tbuckley/cabot-search huggingface dataset:
Abstract ES8-3: Everything Comes at a Price - Toxicity, Cost and Adherence to Endocrine Therapy
Authors: DL Hershman
Journal: Cancer Research (2020)

Abstract Despite the proven efficacy of aromatase inhibitors (AIs) for the treatment of hormone-sensitive breast cancer (BC) adherence to therapy for the full duration of 5-years is suboptimal. Adherence is likely even lower for extended adjuvant therapy for up to 10-years. Issues related to non-adherence are increasingly important, as analyses from prospective randomized trials show compliance to endocrine therapy is associated with improved disease-free survival. The reasons for non-adherence to hormonal therapy are multifactorial. Barriers to compliance include patient, physician, medication and system related variables and poor compliance is usually associated with a combination of these factors. Characteristics associated with non-adherence include very high and low age, minority race, being single, increased number of comorbidities, lack of knowledge about efficacy of AI therapy, history of non-adherence to other chronic medications, limited insurance status, and higher out of pocket costs. Side effects from hormonal therapy is the most common reason for early discontinuation. AI arthralgia has been estimated to affect 45-60% of patients, many of whom report severe or continuous pain. One study reported an overall AI discontinuation rate of 32.4% within 2 years due to adverse effects, 24.3% specifically due to musculoskeletal symptoms, which was the primary reason for discontinuation. There is no consensus on the best treatment for AI arthralgia. The most commonly used therapy is NSAIDs, although there are no formal data testing their efficacy for AI arthralgia, and they are associated with potentially severe adverse effects. Randomized controlled trials have shown benefits from exercise (aerobic and strength training exercises), acupuncture, omega-3-fatty acids and duloxetine compared to placebo for AI arthralgia. Studies have also demonstrated improvement in symptoms over time even among patients receiving placebo. Various educational interventions have also been studied to improve adherence. A systematic review of behavioral interventions to enhance adherence to hormone therapy found five articles that met inclusion criteria and none reported the interventions significantly enhanced adherence compared to usual care. All evaluated educational interventions with or without reminders or navigation. In addition, a multicenter randomized clinical trial of patients with early stage breast cancer on AI’s found that bi-weekly unidirectional text messages for 36 months focused on overcoming potential barriers to medication adherence did not result in improved adherence to hormonal therapy. It is likely that improving long-term adherence will likely require sustained behavioral interventions and support. Citation Format: DL Hershman. Everything Comes at a Price - Toxicity, Cost and Adherence to Endocrine Therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES8-3.
Frequency of food allergy in school‐aged children in eight European countries—The EuroPrevall‐iFAAM birth cohort
Authors: Linus Grabenhenrich, Valérie Trendelenburg, Johanna Bellach, Songül Yürek, Andreas Reich, Ana Fiandor, Daniela Rivero, Sigurveig Sigurdardottir, Michael Clausen, Nikolaos G. Papadopoulos, Paraskevi Xepapadaki, Aline B. Sprikkelman, Bianca Dontje, Graham Roberts, Kate Grimshaw, Marek L. Kowalski, Marcin Kurowski, Ruta Dubakiene, Odilija Rudzeviciene, Montserrat Fernández‐Rivas, Philip Couch, Serge A. Versteeg, Ronald van Ree, Clare Mills, Thomas Keil, Kirsten Beyer
Journal: Allergy (2020)

Abstract Background The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent‐reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. Methods A follow‐up assessment at age 6‐10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double‐blind, placebo‐controlled oral food challenges (DBPCFC). Results A total of 6105 children participated in this school‐age follow‐up (57.8% of 10 563 recruited at birth). For 982 of 6069 children (16.2%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face‐to‐face interviews and/or skin prick testing, 238 (10.4%) were eligible for a DBPCFC. Sixty‐three foods were challenge‐tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy‐one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4% (88 related to all 6105 participants of this follow‐up) and 3.8% (88 related to 2289 with completed eligibility assessment). Interpretation In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons.
NAD(P)H: Quinone oxidoreductase 1 (<i>NQO1</i>) C609T polymorphism and lung cancer risk: A meta-analysis.
Authors: Yuqing Lou, Rong Li, Liwen Xiong, Baohui Han
Journal: Journal of Clinical Oncology (2012)

