. In this study, we will research on the effects of c-erbB-2-specific antisense oligonucleotides (ODNs) on c-erbB-2 expression, cell proliferation and apoptosis of c-erbB-2 over-expressing breast cancer TM40D cells, and to further study the effects of c-erbB-2-specific oligonucleotides on breast cancer xenografts in Balb/c mice. Methods: Balb/c mouse derived breast cancer cell line TM40D was incubated with liposome-mediated ODNs for 4 h and cultured for another 72 h, then the effects of ODNs on c-erbB-2 expression, cell proliferation and activation of apoptosis were examined by western blot, MTT assay and flow cytometry. Twenty-six mice with breast cancer xenografts were randomized into three groups—9 in control group, 9 in lipsome group and 8 in therapy group, which were injected hypodermically with 0.1 ml serum-free RPMI-1640 culture-medium, lipsome (10 ug/ml) solution, and the mixture of lipsome solution (10 ug/ml) and anti-sense ODN (1 uM) weekly for consecutive 6 weeks, respectively. After the therapy, the incidence of skin ulcer was recorded, the lumps were removed and weighted, and part of them were used for Flow Cytometry. Results: Western Blotting showed treatment of TM40D cells with c-erbB-2-specific antisense ODNs resulted in inhibition of c-erbB-2 expression. The effects of antisense ODNs on c-erbB-2 protein levels correlated with their effects on cell proliferation. MTT Assay showed antisense ODNs inhibited cell growth by about 50%. Flow cytometry analysis revealed that antisense ODNs increased cell apoptosis by38.5%, compared with cultured cells group 9.13% and liposome group 9.29%. The weight of lumps in the therapy group was significantly lower than that of in the other two groups. Flow Cytometry showed that in the therapy group the ratio of G0/G1 cells in cell cycles was 87.18%, which is higher compared with the other two and proliferation index was lower. Conclusions: Antisense ODNs reduced c-erbB-2 expression, inhibited cell proliferation and induced cell apoptosis. Anti-sense ODNs can inhibit the growth of c-erbB2-overexpressing breast cancer xenogarfts in Balb/c mice. No significant financial relationships to disclose.
TEXT-MINING IN ELECTRONIC HEALTHCARE RECORDS FOR EFFICIENT RECRUITMENT AND DATA-COLLECTION IN CARDIOVASCULAR TRIALS: A MULTICENTER VALIDATION STUDY
Authors: Wouter Van Dijk, Aernoud Fiolet, Ewoud Schuit, Arjan Sammani, Katrien Groenhof, Rieke van der Graaf, Martine de Vries, Marco Alings, Jeroen Schaap, Folkert Asselbergs, Diederick Grobbee, Rolf Groenwold, Arend Mosterd
Journal: Journal of the American College of Cardiology (2020)
EXTERNAL VALIDATION OF AN ARTIFICIAL INTELLIGENCE-GENERATED ALGORITHM TO DETECT LEFT VENTRICULAR SYSTOLIC DYSFUNCTION WITH ELECTROCARDIOGRAPHY IN THE POPULATION
Authors: Zachi Itzhak Attia, Ernest Diez Benavente, Andrew S. Tseng, David A. Leon, Jose Medina-Inojosa, Sofia Malyutina, Suraj Kapa, Henrik Schirmer, Alexander Kudryavtsev, Peter Noseworthy, Andrey Ryabikov, Rickey Carter, Pablo Perel, Paul Friedman, Francisco Lopez-Jimemez
Journal: Journal of the American College of Cardiology (2020)
The role of Ki-67 in molecular breast cancer classification.
Authors: George Stathopoulos, Nikolaos Malamos, Christos Markopoulos, Athanasios Polychronis, Sotirios Rigatos, A Yannopoulou, Maria Kaparelou, Athanasios Armakolas
Journal: Journal of Clinical Oncology (2012)

