tbuckley/cabot-search huggingface dataset:
SPC2996—A Bcl-2 RNA antagonist being studied in chronic lymphocytic leukemia
Authors: B. J. Hansen, M. Westergaard, M. Frieden, H. F. Hansen, L. S. Kjaerulff, C. A. Thrue, M. H. Wissenbach, L. W. Dalby, P. Kearney, H. Oerum
Journal: Journal of Clinical Oncology (2006)

6610 Background: Bcl-2 protein is a critical regulator of programmed cell death and contributes to apoptosis resistance in many cancers, including chronic lymphocytic leukemia (CLL). The novel RNA antagonist, SPC2996, is a 16-mer oligonucleotide incorporating Locked Nucleic Acid (LNA) with unique high-affinity binding to Bcl-2 mRNA and enhanced resistance to nuclease digestion. We report the pharmacological properties of this new investigational drug and are currently evaluating clinical safety and initial efficacy in CLL patients. Methods: In vitro, the effects of SPC2996 on Bcl-2 mRNA and protein levels and phenotypic responses were evaluated in human cancer cell lines by quantitative polymerase chain reaction, Western blotting and biochemical assays. In vivo bio-distribution in rodents was assessed with tritium-labelled SPC2996 given intravenously. Anti-tumour efficacy was assessed in human prostate (PC3) and melanoma (518A2 and 607B) tumour cell line xenografts in immunodeficient mice. Preclinical toxicology and safety pharmacology were evaluated after intravenous treatment in rats and primates and tissue uptake measured by HPLC. Results: In vitro, low nanomolar concentrations of SPC2996 substantially reduced intracellular levels of Bcl-2 mRNA and protein and induced apoptosis in a dose-dependant manner. In vivo, systemically administered SPC2996 accumulated in liver, kidney, bone marrow, and lymph nodes. Repeated dosing at 10mg/kg inhibited growth of human xenografts in mice. Substantial down-regulation of Bcl-2 mRNA was observed in primate tissues after intravenous administration of SPC2996 at 3 and 6mg/kg. No acute toxicity was encountered on systemic bolus dosing of substantially higher doses in primates. An international phase I/II dose-escalating study in 42 patients with relapsed or refractory CLL is currently recruiting in the USA, UK, Denmark and France. Conclusions: SPC2996 is the first member of a new generation of specific RNA antagonising oligonucleotides with enhanced properties derived from LNA. SPC2996 has the potential to lower Bcl-2 levels in CLL cells without significant toxicity and with less frequent dosing than required with previous drugs. [Table: see text]
Aortic Stenosis and the Tyrosine Kinase Inhibitor Nilotinib in Chronic Myeloid Leukemia
Authors: Miguel Carracedo, Leif Stenke, Anders Franco-Cereceda, Magnus Bäck
Journal: JACC CardioOncology (2020)

A 61-year-old woman diagnosed with chronic myeloid leukemia (CML) (Sokal intermediate risk) was treated with the tyrosine kinase inhibitor (TKI) nilotinib 600 mg/day. The patient was a nonsmoker and had no cardiovascular history, diabetes, or other relevant diseases. Blood tests revealed
Effect of aprepitant on adherence to high-dose cisplatin-based chemotherapy.