1551 Background: No clear consensus has been reached on the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and lung cancer risk. We performed a meta-analysis to summarize the possible association. Methods: We conducted a computer retrieval of PUBMED and EMBASE databases prior to January 2012. References of retrieved articles were also screened. According to the inclusion criteria, 24 articles (31 studies) were finally included. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. Results: There was no statistical association between C609T polymorphism and lung cancer risk in overall, East Asians, African-Americans or Hispanics. In Caucasians, significant association was found in allele comparison model (T vs. C) (P=0.04, OR=1.09, 95%CI [1.00–1.19], P heterogeneity =0.24, fixed-effects model). In Hawaiians, significant association could be found in dominant genetic model ((TT+CT) vs. CC) (P=0.04, OR=0.52, 95%CI [0.28–0.96], fixed-effects model). In the subgroup of squamous cell carcinoma, a borderline significance could be found in the dominant genetic model ((TT+CT) vs. CC) (P=0.05, OR=1.20, 95%CI [1.00–1.43], P heterogeneity =0.65, fixed-effects model). Significant association could also be found in allele comparison (T vs. C) (P=0.03, OR=1.21, 95%CI [1.01–1.44], P heterogeneity =0.68, fixed-effects model). In the subgroup of small cell lung cancer risk, significant association were found in allele comparison (T vs. C) (P=0.03, OR=1.68, 95%CI [1.05–2.68], P heterogeneity =0.10, random-effects model) and in the homozygote comparison (TT vs. CC) (P=0.02, OR=2.79, 95%CI[1.14–6.85], P heterogeneity =0.72, fixed-effects model). No association was observed in adenocarcinoma subgroup. Conclusions: NQO1 C609T polymorphism might associate with lung cancer risk in Caucasians and Hawaiians. NQO1 C609T polymorphism might also associate with squamous cell carcinoma and small cell lung cancer risk.
Abstract ES12-1: Clinical indications of PARP1 inhibitors and other targets
Authors: ML Telli
Journal: Cancer Research (2020)

Abstract Two PARP1 inhibitors, olaparib and talazoparib, garnered regulatory approvals for the treatment of advanced HER2-negative breast cancer associated with a germline BRCA1 or BRCA2 mutation in 2018. The approvals were based on a prolongation of progression-free survival with PARP inhibitor monotherapy compared to non-DNA damaging single agent chemotherapy in the 1st - 4th line metastatic setting. While the availability of these therapies has increased therapeutic options for this group of patients, median progression-free survival ranged from 7 - 8.6 months and no overall survival advantage has been observed to date. While response rates with PARP inhibitor monotherapy are high, development of resistance remains a significant clinical problem. Further, how PARP inhibitor monotherapy compares with platinum-based chemotherapy in this group of patients has been unclear. The recently reported phase III BROCADE 3 clinical trial examining carboplatin and paclitaxel with the addition of veliparib or placebo added important insights. This was the first phase III trial in patients with advanced germline BRCA1 and BRCA2 mutation-associated HER2-negative breast cancer that examined the use of a PARP inhibitor combined with DNA damaging chemotherapy in the 1st-3rd line setting followed by blinded monotherapy after discontinuation of chemotherapy. The median progression-free survival was significantly prolonged with the addition of veliparib (14.5 versus 12.6 months) with 26% of patients in the veliparib arm remaining progression-free at 36 months. Median overall survival was 33.5 months in the veliparib arm compared to 28.2 months in placebo with 44% of patients in the placebo arm crossing over to receive veliparib after disease progression. While important differences exist between these three trials, BROCADE 3 has reported the longest progression-free and overall survival to date with PARP inhibitor therapy in advanced germline BRCA1 and BRCA2 mutation-associated breast cancer. Beyond BRCA1 and BRCA2, PARP inhibitors are also being investigated in homologous recombination deficient advanced breast cancer in a number of clinical trials. In the Talazoparib Beyond BRCA study, high clinical activity was noted in germline PALB2 mutation carriers. The Olaparib Expanded trial is ongoing. Citation Format: ML Telli. Clinical indications of PARP1 inhibitors and other targets [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES12-1.
Mitochondrial Determinants of Doxorubicin-Induced Cardiomyopathy
Authors: Kendall B. Wallace, Vilma A. Sardão, Paulo J. Oliveira
Journal: Circulation Research (2020)

