tbuckley/cabot-search huggingface dataset:
LBA25 Final overall survival (OS) analysis from ARCHES: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC)
Authors: A.J. Armstrong, T. Iguchi, A.A. Azad, R.Z. Szmulewitz, J. Holzbeierlein, A. Villers, A. Alcaraz, B.Y. Alekseev, N.D. Shore, D.P. Petrylak, B. Rosbrook, F. Zohren, S. Yamada, G.P. Haas, A. Stenzl
Journal: Annals of Oncology (2021)
119O Event-free survival (EFS), overall survival (OS), and safety of adding veliparib (V) plus carboplatin (Cb) or carboplatin alone to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) after ≥4 years of follow-up: BrighTNess, a randomized phase III trial
Authors: S. Loibl, W. Sikov, J. Huober, H.S. Rugo, N. Wolmark, J. O'Shaughnessy, D. Maag, M. Untch, M. Golshan, J. Ponce Lorenzo, O. Metzger, M. Dunbar, W.F. Symmans, C. Geyer
Journal: Annals of Oncology (2021)
An <i>in vivo</i> model of postinflammatory hyperpigmentation and erythema: clinical, colorimetric and molecular characteristics*
Authors: G. Vellaichamy, I. Kohli, R. Zubair, C. Yin, T. Braunberger, A.F. Nahhas, C. Nicholson, T.F. Mohammad, P. Isedeh, A.B. Lyons, N. Nartker, M. Al‐Jamal, M. Matsui, N. Karaman‐Jurukovska, L. Zhou, H.W. Lim, Q.‐S. Mi, I.H. Hamzavi
Journal: British Journal of Dermatology (2021)

Background Postinflammatory hyperpigmentation (PIH) is a common, acquired pigmentary disorder of the skin associated with significant quality-of-life impairment, especially in individuals with skin of colour. Current treatment for PIH is limited, largely due to a poor understanding of disease pathogenesis and the lack of a representative disease model. Objectives This study is intended to further develop, update and validate our previously designed in vivo model of acne-induced PIH/postinflammatory erythema (PIE) using different concentrations of trichloroacetic acid (TCA), a medium-depth chemical peel. Methods Twenty-nine patients with skin types II–VI and clinician-confirmed presence of two or more truncal acne pustules and PIH/PIE were included. On the basis of Investigator's Global Assessment (IGA), clinical polarized photography (CPP), colorimetry and Skindex, we experimentally determined an optimum TCA concentration and assessed our model's ability to exhibit a dose–response relationship between degree of inciting insult and severity of resulting pigmentation. We also performed differential microRNA profiling and pathway analysis to explore the potential of microRNAs as molecular adjuncts to our model. Results Application of TCA 30% produced lesions indistinguishable from acne-induced PIH and PIE lesions on the basis of colorimetry data without causing epidermal necrosis. Application of progressively increasing TCA doses from 20% to 30% resulted in concentration-dependent increases in CPP, IGA and colorimetry scores at all timepoints during the study. miRNA-31 and miRNA-23b may play a role in PIH pathogenesis, although further validation is required. Conclusions Our TCA-based in vivo model, using TCA concentrations between 20% and 30% with an optimum of 30%, enables the quantitative assessment of the pigmentary response to varying degrees of cutaneous inflammation in a fashion that mirrors natural acne-induced PIH and PIE.
1418P Chronological improvement in the survival of advanced gastric cancer patients in the past 15 years
Authors: T. Ogata, Y. Narita, R. Kumanishi, T. Nakazawa, Y. Matsubara, H. Kodama, A. Nakata, K. Honda, T. Masuishi, H. Bando, S. Kadowaki, M. Ando, S. Ito, M. Tajika, K. Muro
Journal: Annals of Oncology (2021)
Modelling trajectories of parentally reported and physician‐confirmed atopic dermatitis in a birth cohort study*
Authors: T. Nakamura, S. Haider, S. Fontanella, C.S. Murray, A. Simpson, A. Custovic
Journal: British Journal of Dermatology (2021)

In a population-based birth cohort, we aimed to identify longitudinal trajectories of atopic dermatitis (AD) during childhood using data from different sources (validated questionnaires and healthcare records). We investigated the impact of different AD definitions on such trajectories and their relationships with various risk factors.