Authors: Serge Makarenko, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

9078 Background: Treatment of locally advanced head and neck cancers (HNC) and gastroesophageal cancers (GEC) frequently consists of high-dose cisplatin, which is highly emetogenic. Our aims were to 1) explore the impact of aprepitant for improving adherence to cisplatin-based chemotherapy in HNC and GEC, 2) examine its effect on reducing chemotherapy-induced nausea and vomiting (CINV) and 3) determine if use of aprepitant changed after introduction of insurance coverage for this drug. Methods: Patients diagnosed with HNC or GEC in British Columbia, Canada from Jan 2008 and June 2011 and prescribed high-dose cisplatin were reviewed. Using regression models that adjusted for confounders, we evaluated the relationship between aprepitant use and treatment and outcome characteristics, such as number of chemotherapy cycles, prevalence of CINV, and recurrence and survival. Results: A total of 333 patients were identified: 162 HNC and 171 GEC patients of whom 80% were men, 44% were aged &gt;/=60 years, 35% were smokers, and 42% were alcohol users. Aprepitant was prescribed in 49%, nausea and vomiting occurred in 64 and 24%, respectively, and completion of all planned cisplatin was 52%. Younger patients (55 vs 41%, p=0.01) and those with less tumor burden (64 vs 38%, p&lt;0.01) were more likely to be given aprepitant. Individuals who received aprepitant were significantly less likely to experience CINV (p&lt;0.01). Use of aprepitant differed between HNC and GEC patients (p&lt;0.01); however, its use did not increase when insurance coverage of this agent was introduced (p=0.16). In multivariate analyses, aprepitant use was significantly associated with adherence to all planned cisplatin treatments (OR 2.33, 95% CI 1.27-4.25, p&lt;0.01). In Cox regression, completion of all cisplatin cycles was significantly correlated with a lower risk of recurrence (HR 0.56, 95%CI 0.32-0.97 p=0.04) and a trend towards decreased death (HR 0.56, 95%CI 0.31-1.10, p=0.10). Conclusions: Aprepitant was associated with a reduction in CINV in both HNC and GEC patients and correlated with better adherence to high-dose cisplatin-based chemotherapy. Individuals who completed all planned cisplatin had improved outcomes, specifically a lower risk of recurrence from HNC and GEC.
IMPACT OF TREATMENT STRATEGY FOLLOWING ACUTE MYOCARDIAL INFARCTION ON READMISSION RISK
Authors: Raunak M. Nair, Mouin S. Abdallah, Michael Joseph Johnson, Kathleen Kravitz, Moses Anabila, Jeevanantham Rajeswaran, Eugene Blackstone, A. Lincoff, Venu Menon, Samir Kapadia, Umesh Khot
Journal: Journal of the American College of Cardiology (2020)
IMPACT OF HIS BUNDLE PACING ON LEFT VENTRICULAR FUNCTION COMPARED TO RIGHT VENTRICULAR APICAL PACING: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Mohamed Elmassry, Wasawat Vutthikraivit, Saif El-Nawaa, Pattara Rattanawong, Pakpoom Tantrachoti, Haitham Mazek, Pablo Paz, M Rubayat Rahman, Barbara Mantilla, John Abdelmalek, Pooja Sethi
Journal: Journal of the American College of Cardiology (2020)
A randomized controlled trial of a smoking cessation smartphone application with a carbon monoxide checker
Authors: Katsunori Masaki, Hiroki Tateno, Akihiro Nomura, Tomoyasu Muto, Shin Suzuki, Kohta Satake, Eisuke Hida, Koichi Fukunaga
Journal: npj Digital Medicine (2020)

Evidence of the long-term efficacy of digital therapies for smoking cessation that include a smartphone application (app) is limited. In this multi-center randomized controlled trial, we tested the efficacy of a novel digital therapy for smoking cessation: the "CureApp Smoking Cessation (CASC)" system, including a CASC smartphone app, a web-based patient management PC software for primary physicians, and a mobile exhaled carbon monoxide (CO) checker. A total of 584 participants with nicotine dependence were recruited from October 2017 to January 2018, and allocated 1:1 to the CASC intervention group or the control group. Both groups received a standard smoking cessation treatment with pharmacotherapy and counseling for 12 weeks. Meanwhile, the intervention group used the CASC system, and the control group used a control-app without a mobile CO checker, each for 24 weeks. The primary outcome was the biochemically validated continuous abstinence rate (CAR) from weeks 9 to 24. The main secondary outcome was an extended CAR from weeks 9 to 52. Except for 12 participants who did not download or use the apps, 285 participants were assigned to the intervention group, and 287, to the control. CAR from weeks 9 to 24 in the intervention group was significantly higher than that in the control group (63.9% vs. 50.5%; odds ratio [OR], 1.73; 95% confidence interval [CI], 1.24 to 2.42; P = 0.001). The CAR from weeks 9 to 52 was also higher in the intervention group than that in the control group (52.3% vs. 41.5%; OR, 1.55; 95% CI, 1.11 to 2.16; P = 0.010). No specific adverse events caused by the CASC system were reported. Augmenting standard face-to-face counseling and pharmacotherapy with a novel smartphone app, the CASC system significantly improved long-term CARs compared to standard treatment and a minimally supportive control app.