Anthracycline-based chemotherapy can result in the development of a cumulative and progressively developing cardiomyopathy. Doxorubicin is one of the most highly prescribed anthracyclines in the United States due to its broad spectrum of therapeutic efficacy. Interference with different mitochondrial processes is chief among the molecular and cellular determinants of doxorubicin cardiotoxicity, contributing to the development of cardiomyopathy. The present review provides the basis for the involvement of mitochondrial toxicity in the different functional hallmarks of anthracycline toxicity. Our objective is to understand the molecular determinants of a progressive deterioration of functional integrity of mitochondria that establishes a historic record of past drug treatments (mitochondrial memory) and renders the cancer patient susceptible to subsequent regimens of drug therapy. We focus on the involvement of doxorubicin-induced mitochondrial oxidative stress, disruption of mitochondrial oxidative phosphorylation, and permeability transition, contributing to altered metabolic and redox circuits in cardiac cells, ultimately culminating in disturbances of autophagy/mitophagy fluxes and increased apoptosis. We also suggest some possible pharmacological and nonpharmacological interventions that can reduce mitochondrial damage. Understanding the key role of mitochondria in doxorubicin-induced cardiomyopathy is essential to reduce the barriers that so dramatically limit the clinical success of this essential anticancer chemotherapy.
Potential short-term outcome of an uncontrolled COVID-19 epidemic in Lombardy, Italy, February to March 2020
Authors: Giorgio Guzzetta, Piero Poletti, Marco Ajelli, Filippo Trentini, Valentina Marziano, Danilo Cereda, Marcello Tirani, Giulio Diurno, Annalisa Bodina, Antonio Barone, Lucia Crottogini, Maria Gramegna, Alessia Melegaro, Stefano Merler
Journal: Eurosurveillance (2020)

Sustained coronavirus disease (COVID-19) transmission is ongoing in Italy, with 7,375 reported cases and 366 deaths by 8 March 2020. We provide a model-based evaluation of patient records from Lombardy, predicting the impact of an uncontrolled epidemic on the healthcare system. It has the potential to cause more than 250,039 (95% credible interval (CrI): 147,717–459,890) cases within 3 weeks, including 37,194 (95% CrI: 22,250–67,632) patients requiring intensive care. Aggressive containment strategies are required.
Covid-19 in Critically Ill Patients in the Seattle Region — Case Series
Authors: Pavan K Bhatraju, Bijan J Ghassemieh, Michelle Nichols, Richard Kim, Keith R Jerome, Arun K Nalla, Alexander L Greninger, Sudhakar Pipavath, Mark M Wurfel, Laura Evans, Patricia A Kritek, T Eoin West, Andrew Luks, Anthony Gerbino, Chris R Dale, Jason D Goldman, Shane O'Mahony, Carmen Mikacenic
Journal: New England Journal of Medicine (2020)