429P Maintenance treatment with cetuximab versus observation in RAS wild-type metastatic colorectal cancer: First results of the randomized phase II TIME-PRODIGE28 UNICANCER study according to RAS/BRAF status
Authors: V. Boige, E. Francois, M. Ben Abdelghani, J.M. Phelip, V. Lebrun-Ly, L. Mineur, M.P. Galais, A.L. Villing, V. Hautefeuille, L. Miglianico, C. de la Fouchardiere, D. Genet, N. Levasseur, N. Lachaux, H. Blons, F. Castan, S. Gourgou, O. Bouche
Journal: Annals of Oncology (2021)
272P Outcomes of patients (pts) who had received prior platinum (PP) therapy in the phase III EMBRACA trial of talazoparib (TALA) vs physician’s choice of chemotherapy (PCT) in patients with germline BRCA1/2 mutated (gBRCA1/2mut) advanced breast cancer (ABC)
Authors: M. Martin, H.S. Rugo, S.A. Hurvitz, J. Ettl, H. Roche, K-H. Lee, A. Goodwin, T. Usari, S. Lanzalone, C.A. Guenzel, J. Blum, J.K. Litton
Journal: Annals of Oncology (2021)
Evaluating Approaches to Improve Equity in Critical Care Resource Allocation in the COVID-19 Pandemic
Authors: Katherine Ross-Driscoll, Gregory Esper, Kathy Kinlaw, Yi-Ting Hana Lee, Alanna A. Morris, David J. Murphy, Rebecca D. Pentz, Chad Robichaux, Gerard Vong, Kevin Wack, Neal W. Dickert
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
1804P Baseline mutational profiles of patients (pts) with carcinoma-of-unknown-primary-origin (CUP) enrolled onto CUPISCO
Authors: C.B. Westphalen, A. Karapetyan, A. Beringer, T. Bochtler, N. Chalabi, N. Cook, G. Duran-Pacheco, S. Golding, E. Höglander, F. Losa, L. Mileshkin, H. Moch, C. Pauli, J. Ross, E. Sokol, R. Tothill, A. Krämer
Journal: Annals of Oncology (2021)
Hyaluronan-induced alterations of the gut microbiome protects mice against <i>Citrobacter rodentium</i> infection and intestinal inflammation
Authors: Tangyou Mao, Chien-Wen Su, Qiaorong Ji, Chih-Yu Chen, Rongjun Wang, Deepak Vijaya Kumar, Jinggang Lan, Lefei Jiao, Hai Ning Shi
Journal: Gut Microbes (2021)

Hyaluronan is a glycosaminoglycan polymer that has been shown to play an important role in homeostasis of the gastrointestinal tract. However, its mechanistic significance in gastrointestinal epithelial barrier elements remain unexplored. Here, our results revealed that hyaluronan treatment resulted in significant changes in the gut microbiota in mice. To demonstrate the functional consequences of hyaluronan-treatment and hyaluronan-induced microbiota alterations, Citrobacter rodentium- and DSS-induced colitis models and microbiota transplantation approaches were utilized. We showed that hyaluronan alleviated intestinal inflammation in both pathogen and chemically induced intestinal mucosal damage. The protection in bacterial colitis was associated with enhanced C. rodentium clearance and alleviation of pathogen-induced gut dysbiosis. Microbiota transplantation experiments showed that the hyaluronan-altered microbiota is sufficient to confer protection against C. rodentium infection. Colonization with Akkermansia muciniphila, a commensal bacterium that is greatly enriched by hyaluronan treatment, alleviated C. rodentium-induced bacterial colitis in mice. Additionally, Akkermansia-induced protection was found to be associated with the induction of goblet cells and the production of mucins and epithelial antimicrobial peptides. Collectively, these results provide novel insights into the regulatory role of hyaluronan in modulating the gut microbiota and immunity in enteric infection and inflammation, with therapeutic potential for gut microbiome-targeted immunotherapy.