CIRCULATING EXTRA-CELLULAR RNAS AND ATRIAL FIBRILLATION: DATA FROM THE TRACE-CORE COHORT
Authors: Khanh-Van Tran, Kahraman Tanriverdi, Darleen Lessard, Gerard P. Aurigemma, Catarina Kiefe, Jane Freedman, David McManus
Journal: Journal of the American College of Cardiology (2020)
Relevance of rise in CA15.3 during fulvestrant therapy in advanced breast cancer patients.
Authors: Amit Agrawal, B Balakrishnan, Kwok-Leung Cheung, John Forsyth Russell Robertson
Journal: Journal of Clinical Oncology (2013)

e11567 Background: Serum CA15.3 (assay for MUC1 mucin, a membrane glycoprotein of breast ductal epithelium) is elevated in 50-70% of patients with metastatic disease. Transient initial rise (i.e., spike) of CA15.3 due to partial agonistic or cytotoxic effects of tamoxifen and chemotherapy is known. We report differential expression of spike in ER+ breast cancer showing clinical benefit (CB) or progressive disease (PD) on fulvestrant therapy (250mg). Methods: Serial serum CA15.3 measured at therapy initiation (Rx), 1, 3, 6, 9, 12 months and at progression were correlated with clinical outcome (CB/PD). Results: 112 patients (median age=71.4 years) with DOR=10.7+ (median duration of response in months, range) showed 63%CB (DOR=19.2+, 7-120.8+; MBC=48, LAPC=23) and 37%PD (DOR=3, 1-6; MBC=38, LAPC=3). Conclusions: CA15.3 spike was a common feature during therapy regardless of baseline level or clinical outcome (2nd row). However, in those with abnormal baseline (3rd row), %rise was higher in CB than PD patients reflecting greater tumour lyses (and perhaps therapy effectiveness) suggesting continuing therapy beyond early months (1-2 months) even with rising CA15.3. However, on analysis of only patients with spike, the majority of either CB or PD (4th row) were patients with MBC (perhaps reflecting higher tumour load) but with much larger %change in PD. Therefore, though therapy may not be stopped at early rise of CA15.3 but additional interim imaging may be required in MBC patients. [Table: see text]
Positive Selection and Inactivation in the Vision and Hearing Genes of Cetaceans
Authors: Michael R McGowen, Georgia Tsagkogeorga, Joseph Williamson, Phillip A Morin, and Stephen J Rossiter
Journal: Molecular Biology and Evolution (2020)

The transition to an aquatic lifestyle in cetaceans (whales and dolphins) resulted in a radical transformation in their sensory systems. Toothed whales acquired specialized high-frequency hearing tied to the evolution of echolocation, whereas baleen whales evolved low-frequency hearing. More generally, all cetaceans show adaptations for hearing and seeing underwater. To determine the extent to which these phenotypic changes have been driven by molecular adaptation, we performed large-scale targeted sequence capture of 179 sensory genes across the Cetacea, incorporating up to 54 cetacean species from all major clades as well as their closest relatives, the hippopotamuses. We screened for positive selection in 167 loci related to vision and hearing and found that the diversification of cetaceans has been accompanied by pervasive molecular adaptations in both sets of genes, including several loci implicated in nonsyndromic hearing loss. Despite these findings, however, we found no direct evidence of positive selection at the base of odontocetes coinciding with the origin of echolocation, as found in studies examining fewer taxa. By using contingency tables incorporating taxon- and gene-based controls, we show that, although numbers of positively selected hearing and nonsyndromic hearing loss genes are disproportionately high in cetaceans, counts of vision genes do not differ significantly from expected values. Alongside these adaptive changes, we find increased evidence of pseudogenization of genes involved in cone-mediated vision in mysticetes and deep-diving odontocetes.