Community transmission of coronavirus 2019 (Covid-19) was detected in the state of Washington in February 2020. We identified patients from nine Seattle-area hospitals who were admitted to the intensive care unit (ICU) with confirmed infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data were obtained through review of medical records. The data reported here are those available through March 23, 2020. Each patient had at least 14 days of follow-up. We identified 24 patients with confirmed Covid-19. The mean (±SD) age of the patients was 64±18 years, 63% were men, and symptoms began 7±4 days before admission. The most common symptoms were cough and shortness of breath; 50% of patients had fever on admission, and 58% had diabetes mellitus. All the patients were admitted for hypoxemic respiratory failure; 75% (18 patients) needed mechanical ventilation. Most of the patients (17) also had hypotension and needed vasopressors. No patient tested positive for influenza A, influenza B, or other respiratory viruses. Half the patients (12) died between ICU day 1 and day 18, including 4 patients who had a do-not-resuscitate order on admission. Of the 12 surviving patients, 5 were discharged home, 4 were discharged from the ICU but remained in the hospital, and 3 continued to receive mechanical ventilation in the ICU. During the first 3 weeks of the Covid-19 outbreak in the Seattle area, the most common reasons for admission to the ICU were hypoxemic respiratory failure leading to mechanical ventilation, hypotension requiring vasopressor treatment, or both. Mortality among these critically ill patients was high. (Funded by the National Institutes of Health.).
Abstract P6-10-29: Circular RNAs in exosomes derived from breast cancer: Promising biomarkers for diagnosis and prognosis of triple negative breast cancer (TNBC)
Authors: Sujin Yang, Jinhai Tang
Journal: Cancer Research (2020)

Abstract Background: With the recent development of transcriptome sequencing technology, circular RNAs (circRNAs) have attracted extensive attention from researchers. Exosomes are usually recognized as a type of membrane vesicles containing RNA (mRNA, miRNA, circRNAs and other non-coding RNAs), proteins and lipids, and may be used as promising biomarkers for disease diagnosis. Unfortunately, circRNAs still remains many action mechanisms of circRNAs cannot be understood completely in the process of tumor development. The study aims to explore novel circRNAs and their potential functions in the treatment and progonsis of TNBC.Materials &amp; methods: A combinative strategy of RNA-sequencing (RNA-seq) technique, RT-qPCR and bioinformatic analysis was employed to unearth the potential mechanism of differential circRNAs in serum-exosomes (n=20) and tissues (n=20) from TNBC patients.Results: Combination of the two datasets from differential circRNAs in serum-exosomes and tissues, the result showed that three circRNAs (has-circRNA-LPXN, has-circRNA-NUFIP2 and has-circRNA-HSDL2) were significantly differentially-expressed in both datasets. RT-qPCR used to verify these three circRNAs in cells and serum-exosomes also found has-circRNA-LPXN was down-regulated and has-circRNA-HSDL2 was up-regulated, which was valuable for breast cancer diagnosis by analyzing these circRNAs in serum-exosomes from BCa patients compared with healthy people. Conclusion: The expression levels of has-circRNA-LPXN and has-circRNA-HSDL2 were found significantly different both in serum-exosomes and tissues of TNBC and these circRNAs might function as competing endogenous RNAs and play vital roles in the development of TNBC. More importantly, we constructed two circRNAs-miRNAs networks and provided new insight into prognosis and therapy of TNBC from circRNAs in the serum-exosomes. Citation Format: Sujin Yang, Jinhai Tang. Circular RNAs in exosomes derived from breast cancer: Promising biomarkers for diagnosis and prognosis of triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-29.
Abstract P5-05-05: Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds
Authors: Benita S. Katzenellenbogen, Yvonne Ziegler, Mary J Laws, Valeria S. Guillen, SungHoon Kim, Parama Dey, Brandi P. Smith, Ping Gong, Noah Bindman, Yuechao Zhao, Kathryn Carlson, Mayuri A. Yasuda, Divya Singh, Zhong Li, Dorraya El-Ashry, Zeynep Madak-Erdogan, John A. Katzenellenbogen
Journal: Cancer Research (2020)