1618P Worsening of breast and cervical cancer stage at diagnosis due to COVID-19 pandemic
Authors: A.P. Messias, R.R.D.C.C. Bonadio, O.A.N. Moreira, L. Vecchi Leis, B. Zanin Orsi, D. Negrini Batista, L. Testa, M.D.P Estevez Diz
Journal: Annals of Oncology (2021)
Nodal Recurrence in Patients With Node-Positive Breast Cancer Treated With Sentinel Node Biopsy Alone After Neoadjuvant Chemotherapy—A Rare Event
Authors: Andrea V. Barrio, Giacomo Montagna, Anita Mamtani, Varadan Sevilimedu, Marcia Edelweiss, Deborah Capko, Hiram S. Cody, Mahmoud El-Tamer, Mary L. Gemignani, Alexandra Heerdt, Laurie Kirstein, Tracy-Ann Moo, Melissa Pilewskie, George Plitas, Virgilio Sacchini, Lisa Sclafani, Audree Tadros, Kimberly J. Van Zee, Monica Morrow
Journal: JAMA Oncology (2021)

Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach.To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery.From November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center.Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative.The primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC.Of 610 patients with cN1 breast cancer treated with NAC, 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. The median (IQR) age of these 234 patients was 49 (40-58) years; median tumor size was 3 cm; 144 (62%) were ERBB2 (formerly HER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC; 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences.This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.
586P Safety of tazemetostat (TAZ) in combination with abiraterone/prednisone (A/P) or enzalutamide (E) in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC)
Authors: W. Abida, N. Iannotti, E. Kocabas Argon, L. Appleman, N. Michaud, A. Rajarethinam, D. Adib, D.R. Saltzstein
Journal: Annals of Oncology (2021)
561TiP A phase I dose-escalation study of ZN-d5, an BCL-2 inhibitor with improved selectivity, in patients with advanced non-Hodgkin lymphoma (NHL) or acute myeloid leukemia (AML)
Authors: J.M. Zaucha, T. Fiorino, A. Kalro, H-J. Shin, N. Viiala, L. Torres, G. Gordon, R. Kirshoff, S. Lopez, L. Makris, C. Miller, S. Park, D. Voliotis
Journal: Annals of Oncology (2021)
LBA45 Primary data from DESTINY-Lung01: A phase II trial of trastuzumab deruxtecan (T-DXd) in patients (Pts) with HER2-mutated (HER2m) metastatic non-small cell lung cancer (NSCLC)
Authors: B.T. Li, E.F.F. Smit, Y. Goto, K. Nakagawa, H. Udagawa, J. Mazieres, M. Nagasaka, L. Bazhenova, A.N. Saltos, E. Felip, J.M. Pacheco, M. Pérol, L. Paz-Ares, K. Saxena, R. Shiga, Y. Cheng, S. Acharyya, J. Shahidi, D. Planchard, P.A. Jänne
Journal: Annals of Oncology (2021)
Effective therapy for AML with RUNX1 mutation by cotreatment with inhibitors of protein translation and BCL2
Authors: Christopher P. Mill, Warren Fiskus, Courtney D. DiNardo, Christine Birdwell, John A. Davis, Tapan M. Kadia, Koichi Takahashi, Nicholas Short, Naval Daver, Maro Ohanian, Gautam Borthakur, Steven M. Kornblau, Michael R. Green, Yuan Qi, Xiaoping Su, Joseph D. Khoury, Kapil N. Bhalla
Journal: Blood (2021)
LBA6 KRYSTAL-1: Adagrasib (MRTX849) as monotherapy or combined with cetuximab (Cetux) in patients (Pts) with colorectal cancer (CRC) harboring a KRASG12C mutation
Authors: J. Weiss, R.D. Yaeger, M.L. Johnson, A. Spira, S.J. Klempner, M.A. Barve, J.G. Christensen, A. Chi, H. Der-Torossian, K. Velastegui, T. Kheoh, S-H.I. Ou
Journal: Annals of Oncology (2021)
Continuous Glucose Monitoring and Glycemic Control in Patients With Type 2 Diabetes Treated With Basal Insulin—Reply
Authors: Thomas W. Martens, Roy W. Beck, Richard M. Bergenstal
Journal: JAMA (2021)

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Human selenium binding protein hSP56, a putative chemopreventive protein, binds selenium by a novel mechanism
Authors: Yuxun Wang, Arthur J. Sytkowski
Journal: Cancer Research (2004)

4054  Human selenium binding protein hSP56, a putative chemopreventive protein, binds selenium by a novel mechanism. Cumulative and comprehensive data from both clinical and epidemiological studies have demonstrated the beneficial effect of selenium as a nutritional supplement in reducing the risk of developing several forms of cancer including prostate cancer. A variety of selenium compounds have been shown to inhibit cancer cell growth or induce apoptosis in culture. However, the molecular targets and mechanisms of this anti-tumor activity of selenium compounds remain largely unknown. We have previously identified genes expressed differentially in human prostate cancer cells with different phenotypes in term of metastatic potential and hormone sensitivity. One of the genes, which encodes human selenium binding protein (hSP56), the human homologue of a rodent gene implicated in chemoresistance, is highly expressed in androgen-sensitive LNCaP cells but not in androgen-insensitive PC-3 cells. This expression in LNCaP cells is reversibly down-regulated by androgen in vitro (Yang, M. and A. J. Sytkowski, Cancer Research, 1998. 