Integrative Analysis of Multi-omics Data Identified EGFR and PTGS2 as Key Nodes in a Gene Regulatory Network Related to Immune Phenotypes in Head and Neck Cancer
Authors: Bohai Feng, Ying Shen, Xavier Pastor Hostench, Matthias Bieg, Michaela Plath, Naveed Ishaque, Roland Eils, Kolja Freier, Wilko Weichert, Karim Zaoui, Jochen Hess
Journal: Clinical Cancer Research (2020)

Malignant progression exhibits a tightly orchestrated balance between immune effector response and tolerance. However, underlying molecular principles that drive the establishment and maintenance of the tumor immune phenotype remain to be elucidated.We trained a novel molecular classifier based on immune cell subsets related to programmed death-ligand 1 (PD-L1) and interferon γ (IFNγ) expression, which revealed distinct subgroups with higher (cluster A) or lower (subcluster B3) cytotoxic immune phenotypes. Integrative analysis of multi-omics data was conducted to identify differences in genetic and epigenetic landscapes as well as their impact on differentially expressed genes (DEG) among immune phenotypes. A prognostic gene signature for immune checkpoint inhibition (ICI) was established by a least absolute shrinkage and selection operator (LASSO)-Cox regression model.Mutational landscape analyses unraveled a higher frequency of CASP8 somatic mutations in subcluster A1, while subcluster B3 exhibited a characteristic pattern of copy-number alterations affecting chemokine signaling and immune effector response. The integrative multi-omics approach identified EGFR and PTGS2 as key nodes in a gene regulatory network related to the immune phenotype, and several DEGs related to the immune phenotypes were affected by EGFR inhibition in tumor cell lines. Finally, we established a prognostic gene signature by a LASSO-Cox regression model based on DEGs between nonprogressive disease and progressive disease subgroups for ICI.Our data highlight a complex interplay between genetic and epigenetic events in the establishment of the tumor immune phenotype and provide compelling experimental evidence that a patient with squamous cell carcinoma of the head and neck at higher risk for ICI treatment failure might benefit from a combination with EGFR inhibition.
LIFETIME BURDEN OF TRADITIONAL CARDIOVASCULAR DISEASE RISK FACTORS AND INCIDENCE OF CANCER: THE BOGALUSA HEART STUDY
Authors: Alexander C. Razavi, Tanika N. Kelly, Jiang He, Camilo Fernandez – Alonso, Tekada Ferguson, Xiaocheng Wu, Rupert Barshop, Lauren Maniscalco, Marie Krousel-Wood, Seamus P. Whelton, Roger S. Blumenthal, Lydia Bazzano
Journal: Journal of the American College of Cardiology (2020)
MORTALITY IN PATIENTS WITH PRE-OPERATIVE AND PERSISTENT POST-OPERATIVE PULMONARY HYPERTENSION UNDERGOING MITRAL VALVE SURGERY FOR MITRAL REGURGITATION
Authors: Daniel Shpilsky, Gabrielle Vanspeybroeck, Ann Canterbury, Adam Handen, Joao L. Cavalcante, Michael Genuardi, Stephen Chan
Journal: Journal of the American College of Cardiology (2020)
SEQUENCE VARIANTS IN TITIN CAUSING SPLICING DEFECTS AND CARDIOMYOPATHY: INSIGHTS FOR GENE BASED DIAGNOSIS AND NORMAL PHYSIOLOGY
Authors: Parth Patel, Kaoru Ito, Jon A.L. Willcox, Joshua M. Gorham, Steven DePalma, Lien Lam, Alireza Haghighi, Arun Sharma, Barbara McDonough, Renee Johnson, Diane Fatkin, Christine Seidman, Jonathan Seidman
Journal: Journal of the American College of Cardiology (2020)
Sex Ratios in Families with BRCA Mutations [4] (multiple letters)
Authors: Matthew E. Mealiffe, Miguel De La Hoya, Juan M. Fernández, Alicia Tosar, Javier Godino, Ana Sánchez De Abajo, José A. Vidart, Pedro Pérez-Segura, Eduardo Díaz-Rubio, Trinidad Caldés
Journal: JAMA (2003)
Impact of chemotherapy dose-related factors on survival in breast cancer patients treated with adjuvant anthracycline-based chemotherapy
Authors: I. Chirivella, B. Bermejo, A. Insa, A. Perez-Fidalgo, A. Magro, S. Rosello, E. Garcia-Garre, P. Martin, A. Bosch, A. Lluch
Journal: Journal of Clinical Oncology (2006)