583 Background: The Ki-67 antigen was identified the involvement in early steps of polymerase I-dependent ribosomal RNA synthesis. Although it seems that the protein has an important function in cell division, its exact role is still obscure and there is little published work on its overall function. The aim of the present study is to evaluate the contribution of Ki-67 level in respect of tumor recurrence in molecular classified groups of breast cancer patients. Methods: Breast cancer tumor samples were examined for histological confirmation and for estrogen and progesterone receptors, c-erb-B2 expression, proliferation with Grade and Ki-67. Ki-67 was divided in percentage levels, up to 20 and higher than 20%. Immunohistochemistry and Fluorescence in situ hybridization is described for the results of ER, PR, c-erb-B2, Ki-67 biomarkers. Formaldehyde – fixed breast samples were paraffin wax embedded and processed for paraffin sections. The primary antibodies used were: The monoclinal antibody ID5 (M7047, Dakocytomation, Carpinteria, CA) for the detection of ER, the monoclonal anti-PR antibody 636 was used. For the detection of Ki-67 we used monoclonal mouse anti-human Ki-67 MIB-1. The patients molecular classification was Luminal A, Luminal B, Her-2 subtype and basal cell (triple negative). Results: 847 breast cancer patients were recruited. 291 were group as Luminal A, 228 as Luminal B, 221 Her-2 subtype and 107 triple negative. Follow-up was from 3 years to 15 years since diagnosis. It was found that in Luminal A patients, none had Ki-67 higher than 20% and the recurrence was in 10.65%. In Luminal B, the Ki-67 was higher than 20% in 61% of the patients and recurrence 23.68%. In Her-2 subtype &gt;20% Ki-67 was 78.94%, recurrence 17.19%. In triple negative &gt; 20% Ki-67 was in 68.75% and recurrence in 29.90% of the patients. Conclusions: The data presented here indicate that Ki-67 level may be considered as one of valuable biomarkers in breast cancer patients process and recurrence.
Review of end points of phase III clinical trials with combination chemotherapy regimens for non-small cell lung cancer evaluating importance of quality of life.
Authors: Kumar Prabhash, Ganesh Divekar, Minish Mahendra Jain, Bharatsinha Baburao Bhosale
Journal: Journal of Clinical Oncology (2013)

e19119 Background: Systemic combination chemotherapy is accepted as a standard of care for patients with advanced non-small cell lung cancer (NSCLC). Substantial similarities in terms of treatment efficacy and survival have emerged over the years between the different systemic chemotherapy regimens used. Quality of life (QOL) analysis will help to customize chemotherapy to improve outcome in NSCLC patients. Methods: Using PUBMED database, a review of randomized controlled phase III trials of advanced NSCLC published in last 5 years reporting comparative safety and efficacy between chemotherapeutic regimens as end points was conducted. An evaluation of end points, difference in efficacy endpoints, QOL analysis, and final conclusion was conducted. Results: The search criteria identified 51 trials (33,481 patients). Out of these 51 clinical trials, 16 trials showed difference in efficacy (13 survival endpoint, 1 ORR (objective response rate), 2 survival without grade 3/4 toxicity) and 11 trials used validated QOL instruments and were included for review. Two trials; one comparing pemetrexed/cisplatin with gemcitabine/cisplatin, and other comparing cisplatin/weekly vinoralbine with cisplatin/vinoralbine on day 1 and 8; showed difference with QOL; though not statistically significant. The QOL reporting/analysis techniques were heterogeneous. Two trials used QOL as primary endpoint. Safety reporting included percentage adverse events with treatment arms. Conclusions: Based on our review, it seems critical to have QOL as an endpoint while evaluating newer combination chemotherapeutic regimens for NSCLC. Secondly, it is unlikely that a major difference exists in the global QOL associated with standard chemotherapy regimens for NSCLC. An effort to have uniform QOL assessment across trials evaluating newer combination regimens for NSCLC will help to customize treatment.
IMPACT OF CORONARY ARTERY CALCIUM SCORING ON STATIN-ELIGIBILITY AND OUTCOMES IN WOMEN: THE CLARIFY STUDY
Authors: Sadeer G. Al-Kindi, Nour Tashtish, Imran Rashid, Varun Sundaram, David Zidar, Jared Durieux, Robert C. Gilkeson, Sanjay Rajagopalan
Journal: Journal of the American College of Cardiology (2020)
Angiopoietin-2 blockade ameliorates autoimmune neuroinflammation by inhibiting leukocyte recruitment into the CNS
Authors: Zhilin Li, Emilia A. Korhonen, Arianna Merlini, Judith Strauss, Eleonoora Wihuri, Harri Nurmi, Salli Antila, Jennifer Paech, Urban Deutsch, Britta Engelhardt, Sudhakar Chintharlapalli, Gou Young Koh, Alexander Flügel, Kari Alitalo
Journal: Journal of Clinical Investigation (2020)