58:3150). hSP56 has been proposed to mediate the growth inhibitory action of selenium toward prostate cancer cells (Venkateswaran, V., L.H. Klotz, and N.E. Fleshner Cancer Research, 2002. 62:540). In the present study, we show that human selenium binding protein is synthesized by LNCaP cells as a 56 kDa polypeptide. This hSP56 protein contains selenium as covalently attached component. We demonstrated this by culturing LNCaP cells in the presence of radioactive 75Se and subsequently immunoprecipitating the labeled hSP56 protein with antibodies against hSP56 followed by SDS-PAGE and autoradiography. However, hSP56 is not a selenocysteine-containing protein. Although there is nucleotide sequence in the 3’ untranslated region of the hSP56 gene with suggestive of a selenocysteine insertion sequence (SECIS) characteristic of selenoproteins, we determined that it is not functional in directing selenocysteine insertion. In addition, we have developed an effective method combining isoelectric focusing and immunoblotting and have demonstrated the existence of two isoforms of hSP56 protein isolated from LNCaP cells. The data indicate that hSP56 protein employs a novel mechanism to bind selenium. Elucidation of the molecular mechanism of selenium binding and of the function of hSP56 protein will provide important insights into the chemopreventive action of selenium.
156P Impact of HER2 status (HER2-low versus HER2-0) on complete histologic response after neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC)
Authors: C. Domergue, E. Martin, C. Lemarié, P. Jézéquel, J-S. Frenel, P. Augereau, M. Campone, A. Patsouris
Journal: Annals of Oncology (2021)
Changes in healthy and unhealthy working-life expectancy over the period 2002–17: a population-based study in people aged 51–65 years in 14 OECD countries
Authors: Michaël Boissonneault, Paola Rios
Journal: The Lancet Healthy Longevity (2021)

BackgroundIn response to population ageing, most countries within the Organisation for Economic Co-operation and Development (OECD) are planning increases to their pension age. To ensure the effectiveness of such measures, scholars have advocated for continued monitoring of healthy working-life expectancy. However, estimates are limited to a few countries during limited periods of time. Our study aims to estimate healthy and unhealthy working-life expectancy in 14 OECD countries at three points in time between 2002 and 2017.MethodsIn this population-based study, we used cross-sectional data from nationally representative surveys on ageing that were representative of the population aged 51–65 years in England, the USA, and 11 European countries plus Israel. European countries, except for England, and Israel were divided into two groups according to their score on the Active Ageing Index (AAI). We estimated healthy and unhealthy working-life expectancy, defined as the number of years spent working in good or in poor health. Poor health was defined as the presence of at least one chronic disease. Sullivan's method was used to estimate expectancies.FindingsAmong men, healthy working-life expectancy increased in low-AAI countries (4·15 in 2002, 95% CI 4·01–4·30; vs 4·73 in 2017, 4·58–4·87; p<0·0001), but decreased in the USA (3·68 in 2002, 3·47–3·89; vs 3·21 in 2017, 3·03–3·38; p<0·0001). Among women, healthy working-life expectancy increased in England (3·55 in 2002, 3·39–3·71; vs 4·47 in 2017, 4·14–4·81; p<0·0001), high-AAI countries (4·16 in 2002, 4·02–4·30; vs 4·80 in 2017, 4·65–4·96; p<0·0001), and low-AAI countries (2·41 in 2002, 2·30–2·52; vs 4·00 in 2017, 3·88–4·12; p<0·0001). Unhealthy working life expectancy increased among men and women in all countries. In all countries, the greatest number of years spent unhealthy and working was among men and women with hypertension or arthritis.InterpretationAcross countries, increases in the total number of years spent working were systematically accompanied by increases in the number of years spent working with a chronic disease. The burden of chronic diseases will probably continue to increase among older workers as countries plan to further increase their pension ages, but prevention of hypertension and arthritis could mitigate this trend.FundingNetherlands Interdisciplinary Demographic Institute (NIDI-KNAW) and University of Groningen.