668 Background: The relationship between chemotherapy (CT) dose intensity and patient (pt) outcome in the management of early stage breast cancer (EBC) is still controversial. Although randomised clinical trials have provided evidence that supports the delivery of full standard doses of CT on schedule, precise thresholds for CT dose-related factors and their impact on survival-related endpoints have not yet been fully defined. The objective of this project is to assess the impact of CT dose-related factors on event-free and overall survival in a large group of EBC pts treated with anthracycline-based chemotherapy. Methods: A total of 1056 EBC (stage I-II-IIIA) cases diagnosed and treated from January 1980 to December 2000 were retrospectively studied. All of them received adjuvant anthracycline non-taxanes-based CT. Consecutive charts from 793 pts that were fully completed were included in the analysis. Survival-related endpoints were analysed through Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards models. Results: With a median follow-up of 10.0 years, pts exposed to either &gt; 2 cycle-delay (delay at any cycle defined as ≥ 3 days vs. plan), or ≥ 15 day-delay across the whole CT regimen, or &lt; 95% relative dose intensity (RDI) showed significantly worse 10-year Event-Free Survival (EFS) and Overall Survival (OS) as compared to pts with no dose delay/reduction (data shown below). Controlling for age at diagnosis, disease stage, histological grade, menopausal status and year of treatment did not modify these results. Conclusions: Based on this preliminary analysis, CT dose delays and reductions in EBC pts treated with adjuvant anthracycline-based regimens have a significantly negative impact on EFS and OS. [Table: see text] No significant financial relationships to disclose.
Correlation between body mass index and clinical and pathologic characteristics of breast tumor intrinsic subtypes.
Authors: Murat Bas, Selim Yalcin, Samed Rahatli, Nadire Kucukoztas, Omer Dizdar, Ozden Altundag
Journal: Journal of Clinical Oncology (2013)

e11532 Background: In this study it is aimed to investigate the association between body mass index between the clinical and pathological characteristics of breast tumor intrinsic subtypes defined by ER, PR and HER-2 expression status. Methods: 885 breast cancer patients followed-up at the Medical Oncology Departments of Baskent University Faculty of Medicine from 1983- 2012 were evaluated. In accordance with the criteria of the WHO, patients with BMI (kg/m²) &lt;18,5 were classified as underweight; 18.5-24.9 as normal; 25-29.9 as overweight, 30-34.9 as obese class I; between 35-39.9 as obese class II; and &gt; 40 as obese class III (morbid). Results: Median age of the 885 patients included in the study was 53.9. The number of pre-menopausals were 348 (43.2%). Average BMI was 27.2 kg/m². Compared to Luminal B and HER-2 positive groups, the rate of T1 tumors were significantly higher (p=0.002 and p=0.006) in Luminal A group. There was a statistically significant (p=0.046) difference in LVI rates between the groups, with the Luminal B group showing a higher rate of LVI. There was a statistically significant difference in PR positivity between groups as PR positivity was more frequent in the group with BMI between 30.0-34.99 kg/m² compared to the groups with BMI less than 25 kg/m² and BMI between 25.0-29.99 kg/m² (p=0.035 and p=0.003). There was a statistically significant difference in HER-2 between groups as the rate of HER-2 negatives was significantly higher, and the rate of HER-2 positives were significantly lower in the group with 30.0-34.99 kg/m², compared to the group with BMI less than 25 kg/m² (p=0.002 and p=0.048). Conclusions: Our results indicate the association between body mass index and clinical characteristics of breast tumor intrinsic subtypes. Further research is needed to explore biological role of BMI on tumor intrinsic subtypes.