Angiopoietin-2 (Ang2), a ligand of the endothelial Tie2 tyrosine kinase, is involved in vascular inflammation and leakage in critically ill patients. However, the role of Ang2 in demyelinating central nervous system (CNS) autoimmune diseases is unknown. Here, we report that Ang2 is critically involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis. Ang2 expression was induced in CNS autoimmunity, and transgenic mice overexpressing Ang2 specifically in endothelial cells (ECs) developed a significantly more severe EAE. In contrast, treatment with Ang2-blocking Abs ameliorated neuroinflammation and decreased spinal cord demyelination and leukocyte infiltration into the CNS. Similarly, Ang2-binding and Tie2-activating Ab attenuated the development of CNS autoimmune disease. Ang2 blockade inhibited expression of EC adhesion molecules, improved blood-brain barrier integrity, and decreased expression of genes involved in antigen presentation and proinflammatory responses of microglia and macrophages, which was accompanied by inhibition of α5β1 integrin activation in microglia. Taken together, our data suggest that Ang2 provides a target for increasing Tie2 activation in ECs and inhibiting proinflammatory polarization of CNS myeloid cells via α5β1 integrin in neuroinflammation. Thus, Ang2 targeting may serve as a therapeutic option for the treatment of CNS autoimmune disease.
SYSTEMIC VENOUS BAFFLE OBSTRUCTION AND LEAK INTERVENTION RESOLVES OXYGEN REQUIREMENT AND ASCITES IN TRANSPOSITION OF GREAT ARTERIES PALLIATED WITH MUSTARD PROCEDURE
Authors: Riyad Yazan Kherallah, Wilson Lam, Srinath Gowda, John Seger, Peter Ermis
Journal: Journal of the American College of Cardiology (2020)
Evidence of Concurrent Light Chain and Transthyretin Cardiac Amyloidosis in 2 Patients
Authors: Joseph P. Donnelly, Andrej Gabrovsek, Lidiya Sul, Claudiu Cotta, E. Rene Rodriguez, Carmela D. Tan, Mazen Hanna
Journal: JACC CardioOncology (2020)

Two distinct types of systemic amyloidosis, light chain (AL) and transthyretin (ATTR), account for >95% of diagnosed cardiac amyloidosis (CA) ([1][1]). AL arises from a clonal population of plasma cells that produce misfolded immunoglobulin light chains that aggregate in organs such as the heart,
FINDING UNDIAGNOSED PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA IN PRIMARY CARE USINGELECTRONIC HEALTH RECORDS
Authors: Latoya Williamson, Cezary Wojcik, Marshall Taunton, Kylie McElheran, William Howard, Dave Staszak, Samuel Gidding, Katherine Wilemon, Kelly Myers, Michael D. Shapiro
Journal: Journal of the American College of Cardiology (2020)
FONTAN PATIENTS WITH HEART FAILURE AND PRESERVED EJECTION FRACTION HAVE SIMILAR AFTERLOAD BUT MORE FAVORABLE VENTRICULO-ARTERIAL COUPLING THAN FONTAN PATIENTS WITH REDUCED EJECTION FRACTION
Authors: Shahryar Chowdhury, Eric Graham, Carolyn Taylor, Andrew Savage, Kimberly McHugh, Andrew Atz
Journal: Journal of the American College of Cardiology (2020)
MACROVASCULAR ABNORMALITIES AND FFRCT IN ISCHEMIA WITH NONOBSTRUCTIVE CORONARY ARTERIES (INOCA): THE CREDENCE TRIAL
Authors: Fay Lin, Alexander van Rosendael, Umberto Gianni, Wijnand Stuijfzand, Yao Lu, A. Maxim Bax, Emma J. Hollenberg, Inge J. van den Hoogen, Sara Tantawy, Jessica Pena, Subhi Al'Aref, Lohendran Baskaran, Simon Dunham, Kranthi Kolli, Hyuk-Jae Chang, Philippe Genereux, Gianluca Pontone, Jonathon Leipsic, Jeroen J. Bax, Daniel S. Berman, Jagat Narula, Paul Knaapen, James Min, Leslee J. Shaw
Journal: Journal of the American College of Cardiology (2020)
EFFECTS OF CLOSED LOOP STIMULATION VERSUS ACCELEROMETER RATE-ADAPTIVE PACING ON EXERCISE CAPACITY AND SUBJECTIVE SYMPTOMS IN PATIENTS WITH CHRONOTROPIC INCOMPETENCE AND HFREF IMPLANTED WITH CRT: THE CLASS TRIAL
Authors: Douglas Darden, Eric Adler, Maylene Alegre, Gregory Feld, Kurt S. Hoffmayer, Frederick T. Han, David Krummen, Farshad Raissi, Gordon Ho, Pam Taub, Marcus Urey, Ulrika Birgersdotter-Green, Jonathan Chong Hsu
Journal: Journal of the American College of Cardiology (2020)
PROGNOSIS OF HEART FAILURE FOLLOWING CARDIOTOXIC BREAST CANCER CHEMOTHERAPY: A RETROSPECTIVE MATCHED COHORT STUDY
Authors: Felicia Tai, Ruth Croxford, Peter Austin, Eitan Amir, Oscar Calvillo Argüelles, Heather Joan Ross, Douglas Lee, Paaladinesh Thavendiranathan, Husam Abdel-Qadir
Journal: Journal of the American College of Cardiology (2020)
A genetic variant of 5-hydroxytryptamine receptor 3C (HTR3C): A novel link to chemotherapy-induced side effects.
Authors: Tami Rubinek, Dorit Pud, Gil Har-Zahav, Zvi Symon, Yael Laitman, Ido Wolf
Journal: Journal of Clinical Oncology (2013)