Abstract The transcription factor FOXM1 is up-regulated and overexpressed in aggressive, therapy-resistant forms of hormone receptor-positive and triple negative breast cancers, and is associated with less good patient survival. FOXM1 signaling is also a key driver in many other cancers. Here, we identify a new class of compounds effective in suppressing FOXM1 activity in breast cancers, and displaying good potency for antitumor efficacy. The compounds bind directly to FOXM1 and alter its proteolytic sensitivity, reduce the cellular level of FOXM1 protein by a proteasome-dependent process, and suppress breast cancer cell proliferation and cell cycle progression and increase apoptosis. RNA-seq and gene set enrichment analyses indicate that the compounds decrease expression of FOXM1-regulated genes and suppress gene ontologies under FOXM1 regulation. Several compounds have favorable pharmacokinetic properties and show good tumor suppression in preclinical breast tumor models. These compounds may be suitable for further clinical evaluation in targeting aggressive breast cancers driven by FOXM1. (Supported by Breast Cancer Research Foundation grant (BCRF-083 to BSK), The Julius and Mary Landfield Cancer Research Fund (to BSK), NIH grant R01 DK015556 (to JAK), NIH T32 GM070421 Fellowship (to VSG), Bankhead-Coley Foundation grant 09BW04 (to DEA), USDA award ILLU-698-909 and National Center for Supercomputing Applications Faculty Fellowship (to ZME), and UIUC Environmental Toxicology Scholarship (to BPS)). Citation Format: Benita S. Katzenellenbogen, Yvonne Ziegler, Mary J Laws, Valeria S. Guillen, SungHoon Kim, Parama Dey, Brandi P. Smith, Ping Gong, Noah Bindman, Yuechao Zhao, Kathryn Carlson, Mayuri A. Yasuda, Divya Singh, Zhong Li, Dorraya El-Ashry, Zeynep Madak-Erdogan, John A. Katzenellenbogen. Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-05.
Results of aggressive surgical treatment for the patients with huge hepatocellular carcinoma (≥ 10 cm in diameter)
Authors: Oleg Kotenko, Oleksander Korshak, Oleksii Popov, Oleksander Grinenko, Denis Fedorov, Andrii Husiev, Oleksander Ostapishen, Marat Grigorjan, Andrii Zhylenko, Nellya Ablaeva, Tetiana Terzova
Journal: International Journal of Surgery (2020)
Abstract P1-09-06: Metabolic coupling in phyllodes tumor of the breast and its correlation to tumor progression
Authors: Ji Shin Leee, Nah Ihm Kim, Min Ho Park
Journal: Cancer Research (2020)

Abstract Background: Markers of metabolic coupling have been associated with clinical outcomes in numerous human cancers, including breast cancer. Loss of caveolin-1(CAV1) in stromal cells and upregulation of monocarboxylate transporters (MCTs), especially MCT1 and MCT4, in both stromal and cancer cells have been identified as playing an important role in the metabolic coupling necessary for release and uptake of metabolites. However, this phenomenon has been rarely described in phyllodes tumors (PTs) of the breast. Materials and methods: One hundred-one PTs (60 benign, 26 borderline, and 15 malignant) and 9 breast tissues with no pathological lesions were analyzed. Automated immunohistochemical staining for CAV-1, MCT1, and MCT4 was performed using tissue microarray blocks, and their expressions were assessed in both stromal and epithelial components. Results: Compared with normal breast, CAV-1 expression in PTs showed a significant decrease in stromal component (P &amp;lt; 0.001). MCT1 expression was significantly increased in both epithelial and stromal components of PTs compared to normal breast (P &amp;lt; 0.001 and P &amp;lt; 0.001, respectively). Stromal MCT1 and MCT4 expression was different according to the tumor grade of PTs and stromal MCT1 expression tended to increase with increasing tumor grade (P &amp;lt; 0.001). Although not statistically significant, stromal CAV-1 expression tended to decrease with increasing PTs grade. The recurrence rate was higher in the stromal MCT1-positive groups (19.2%, 14/73) than in the stromal MCT1-negative groups (3.9%, 1/28) (P &amp;lt; 0.05). Conclusions: This result suggested that changes of CAV-1, MCT1, and MCT4 may be associated with tumorigenesis and progression of PTs of the breast. Keywords Phyllodes tumor, CAV-1, MCT 1, MCT4, Metabolic coupling. Citation Format: Ji Shin Leee, Nah Ihm Kim, Min Ho Park. Metabolic coupling in phyllodes tumor of the breast and its correlation to tumor progression [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-09-06.