THE EFFICACY AND SAFETY OF ALIROCUMAB IN PEDIATRIC PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: ODYSSEY KIDS
Authors: Stephen R. Daniels, Sonia Caprio, Umesh Chaudhari, Garen Manvelian, Marie Baccara-Dinet, Aurelie Brunet, Michel Scemama, Virginie Loizeau, Eric Bruckert
Journal: Journal of the American College of Cardiology (2020)
SAFETY AND EFFICACY OF NOVEL ORAL ANTICOAGULANTS COMPARED TO WARFARIN IN PATIENTS WITH CANCER AND ATRIAL FIBRILLATION: META-ANALYSIS
Authors: Bhavi Pandya, Srilekha Sridhara, Emrie Tomaiko, Abhishek Sawant, James Lafferty, John Corbelli, Hugh Calkins, Ashish Pershad
Journal: Journal of the American College of Cardiology (2020)
Adjuvant image guided (IGRT) intensity-modulated Arc radiotherapy for vulvar cancer.
Authors: Hanne From Mathiesen, Marie Louise Vorndran Coeln Banner-Voigt, Soeren Lassen, Mansoor Raza Mirza
Journal: Journal of Clinical Oncology (2013)

e16541 Background: A retrospective analysis to determine the efficacy and toxicity of PET-CT image guided intensity modulated arc radiotherapy (arctherapy) with concomitant weekly cisplatin as adjuvant treatment of vulvar cancer patients (pts) with high-risk of relapse after primary surgery. Methods: Pts were identified as high-risk of relapse after primary surgery (free-margins of vulvar tumor &lt;8mm; positive sentinel node/nodes). Pts were treated with radiation (RT) plus weekly cisplatin. All pts were planed by PET-CT scan. Target volumes were delineated together with onc-radiologist. The decision to irradiate vulva and/or unilateral/bilateral nodes was made independently. Principal of one-plus nodal region was applied. 46-50,7Gys were delivered in 23-27 daily fractions by arctherapy. Results: 25 consecutive pts (median age 64 years) were treated during 01.09.2008-30.09.2012. In the initial period IMRT was used (4 pts). Vulva was treated in all pts; unilateral nodal RT in 8 pts and bilateral nodal RT in 17 pts. No grade ≥2 toxicities were recorded. 24 pts are relapse-free with a median follow-up of 14.8 months. 1 pt had early relapse with later fatal outcome. Conclusions: Image guided arctherapy is highly effective and well tolerated. Further experience and long-term data with this technique is to be attained.
COMPARISON OF POST STENT OPTICAL COHERENCE TOMOGRAPHY FINDINGS AMONG THREE SUBTYPES OF CALCIFIED CULPRIT PLAQUES IN PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Akihiro Nakajima, Makoto Araki, Osamu Kurihara, Yoshiyasu Minami, Tsunenari Soeda, Taishi Yonetsu, Filippo Crea, Masamichi Takano, Takumi Higuma, Tsunekazu Kakuta, Tom Adriaenssens, Hang Lee, Sunao Nakamura, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2020)