9630 Background: Symptom clusters are defined as three or more concurrent symptoms that are related to each other. Clusters may stem from common physiological mechanisms and may better represent adverse effects to chemotherapy compared to individual symptoms. We aimed to identify association between the experience of symptom clusters and specific genetic alterations. Methods: Study population consisted of 108 breast cancer patients who received over two cycles of adjuvant doxorubicin and cyclophosphamide (AC) treatment at the oncology institute of the Sheba Medical Center. Participants completed the Memorial Symptom Assessment Scale, the Lee Fatigue Scale and the Center for Epidemiological Studies Depression Scale. Hierarchical cluster analysis was used to identify patients' subgroups based on their symptom experience. For the genetic analyses, DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) of candidate genes were tested using restriction endonuclease assays. Results: Two distinct subgroups were identified based on severity of fatigue, depression, nausea, and change in food tastes: "all high" (n=79) and "all low" (n=29) level of all symptoms. As patients did not have active cancer, symptoms were attributed solely to chemotherapy. A genetic variant of HTR3C (rs6766410) results in a substitution of asparagine to lysine (N163K) may be associated with nausea and vomiting. We tested the association between this variant and symptom score. 51 of 75 (68%) patients with high symptom score harbored the variant allele, compared to 13 of 28 (46%) of those with low symptom score (p=0.038). Conclusions: Analysis of genetic background of clusters, rather than for individual symptoms, represents a novel approach for the study of chemotherapy-induced side effects. This approach enabled the identification of HTR3C variant as a possible mediator of side effects following treatment with AC. Discovering the genetic basis of symptom clusters may lead to the development of novel diagnostic and therapeutic modalities able to improve symptom management. This may translate to improved outcome among chemotherapy-treated cancer patients.
The lifetime economic burden of inaccurate HER2 testing: Comparing false positive and false negative HER2+ early breast cancer patients in the United States.
Authors: Louis Garrison, Joseph Babigumira, Anthony Masaquel, Bruce Wang, Deepa Lalla, Melissa Brammer
Journal: Journal of Clinical Oncology (2013)