208P ARB: Phase II window of opportunity study of preoperative treatment with enzalutamide in ER+ve and TNBC
Authors: P. Schmid, P. Gomez-Pardo, D. Wheatley, P. Roy, P. Krabisch, M. Thill, S. Ledwidge, A. Thompson, E.J. Macaskill, N. Viehstädt, A. Purushotham, O. Gluz, A. Stefek, C. Ackerman, A. Prendergast, K. Mousa, L. Jones, G. Viale, J. Cortés, S. Kümmel
Journal: Annals of Oncology (2021)
Role of the pituitary in tumor promotion with ethinyl estradiol in rat liver
Authors: I P Hällström, D Liao, Y Assefaw-Redda, L C Ohlson, L Sahlin, P Eneroth, L Eriksson, J Gustafsson, A Blanck
Journal: Hepatology (1996)

Synthetic estrogens act as tumor promoters in rat liver. Because estrogen treatment markedly increases the secretion of pituitary prolactin, also shown to be a tumor promoter in rat liver, the possibility of a pituitary influence in estrogen promotion was investigated in Wistar rats. In diethylnitrosamine (DEN)–initiated hypophysectomized (hx) female rats, 24 weeks of ethinyl estradiol (EE) administration (500 microg/kg/d, intraperitoneally) did not increase the number of hepatocyte nodules and did not induce hepatocellular carcinoma (HCC) in a 2–year study. Very few placental forms of glutathione–S–transferase (GST–P)–positive foci were observed at the end of EE administration. Estrogen receptor (ER) messenger RNA (mRNA) levels in hx females were 20% of the levels in intact females. EE administration (range, 160–210 microg/kg/d, subcutaneous release pellets) to DEN–initiated intact males and females increased the number and size of hepatocyte foci. A significant increase in HCC frequency was observed in EE–treated females compared with females receiving sham–release pellets, and the latency period for HCC induction was decreased by EE in both males and females. Inhibition of prolactin (PRL) secretion by bromocriptine (Brc) (ParlodelLAR, slow intramuscular release vehicles) during EE treatment decreased the number of foci without affecting their size and markedly prolonged the latency period in both sexes. EE treatment also significantly increased the expression of c–myc, and c–jun, enhanced the levels of growth hormone receptor (GHr) mRNA in females and the levels of ER mRNA in males and “feminized” the expression of the GH–regulated genes cytochrome P450 (CYP), 2C11, CYP 2C12, and GHr in male liver. Brc administration decreased the mRNA levels of the female–predominant CYP 2C12 in EE–treated males but otherwise had no effects. In conclusion, a decreased promotive effect of EE was obtained by decreasing the PRL levels, indicating that estrogens exert at least part of their promotion effects indirectly, by increasing the levels of pituitary PRL.
1076P Real-world efficacy and safety data of immune checkpoint inhibitors in Turkish patients with metastatic melanoma: A Turkish oncology group study
Authors: M.A. Ozgun, I. Dogan, M. Karakurt Eryilmaz, A.P. Erdogan, M. Ayhan, E. Hafizoglu, P.K. Tolunay, E. Cavdar, G.T. Cevik, H. Demir, O. Dulgar, B. Yilmaz, E. Cakir, A. Gokyer, O.U. Unal, P. Perkin, T. Sakalar, A. Gulmez, E.S. Tasci, S. Lacin
Journal: Annals of Oncology (2021)