6626 Background: Trastuzumab is administered to patients with early breast cancer (EBC) whose tumors test positive for HER2 using IHC or FISH diagnostic tests. However, due to test characteristics and testing heterogeneity, patients may be misdiagnosed as false positive (FP) or false negative (FN). This analysis estimates the lifetime economic burden of inaccurate HER2 testing in the US. Methods: We developed a national-level economic model to estimate the impact on healthcare costs and quality-adjusted life years (QALYs) in both groups in 2012. The model estimates the expected number of FP and FN patients using literature-derived estimates of each test’s sensitivity, specificity, and utilization. Based on estimates from the literature, a FP patient would generate unneeded trastuzumab costs of about $56,000 and experience a chance (2.9%) of related cardiotoxicity; an FN patient would save $56,000 in trastuzumab costs, but lose 1.7 QALYs of life expectancy and face a greater likelihood of recurrence and associated costs ($42,000) to treat metastatic disease. A net monetary benefit approach (valuing healthy life years at $100,000) is used to compare the lifetime economic burden for FP and FN. Results: The estimated overall proportions of FP and FN are 2.8% and 2.2% of 227,000 EBC patients, resulting in about 6,400 and 5,000 women in each group, respectively. Overall, approximately 8600 QALYs would be lost among FN patients who do not receive trastuzumab. We estimate the incremental per-patient lifetime burden of an FP to be about $57,000, and for an FN to be about $118,000. The implied incremental loss to society for FPs is $362 million and for FNs is $596 million. Conclusions: Current testing practices and treatment patterns for HER2+ EBC patients result in misdiagnosis and non-optimal treatment in approximately 11,500 patients each year: the combined total economic loss to society is nearly $1 billion. The greater share of the loss is among FN patients who would have benefited from trastuzumab, but did not receive it. The significant annual burden of HER2 misdiagnosis suggests that substantial societal investments to improve HER2 test accuracy should be considered.
Can sexual dimorphism in rheumatoid arthritis be attributed to the different abundance of<i>Gardnerella</i>?
Authors: Dongsong Liu, Feng Zhang, Hong Cao, Xuesong Wang
Journal: Annals of the Rheumatic Diseases (2020)

Rheumatoid arthritis (RA) is a common chronic inflammatory joint disease that can cause recurrent attacks of joint pain and swelling. Progression of RA eventually causes joint destruction, ankylosis and deformity, which are associated with significant increases in socioeconomic costs and burdens.1 2 Epidemiological studies conducted worldwide have shown that women are more likely than men of the same age to develop RA, and that the prevalence increases with age. More importantly, relevant literature indicates that the prevalence of RA continues to increase among women.3 4 In addition, female patients experience more severe joint dysfunction compared with male patients.4 Emerging data clearly demonstrate that women with RA have a significantly worse functional status as measured by instruments such as the 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire and visual analogue scale.4 5 Consequently, an understanding of the causes of this sexual dimorphism may provide new insights and guidance for the development of interventions intended to reduce the incidence of RA.

Previously, this sexual dimorphism of RA has been explained in terms of genes located on the X and Y chromosomes, sex hormones and specific physiological and psychosocial conditions.4 However, the above perspectives were accompanied by corresponding limitations. Notably, most of the relevant literature tended to elaborate from the perspective of sex hormones. Those studies focused on the effects of sex …
Transurethral Resection of Bladder Tumour: The Neglected Procedure in the Technology Race in Bladder Cancer
Authors: Hugh Mostafid, Marko Babjuk, Bernard Bochner, Seth P. Lerner, Fred Witjes, Joan Palou, Morgan Roupret, Sharokh Shariat, Paolo Gontero, Bas van Rhijn, Richard Zigeuner, Richard Sylvester, Eva Comperat, Maximilian Burger, Bernard Malavaud, Mark Soloway, Stephen Williams, Peter Black, Siamak Daneshmand, Gary Steinberg, Maurizio Brausi, Jim Catto, Ashish M. Kamat
Journal: European Urology (2020)
Abstract 11946: Effect of Evolocumab on Non-high-density Lipoprotein Cholesterol and Apolipoprotein B Levels: An Analysis of Double-blind and Open-label Extension Studies
Authors: Peter P Toth, Steven R Jones, Maria Laura Monsalvo, Mary Elliott-Davey, J Antonio G Lopez, Maciej Banach
Journal: Circulation (2019)

Introduction: Dyslipidemia guidelines have recommended non-HDL-C and ApoB either as co-primary or secondary targets of therapy. Objective: To evaluate the effect of evolocumab on non-HDL-C and ApoB...